Reporter Assay Screens For Protein Targets In Saccharomyces Cerevisiae

Hosted; Thomas J. ;   et al.

Patent Application Summary

U.S. patent application number 12/967320 was filed with the patent office on 2011-06-09 for reporter assay screens for protein targets in saccharomyces cerevisiae. Invention is credited to Marvin Bayne, Thomas J. Hosted, Scott Walker.

Application Number20110136128 12/967320
Document ID /
Family ID36206622
Filed Date2011-06-09
United States Patent Application 20110136128
Kind Code A1
Hosted; Thomas J. ;   et al. June 9, 2011
REPORTER ASSAY SCREENS FOR PROTEIN TARGETS IN SACCHAROMYCES CEREVISIAE

Abstract

The present invention comprises responsive promoters along with screening methods which make use of the promoters in order to identify anti-fungal substances.

Inventors: Hosted; Thomas J.; (Summit, NJ) ; Walker; Scott; (Basking Ridge, NJ) ; Bayne; Marvin; (Westfield, NJ)
Family ID: 36206622
Appl. No.: 12/967320
Filed: December 14, 2010
Related U.S. Patent Documents
Application Number Filing Date Patent Number
11226605 Sep 14, 2005 7872115
12967320
60609940 Sep 15, 2004
Current U.S. Class: 435/6.13 ; 435/254.11; 435/320.1; 536/24.1
Current CPC Class: C12Q 1/18 20130101; C12Q 2600/158 20130101; C12Q 1/6897 20130101; C07K 14/395 20130101
Class at Publication: 435/6.13 ; 536/24.1; 435/320.1; 435/254.11
International Class: C12Q 1/68 20060101 C12Q001/68; C07H 21/04 20060101 C07H021/04; C12N 15/63 20060101 C12N015/63; C12N 1/15 20060101 C12N001/15
Claims


1. An isolated hybrid polynucleotide comprising a member selected from the group consisting of: S. cerevisiae YOR387C Promoter, S. cerevisiae YMR175W Promoter, S. cerevisiae YFR026C Promoter, S. cerevisiae YJL153C Promoter, S. cerevisiae YPL033C Promoter, S. cerevisiae YOL058W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDR250C Promoter, S. cerevisiae YDR446W Promoter, S. cerevisiae YDR536W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDL243C Promoter S. cerevisiae YDR256C Promoter, S. cerevisiae YFL020C Promoter, S. cerevisiae YPL205C Promoter, S. cerevisiae YGL205W Promoter, S. cerevisiae YGL117W Promoter, S. cerevisiae YHR029C Promoter, S. cerevisiae YML116W Promoter S. cerevisiae YJR109C Promoter, S. cerevisiae YCL030C Promoter, S. cerevisiae YLR338W Promoter, S. cerevisiae YIL066W-A Promoter, S. cerevisiae YNL093W Promoter, S. cerevisiae YLR381W Promoter, S. cerevisiae YKL159C Promoter, S. cerevisiae YIL058W Promoter, S. cerevisiae YKR037C Promoter, S. cerevisiae YNL279W Promoter, S. cerevisiae YOR032C Promoter, S. cerevisiae YML058W Promoter, S. cerevisiae YMR303C Promoter, S. cerevisiae YJL153C Promoter S. cerevisiae YLR092W Promoter, S. cerevisiae YFL052W Promoter, S. cerevisiae YIR017C Promoter, S. cerevisiae YLL062C Promoter, S. cerevisiae YMR323W Promoter S. cerevisiae YPL171C Promoter, S. cerevisiae YER065C Promoter, S. cerevisiae YDR114C Promoter, S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter, S. cerevisiae YLL020C Promoter and S. cerevisiae YBL065W Promoter; operably linked to a reporter.

2. An isolated polynucleotide of claim 1 wherein said promoter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1-41 and 52-68; and/or the reporter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 42-51.

3. An isolated vector comprising a polynucleotide of claim 1.

4. An isolated host cell comprising a vector of claim 3.

5. An isolated plasmid polynucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 85-88.

6. A method for identifying a substance that inhibits fungal cell growth comprising: (a) introducing a hybrid comprising a promoter selected from the group consisting of S. cerevisiae YOR387C Promoter, S. cerevisiae YMR175W Promoter, S. cerevisiae YFR026C Promoter, S. cerevisiae YJL153C Promoter, S. cerevisiae YPL033C Promoter, S. cerevisiae YOL058W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDR250C Promoter, S. cerevisiae YDR446W Promoter, S. cerevisiae YDR536W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDL243C Promoter S. cerevisiae YDR256C Promoter, S. cerevisiae YFL020C Promoter, S. cerevisiae YPL205C Promoter, S. cerevisiae YGL205W Promoter, S. cerevisiae YGL117W Promoter, S. cerevisiae YHR029C Promoter, S. cerevisiae YML116W Promoter S. cerevisiae YJR109C Promoter, S. cerevisiae YCL030C Promoter, S. cerevisiae YLR338W Promoter, S. cerevisiae YIL066W-A Promoter, S. cerevisiae YNL093W Promoter, S. cerevisiae YLR381W Promoter, S. cerevisiae YKL159C Promoter, S. cerevisiae YIL058W Promoter, S. cerevisiae YKR037C Promoter, S. cerevisiae YNL279W Promoter, S. cerevisiae YOR032C Promoter, S. cerevisiae YML058W Promoter, S. cerevisiae YMR303C Promoter, S. cerevisiae YJL153C Promoter S. cerevisiae YLR092W Promoter, S. cerevisiae YFL052W Promoter, S. cerevisiae YIR017C Promoter, S. cerevisiae YLL062C Promoter, S. cerevisiae YMR323W Promoter, S. cerevisiae YPL171C Promoter, S. cerevisiae YER065C Promoter and S. cerevisiae YDR114C Promoter; operably linked to a reporter; into a suitable fungal cell; (b) contacting the cell with a substance to be tested for the ability to inhibit fungal cell growth; and (c) detecting expression driven by the promoter in the hybrid; wherein the substance is identified as a fungal growth inhibitor if the substance modulates expression from the promoter.

7. A method of claim 6 wherein the promoter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1-41 and 68.

8. A method of claim 6 further comprising a negative-control comprising: (i) introducing the hybrid into a suitable fungal cell; (ii) contacting the cell with a blank substance which is known to not modulate expression from the promoter in the hybrid; and (iii) detecting expression driven by the promoter in the hybrid; and (iv) comparing the expression level from the promoter in the cell contacted with the blank substance with the expression level from the promoter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

9. A method of claim 6 further comprising a positive-control comprising: (i) introducing the hybrid into a suitable fungal cell; (ii) contacting the cell with a positive-control which is known to modulate expression from the promoter in the hybrid; (iii) detecting expression driven by the promoter in the hybrid; and (iv) comparing the expression level from the promoter in the cell contacted with the positive-control substance with the expression level from the promoter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

10. A method for identifying a substance that inhibits fungal cell growth comprising: (a) introducing, into a suitable fungal cell, a first hybrid comprising a first promoter selected from the group consisting of: S. cerevisiae YOR387C Promoter, S. cerevisiae YMR175W Promoter, S. cerevisiae YFR026C Promoter, S. cerevisiae YJL153C Promoter, S. cerevisiae YPL033C Promoter, S. cerevisiae YOL058W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDR250C Promoter, S. cerevisiae YDR446W Promoter, S. cerevisiae YDR536W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDL243C Promoter S. cerevisiae YDR256C Promoter, S. cerevisiae YFL020C Promoter, S. cerevisiae YPL205C Promoter, S. cerevisiae YGL205W Promoter, S. cerevisiae YGL117W Promoter, S. cerevisiae YHR029C Promoter, S. cerevisiae YML116W Promoter S. cerevisiae YJR109C Promoter, S. cerevisiae YCL030C Promoter, S. cerevisiae YLR338W Promoter, S. cerevisiae YIL066W-A Promoter, S. cerevisiae YNL093W Promoter, S. cerevisiae YLR381W Promoter, S. cerevisiae YKL159C Promoter, S. cerevisiae YIL058W Promoter, S. cerevisiae YKR037C Promoter, S. cerevisiae YNL279W Promoter, S. cerevisiae YOR032C Promoter, S. cerevisiae YML058W Promoter, S. cerevisiae YMR303C Promoter, S. cerevisiae YJL153C Promoter S. cerevisiae YLR092W Promoter, S. cerevisiae YFL052W Promoter, S. cerevisiae YIR017C Promoter, S. cerevisiae YLL062C Promoter, S. cerevisiae YMR323W Promoter S. cerevisiae YPL171C Promoter, S. cerevisiae YER065C Promoter, S. cerevisiae YDR114C Promoter and S. cerevisiae YBL065W Promoter; operably linked to a first reporter; and a second hybrid comprising a second promoter selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter; operably linked to a second reporter; wherein said first and second reporters are different; (b) contacting the cell with a substance to be tested for the ability to inhibit fungal cell growth; and (c) detecting expression driven from the first and second promoters; wherein the substance is identified as a fungal growth inhibitor if the substance causes the first promoter expression level to increase or decrease in relation to the expression level from the second reporter.

11. The method of claim 10 further comprising a negative-control comprising: (i) introducing said first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a blank substance which is known to not modulate expression from the promoters in the hybrids; (iii) detecting expression driven by the promoters in the hybrids; and (iv) comparing the expression level from the first promoter in relation to the expression level from the second promoter in the cell contacted with the blank substance with the expression level from the first promoter in relation to the expression level from the second promoter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

12. The method of claim 10 further comprising a positive-control comprising: (i) introducing said first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a positive-control substance which is known to modulate expression from the promoters in the hybrids; (iii) detecting expression driven by the promoters in the hybrids; and (iv) comparing the expression level from the first promoter in relation to the expression level from the second promoter in the cell contacted with the positive-control substance with the expression level from the first promoter in relation to the expression level from the second promoter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

13. A method of claim 10 wherein the first promoter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1-41 and 68; the second promoter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 52-67; and/or the reporter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 42-51.

14. A method for determining whether a substance inhibits growth of a fungal cell comprising: (a) introducing a hybrid comprising a promoter selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter; operably linked to a reporter into a suitable fungal cell; (b) contacting the cell with a substance to be tested for the ability to inhibit growth of the cell; and (c) detecting signal from the reporter; wherein the substance is identified as a fungal growth inhibitor if the substance causes a reduction in the signal from the reporter.

15. The method of claim 14 further comprising a negative-control comprising: (i) introducing the hybrid into a suitable fungal cell; (ii) contacting the cell with a blank substance which is known to not inhibit fungal cell growth; (iii) detecting signal from the reporter in the hybrid; and (iv) comparing the signal from the reporter in the cell contacted with the blank substance with the signal from the reporter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

16. The method of claim 14 further comprising a positive-control comprising: (i) introducing the hybrid into a suitable fungal cell; (ii) contacting the cell with a positive-control substance which is known to inhibit fungal cell growth; (iii) detecting signal from the reporter in the hybrid; and (iv) comparing the signal from the reporter in the cell contacted with the positive-control substance with the signal from the reporter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

17. A method of claim 14 wherein the promoter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 52-67; and/or the reporter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 42-51.

18. A method for determining whether a substance inhibits growth of a fungal cell comprising: (a) introducing a first hybrid comprising a first promoter selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter; operably linked to a first reporter; and a second hybrid comprising a second promoter selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter; operably linked to a second reporter into a suitable fungal cell; wherein said first and second promoter are different and wherein said first and second reporter are different; (b) contacting the cell with a substance to be tested for the ability to inhibit growth of the cell; and (c) detecting signal from the reporters; wherein the substance is identified as a fungal growth inhibitor if the substance causes a reduction in the signal from both the first and second reporters.

19. The method of claim 18 further comprising a negative-control comprising: (i) introducing the first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a blank substance which is known to not inhibit fungal cell growth; (iii) detecting signal from first and second reporters in the hybrids; and (iv) comparing the signal from the first and second reporters in the cell contacted with the blank substance with the signal from the first and second reporters in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

20. The method of claim 18 further comprising a positive-control comprising: (i) introducing the first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a positive control substance which is known to inhibit fungal cell growth; (iii) detecting signal from first and second reporters in the hybrids; and (iv) comparing the signal from the first and second reporters in the cell contacted with the positive control substance with the signal from the first and second reporters in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

21. A method of claim 18 wherein said promoters comprise a nucleotide sequence selected from the group consisting of SEQ ID NOs: 52-67; and/or the reporter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 42-51.

22. A method for determining whether a substance inhibits growth of a malignant cell comprising (a) introducing, into a suitable fungal cell, a first hybrid comprising a first promoter selected from the group consisting of: S. cerevisiae YLR338W, S. cerevisiae YIL066W, S. cerevisiae YNL093W, S. cerevisiae YDR250C, S. cerevisiae YLR381W, S. cerevisiae YBL065W, S. cerevisiae YMR323W and S. cerevisiae YPL171C; operably linked to a first reporter; and a second hybrid comprising a second promoter selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter; operably linked to a second reporter; (b) contacting the cell with a substance to be tested for the ability to inhibit growth of a malignant cell; and (c) detecting expression driven by the first and second promoters; wherein the substance is identified as a malignant cell growth inhibitor if the substance causes the expression level from the first promoter to increase or decrease in relation to the expression level from the second promoter.

23. The method of claim 22 wherein the first promoter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 8, 22-25, 38, 39 and 68; and/or the second promoter comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 52-67.

24. The method of claim 22 further comprising a negative-control comprising: (i) introducing said first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a blank substance which is known to not modulate expression from the promoters in the hybrids; and (iii) detecting expression driven by the promoters in the hybrids; (iv) comparing the expression level from the first promoter in realtion to the expression level from the second promoter in the cell contacted with the blank substance with the expression level from the first promoter in realtion to the expression level from the second promoter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

25. The method of claim 22 further comprising a positive-control comprising: (i) introducing said first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a positive-control substance which is known to modulate expression from the promoters in the hybrids; (iii) detecting expression driven by the promoters in the hybrids; and (iv) comparing the expression level from the first promoter in realtion to the expression level from the second promoter in the cell contacted with the positive control substance with the expression level from the first promoter in realtion to the expression level from the second promoter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.
Description


[0001] The present application is a continuation of U.S. patent application Ser. No. 11/226,605; filed Sep. 14, 2005 which claims the benefit of U.S. provisional patent application No. 60/609,940; filed Sep. 15, 2004; each of which is herein incorporated by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to compositions and methods for screening for compounds which modulate the function of an essential gene, for example, in fungal cells.

BACKGROUND OF THE INVENTION

[0003] High throughput assays, for identifying candidate compounds which inhibit one or more target proteins in an organism, are most efficient when they include an easily identifiable signal for identifying compounds with the desired inhibitory activity. One such well known system utilizes a responsive promoter, which is activated by the inactivation of the target by a candidate compound, and which is fused to an easily identifiable reporter. When the target protein is inactivated by a candidate compound, the reporter is expressed and the corresponding compound is identified as inhibitory. Such responsive promoters can be identified simply by identifying promoters which are activated by the genetic activation or inactivation of a target gene of interest (e.g., by construction of a temperature-sensitive mutation in the gene).

[0004] Responsive promoter screening assays have been used to identify anti-fungal compounds such as azoles which inhibit the egosterol biosynthesis pathway. U.S. Pat. No. 5,527,687; Dixon et al., J. Steroid Biochem. Mol. Biol. 1997 June; 62(2-3):165-71. In addition, screens have been developed to screen for inhibitors of protein secretion, membrane stability, protein synthesis and cell wall integrity. Bianchi et al., Appl Environ. Microbiol. 1999 November; 65(11):5023-7; Alksne et al., Antimicrob. Agents Chemother. 2000 June; 44(6):1418-27; Shapiro et al., Antimicrob. Agents Chemother. 2002 August; 46(8):2490-7; Sun et al., J. Antibiot. (Tokyo). 2002; 55(3): 279-287. These screens are convenient for high-throughput assay systems requiring short incubation times, sub-lethal compound concentrations and the selective induction of the reporter fusion indicates that the compound is perturbing the pathway of interest. Fischer et al., Genome Res. 2004 January; 14(1):90-8.

[0005] Although some responsive promoters are known and they have been used to identify anti-microbial substances, there still exists a need in the art for the identification of new responsive promoters which may be used to identify other substances of clinical interest.

SUMMARY OF THE INVENTION

[0006] The present invention addresses the need in the art for additional responsive promoters for use in assays to identify novel anti-fungal and anti-cancer substances.

[0007] The present invention provides an isolated hybrid polynucleotide comprising a member selected from the group consisting of S. cerevisiae YOR387C Promoter, S. cerevisiae YMR175W Promoter, S. cerevisiae YFR026C Promoter, S. cerevisiae YJL153C Promoter, S. cerevisiae YPL033C Promoter, S. cerevisiae YOL058W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDR250C Promoter, S. cerevisiae YDR446W Promoter, S. cerevisiae YDR536W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDL243C Promoter S. cerevisiae YDR256C Promoter, S. cerevisiae YFL020C Promoter, S. cerevisiae YPL205C Promoter, S. cerevisiae YGL205W Promoter, S. cerevisiae YGL117W Promoter, S. cerevisiae YHR029C Promoter, S. cerevisiae YML116W Promoter S. cerevisiae YJR109C Promoter, S. cerevisiae YCL030C Promoter, S. cerevisiae YLR338W Promoter, S. cerevisiae YIL066W-A Promoter, S. cerevisiae YNL093W Promoter, S. cerevisiae YLR381W Promoter, S. cerevisiae YKL159C Promoter, S. cerevisiae YIL058W Promoter, S. cerevisiae YKR037C Promoter, S. cerevisiae YNL279W Promoter, S. cerevisiae YOR032C Promoter, S. cerevisiae YML058W Promoter, S. cerevisiae YMR303C Promoter, S. cerevisiae YJL153C Promoter S. cerevisiae YLR092W Promoter, S. cerevisiae YFL052W Promoter, S. cerevisiae YIR017C Promoter, S. cerevisiae YLL062C Promoter, S. cerevisiae YMR323W Promoter S. cerevisiae YPL171C Promoter, S. cerevisiae YER065C Promoter, S. cerevisiae YDR114C Promoter, S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter, S. cerevisiae YLL020C Promoter and S. cerevisiae YBL065W Promoter (e.g., SEQ ID NOs: 1-41, 52-68); optionally operably linked to a reporter (e.g., S. cerevisiae ADE2, S. cerevisiae LYS2, S. cerevisiae TRP1, S. cerevisiae LEU2, S. cerevisiae URA3, S. cerevisiae HIS3, Aequorea victoria GFP mutant 3, Renilla luciferase, Photinus pyralis luciferase, Photinus pyralis luciferase slk mutant, Vibrio fischeri luxA, Vibrio fischeri luxB, Vibrio fischeri luxC, Vibrio fischeri luxD, Vibrio fischeri luxE, Vibrio fischeri luxAB, Vibrio fischeri luxCDABE, Vibrio harveyi luxA, Vibrio harveyi luxB, Vibrio harveyi luxC, Vibrio harveyi luxD, Vibrio harveyi luxE, Vibrio harveyi luxAB, Vibrio harveyi luxCDABE, Photorhabdus luminscens LuxA, Photorhabdus luminscens LuxB, Photorhabdus luminscens LuxC, Photorhabdus luminscens LuxD, Photorhabdus luminscens LuxE, Photorhabdus luminscens LuxCDABE, E. coli lacZ, the Aequorea victoria Aequorin gene, KanMX, pat1, nat1, hph, CAT, Sh Ble, GUS, CYH2 or CAN1 (e.g., SEQ ID NOs: 42-51)). Also within the scope of the invention is an embodiment comprising one of the foregoing promoters, operably linked to a reporter with the proviso that the reporter is not the open reading frame that is naturally located downstream of the promoter in the S. cerevisiae genome. An embodiment of the invention comprises a vector comprising a promoter of the present invention or hybrid thereof along with a host cell comprising the vector. In another embodiment of the invention, the vector in the host cell is episomal or integrated into a chromosome of the host cell.

[0008] The present invention also provides the isolated plasmids pSPRT47; pSPRT50; pSPRT190 and pSPRT192 (SEQ ID NOs.:85-88).

[0009] The present invention also provides a method for identifying a substance that inhibits fungal cell growth comprising (a) introducing a hybrid comprising a promoter selected from the group consisting of S. cerevisiae YOR387C Promoter, S. cerevisiae YMR175W Promoter, S. cerevisiae YFR026C Promoter, S. cerevisiae YJL153C Promoter, S. cerevisiae YPL033C Promoter, S. cerevisiae YOL058W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDR250C Promoter, S. cerevisiae YDR446W Promoter, S. cerevisiae YDR536W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDL243C Promoter S. cerevisiae YDR256C Promoter, S. cerevisiae YFL020C Promoter, S. cerevisiae YPL205C Promoter, S. cerevisiae YGL205W Promoter, S. cerevisiae YGL117W Promoter, S. cerevisiae YHR029C Promoter, S. cerevisiae YML116W Promoter S. cerevisiae YJR109C Promoter, S. cerevisiae YCL030C Promoter, S. cerevisiae YLR338W Promoter, S. cerevisiae YIL066W-A Promoter, S. cerevisiae YNL093W Promoter, S. cerevisiae YLR381W Promoter, S. cerevisiae YKL159C Promoter, S. cerevisiae YIL058W Promoter, S. cerevisiae YKR037C Promoter, S. cerevisiae YNL279W Promoter, S. cerevisiae YOR032C Promoter, S. cerevisiae YML058W Promoter, S. cerevisiae YMR303C Promoter, S. cerevisiae YJL153C Promoter S. cerevisiae YLR092W Promoter, S. cerevisiae YFL052W Promoter, S. cerevisiae YIR017C Promoter, S. cerevisiae YLL062C Promoter, S. cerevisiae YMR323W Promoter S. cerevisiae YPL171C Promoter, S. cerevisiae YER065C Promoter, S. cerevisiae YDR114C Promoter and S. cerevisiae YBL065W Promoter (e.g., SEQ ID NOs: 1-41 or 68) operably linked to a reporter (e.g., S. cerevisiae ADE2, S. cerevisiae LYS2, S. cerevisiae TRP1, S. cerevisiae LEU2, S. cerevisiae URA3, S. cerevisiae HIS3, Aequorea victoria GFP mutant 3, Renilla luciferase, Photinus pyralis luciferase, Photinus pyralis luciferase slk mutant, Vibrio fischeri luxA, Vibrio fischeri luxB, Vibrio fischeri luxC, Vibrio fischeri luxD, Vibrio fischeri luxE, Vibrio fischeri luxAB, Vibrio fischeri luxCDABE, Vibrio harveyi luxA, Vibrio harveyi luxB, Vibrio harveyi luxC, Vibrio harveyi luxD, Vibrio harveyi luxE, Vibrio harveyi luxAB, Vibrio harveyi luxCDABE, Photorhabdus luminscens LuxA, Photorhabdus luminscens LuxB, Photorhabdus luminscens LuxC, Photorhabdus luminscens LuxD, Photorhabdus luminscens LuxE, Photorhabdus luminscens LuxCDABE, E. coli lacZ, the Aequorea victoria Aequorin gene, KanMX, pat1, nat1, hph, CAT, Sh Ble, GUS, CYH2 or CAN1 (e.g., SEQ ID NOs: 42-51)) into a suitable fungal cell (e.g., Absidia corymbifera; Absidia spp; Acremonium spp; Ajellomyces capsulatus; Ajellomyces dermatitidis; Alternaria spp; Aphanoascus fulvescens; Apophysomyces spp; Arthroderma benhamiae; Arthroderma fulvum; Arthroderma gypseum; Arthroderma incurvatum; Arthroderma otae; Arthroderma vanbreuseghemii; Aspergillus flavus; Aspergillus fumigatus; Aspergillus glaucus; Aspergillus nidulans; Aspergillus niger; Aspergillus oryzae; Aspergillus spp; Aspergillus sydowi; Aspergillus terreus; Aspergillus ustus; Aspergillus versicolor; Aureobasidium pullulans; Basidiomycetes; Beauveria spp; Bipolaris hawaiiensis; Bipolaris spicifera; Bipolaris spp; Bjerkandera adusta; Blastomyces dermatitidis; Blastoschizomyces capitatus; Candida albicans; Candida beigelii; Candida colluculosa; Candida dubliniensis; Candida dubliniensis; Candida famata; Candida famata; Candida glabrata; Candida guilliermondii; Candida haemulonii; Candida holmii; Candida inconspicua; Candida intermedia; Candida keyfrr; Candida krusei; Candida krusei; Candida lambica; Candida lipolytica; Candida lusitaniae; Candida maris; Candida melibiosica; Candida norvegensis; Candida parapsilosis; Candida parapsilosis; Candida pelliculosa; Candida pelliculosa; Candida pseudotropicalis; Candida pulcherrima; Candida rugosa; Candida sake; Candida sphaerica; Candida spp; Candida stellatoidea; Candida tropicalis; Candida tropicalis; Candida viswanathii; Candida zeylanoides; Chrysosporium spp; Cladophialophora bantiana; Cladophialophora carrionii; Cladosporium spp; Coccidioides immitis; Cokeromyces recurvatus; Coprinus spp; Cryptococcus albidus; Cryptococcus gattii; Cryptococcus laurentii; Cryptococcus neoformans; Cunninghamella bertholletiae; Cunninghamella spp; Curvularia lunata; Curvularia spp; Dekkera bruxellensis; Epidermophyton floccosum; Epidermophyton floccosum; Exophiala dermatitidis; Exophiala jeanselmei; Exophiala moniliae; Exserohilum rostratum; Filobasidiella neoformans; Fonsecaea pedrosoi; Fusarium dimerum; Fusarium moniliforme; Fusarium oxysporum; Fusarium proliferatum; Fusarium solani; Fusarium spp; Geotrichum candidum; Geotrichum spp; Histoplasma capsulatum; Hortaea werneckii; Issatschenkia orientalis; Kluveromyces lactis; Kluyveromyces marxianus; Madurella grisae; Malassezia furfur; Malassezia globosa; Malassezia obtusa; Malassezia pachydermatis; Malassezia restricta; Malassezia slooffiae; Malassezia sympodialis; Metarrhizium anisopliae; Microsporum audouinii; Microsporum canis; Microsporum fulvum; Microsporum gypseum; Microsporum persicolor; Mucor circinelloides; Mucor hiemalis; Mucor racemosus; Mucor rouxii; Mucor spp; Nattrassia mangiferae; Nectria haematococca; Onychocola canadensis; Paecilomyces lilacinus; Paecilomyces spp; Paecilomyces variotii; Paracoccidioides brasiliensis; Penicillium marneffei; Penicillium spp; Phialophora spp; Phialophora verrucosa; Phoma spp; Pichia anomala; Pichia etchellsii; Pichia guilliermondii; Pichia ohmeri; Pithomyces spp; Pneumocystis carinii; Pseudallescheria boydii; Ramichloridium obovoideum; Rhizomucor miehei; Rhizomucor pusillus; Rhizomucor spp; Rhizopus arrhizus; Rhizopus microsporus; Rhizopus oryzae; Rhizopus schipperae; Rhizopus spp; Rhodotorula mucilaginosa; Rhodotorula rubra; Rhodotorula spp; Saccharomyces cerevisiae; Saccharomyces spp; Sagrahamala spp; Saksenaea vasiformis; Scedosporium apiospermum; Scedosporium prolificans; Schizophyllum commune; Schizosaccharomyces pombe; Scopulariopsis brevicaulis; Scytalidium dimidiatum Ulocladium spp; Sporobolomyces spp; Sporothrix schenckii; Trichoderma spp; Trichophyton krajdenii; Trichophyton mentagrophytes; Trichophyton raubitschekii; Trichophyton rubrum; Trichophyton soudanense; Trichophyton spp; Trichophyton terrestre; Trichophyton tonsurans; Trichophyton verrucosum; Trichophyton violaceum; Trichosporon asahii; Trichosporon beigelii; Trichosporon capitatum; Trichosporon cutaneum; Trichosporon inkin; Trichosporon mucoides; Trichosporon spp; Tritirachium spp; Wangiella dermatitidis and Yarrowia lipolytica); (b) contacting the cell with a substance to be tested for the ability to inhibit fungal cell growth; (c) detecting expression driven by the promoter or signal from the reporter in the hybrid; (d) selecting the substance if it modulates expression from the promoter or signal from the reporter. In an embodiment of the invention, the method is carried out along with a negative-control comprising (i) introducing the hybrid into a suitable fungal cell; (ii) contacting the cell with a blank substance which is known to not modulate expression from the promoter or signal from the reporter in the hybrid; and (iii) detecting expression driven by the promoter or signal from the reporter in the hybrid; and (iv) comparing the expression level from the promoter or signal from the reporter in the cell contacted with the blank substance with the expression level from the promoter or the signal from the reporter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth. Embodiments of the invention also include methods wherein a positive-control is carried out comprising (i) introducing the hybrid into a suitable fungal cell; (ii) contacting the cell with a positive-control which is known to modulate expression from the promoter or signal from the reporter in the hybrid; (iii) detecting expression driven by the promoter or signal from the reporter in the hybrid; and (iv) comparing the expression level from the promoter or signal from the reporter in the cell contacted with the positive-control substance with the expression level from the promoter or signal from the reporter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

[0010] The present invention further comprises a method for identifying a substance that inhibits fungal cell growth comprising (a) introducing, into a suitable fungal cell (e.g., Absidia corymbifera; Absidia spp; Acremonium spp; Ajellomyces capsulatus; Ajellomyces dermatitidis; Alternaria spp; Aphanoascus fulvescens; Apophysomyces spp; Arthroderma benhamiae; Arthroderma falvum; Arthroderma gypseum; Arthroderma incurvatum; Arthroderma otae; Arthroderma vanbreuseghemii; Aspergillus flavus; Aspergillus fumigatus; Aspergillus glaucus; Aspergillus nidulans; Aspergillus niger; Aspergillus oryzae; Aspergillus spp; Aspergillus sydowi; Aspergillus terreus; Aspergillus ustus; Aspergillus versicolor; Aureobasidium pullulans; Basidiomycetes; Beauveria spp; Bipolaris hawaiiensis; Bipolaris spicifera; Bipolaris spp; Bjerkandera adusta; Blastomyces dermatitidis; Blastoschizomyces capitatus; Candida albicans; Candida beigelii; Candida colluculosa; Candida dubliniensis; Candida dubliniensis; Candida famata; Candida famata; Candida glabrata; Candida guilliermondii; Candida haemulonii; Candida holmii; Candida inconspicua; Candida intermedia; Candida keyfyr; Candida krusei; Candida krusei; Candida lambica; Candida lipolytica; Candida lusitaniae; Candida maris; Candida melibiosica; Candida norvegensis; Candida parapsilosis; Candida parapsilosis; Candida pelliculosa; Candida pelliculosa; Candida pseudotropicalis; Candida pulcherrima; Candida rugosa; Candida sake; Candida sphaerica; Candida spp; Candida stellatoidea; Candida tropicalis; Candida tropicalis; Candida viswanathii; Candida zeylanoides; Chrysosporium spp; Cladophialophora bantiana; Cladophialophora carrionii; Cladosporium spp; Coccidioides immitis; Cokeromyces recurvatus; Coprinus spp; Cryptococcus albidus; Cryptococcus gattii; Cryptococcus laurentii; Cryptococcus neoformans; Cunninghamella bertholletiae; Cunninghamella spp; Curvularia lunata; Curvularia spp; Dekkera bruxellensis; Epidermophyton floccosum; Epidermophyton floccosum; Exophiala dermatitidis; Exophiala jeanselmei; Exophiala moniliae; Exserohilum rostratum; Filobasidiella neoformans; Fonsecaea pedrosoi; Fusarium dimerum; Fusarium moniliforme; Fusarium oxysporum; Fusarium proliferatum; Fusarium solani; Fusarium spp; Geotrichum candidum; Geotrichum spp; Histoplasma capsulatum; Hortaea werneckii; Issatschenkia orientalis; Kluveromyces lactis; Kluyveromyces marxianus; Madurella grisae; Malassezia furfur; Malassezia globosa; Malassezia obtusa; Malassezia pachydermatis; Malassezia restricta; Malassezia slooffiae; Malassezia sympodialis; Metarrhizium anisopliae; Microsporum audouinii; Microsporum canis; Microsporum fulvum; Microsporum gypseum; Microsporum persicolor; Mucor circinelloides; Mucor hiemalis; Mucor racemosus; Mucor rouxii; Mucor spp; Nattrassia mangiferae; Nectria haematococca; Onychocola canadensis; Paecilomyces lilacinus; Paecilomyces spp; Paecilomyces variotii; Paracoccidioides brasiliensis; Penicillium marneffei; Penicillium spp; Phialophora spp; Phialophora verrucosa; Phoma spp; Pichia anomala; Pichia etchellsii; Pichia guilliermondii; Pichia ohmeri; Pithomyces spp; Pneumocystis carinii; Pseudallescheria boydii; Ramichloridium obovoideum; Rhizomucor miehei; Rhizomucor pusillus; Rhizomucor spp; Rhizopus arrhizus; Rhizopus microsporus; Rhizopus oryzae; Rhizopus schipperae; Rhizopus spp; Rhodotorula mucilaginosa; Rhodotorula rubra; Rhodotorula spp; Saccharomyces cerevisiae; Saccharomyces spp; Sagrahamala spp; Saksenaea vasiformis; Scedosporium apiospermum; Scedosporium prolificans; Schizophyllum commune; Schizosaccharomyces pombe; Scopulariopsis brevicaulis; Scytalidium dimidiatum Ulocladium spp; Sporobolomyces spp; Sporothrix schenckii; Trichoderma spp; Trichophyton krajdenii; Trichophyton mentagrophytes; Trichophyton raubitschekii; Trichophyton rubrum; Trichophyton soudanense; Trichophyton spp; Trichophyton terrestre; Trichophyton tonsurans; Trichophyton verrucosum; Trichophyton violaceum; Trichosporon asahii; Trichosporon beigelii; Trichosporon capitatum; Trichosporon cutaneum; Trichosporon inkin; Trichosporon mucoides; Trichosporon spp; Tritirachium spp; Wangiella dermatitidis or Yarrowia lipolytica), a first hybrid comprising a first promoter selected from the group consisting of S. cerevisiae YOR387C Promoter, S. cerevisiae YMR175W Promoter, S. cerevisiae YFR026C Promoter, S. cerevisiae YJL153C Promoter, S. cerevisiae YPL033C Promoter, S. cerevisiae YOL058W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDR250C Promoter, S. cerevisiae YDR446W Promoter, S. cerevisiae YDR536W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDL243C Promoter S. cerevisiae YDR256C Promoter, S. cerevisiae YFL020C Promoter, S. cerevisiae YPL205C Promoter, S. cerevisiae YGL205W Promoter, S. cerevisiae YGL117W Promoter, S. cerevisiae YHR029C Promoter, S. cerevisiae YML116W Promoter S. cerevisiae YJR109C Promoter, S. cerevisiae YCL030C Promoter, S. cerevisiae YLR338W Promoter, S. cerevisiae YIL066W-A Promoter, S. cerevisiae YNL093W Promoter, S. cerevisiae YLR381W Promoter, S. cerevisiae YKL159C Promoter, S. cerevisiae YIL058W Promoter, S. cerevisiae YKR037C Promoter, S. cerevisiae YNL279W Promoter, S. cerevisiae YOR032C Promoter, S. cerevisiae YML058W Promoter, S. cerevisiae YMR303C Promoter, S. cerevisiae YJL153C Promoter S. cerevisiae YLR092W Promoter, S. cerevisiae YFL052W Promoter, S. cerevisiae YIR017C Promoter, S. cerevisiae YLL062C Promoter, S. cerevisiae YMR323W Promoter S. cerevisiae YPL171C Promoter, S. cerevisiae YER065C Promoter, S. cerevisiae YDR114C Promoter and S. cerevisiae YBL065W Promoter (e.g., SEQ ID NOs: 1-41 or 68); operably linked to a first reporter (e.g., S. cerevisiae ADE2, S. cerevisiae LYS2, S. cerevisiae TRP1, S. cerevisiae LEU2, S. cerevisiae URA3, S. cerevisiae HIS3, Aequorea victoria GFP mutant 3, Renilla luciferase, Photinus pyralis luciferase, Photinus pyralis luciferase slk mutant, Vibrio fischeri luxA, Vibrio fischeri luxB, Vibrio fischeri luxC, Vibrio fischeri luxD, Vibrio fischeri luxE, Vibrio fischeri luxAB, Vibrio fischeri luxCDABE, Vibrio harveyi luxA, Vibrio harveyi luxB, Vibrio harveyi luxC, Vibrio harveyi luxD, Vibrio harveyi luxE, Vibrio harveyi luxAB, Vibrio harveyi luxCDABE, Photorhabdus luminscens LuxA, Photorhabdus luminscens LuxB, Photorhabdus luminscens LuxC, Photorhabdus luminscens LuxD, Photorhabdus luminscens LuxE, Photorhabdus luminscens LuxCDABE, E. coli lacZ, the Aequorea victoria Aequorin gene, KanMX, pat1, nat1, hph, CAT, Sh Ble, GUS, CYH2 or CAN1 (e.g., SEQ ID NOs: 42-51)); and a second hybrid comprising a second promoter selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter (e.g., SEQ ID NOs: 52-67); operably linked to a second reporter (e.g., S. cerevisiae ADE2, S. cerevisiae LYS2, S. cerevisiae TRP1, S. cerevisiae LEU2, S. cerevisiae URA3, S. cerevisiae HIS3, Aequorea victoria GFP mutant 3, Renilla luciferase, Photinus pyralis luciferase, Photinus pyralis luciferase slk mutant, Vibrio fischeri luxA, Vibrio fischeri luxB, Vibrio fischeri luxC, Vibrio fischeri luxD, Vibrio fischeri luxE, Vibrio fischeri luxAB, Vibrio fischeri luxCDABE, Vibrio harveyi luxA, Vibrio harveyi luxB, Vibrio harveyi luxC, Vibrio harveyi luxD, Vibrio harveyi luxE, Vibrio harveyi luxAB, Vibrio harveyi luxCDABE, Photorhabdus luminscens LuxA, Photorhabdus luminscens LuxB, Photorhabdus luminscens LuxC, Photorhabdus luminscens LuxD, Photorhabdus luminscens LuxE, Photorhabdus luminscens LuxCDABE, E. coli lacZ, the Aequorea victoria Aequorin gene, KanMX, pat1, nat1, hph, CAT, Sh Ble, GUS, CYH2 and CAN1 (e.g., SEQ ID NOs: 42-51)); wherein said first and second reporters are different; (b) contacting the cell with a substance to be tested for the ability to inhibit fungal cell growth; (c) detecting expression driven by the first and second promoters or signal from the reporters; and (d) selecting the substance if it causes the first promoter expression level or reporter signal to increase or decrease in relation to the expression level from the second promoter or signal from the second reporter. In an embodiment of the present invention, the method is carried out along with a negative-control comprising (i) introducing said first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a blank substance which is known to not modulate expression from the promoters or signal from the reporters in the hybrids; and (iii) detecting expression driven by the promoters or signal from the reporters in the hybrids; (iv) comparing the expression level from the first promoter or signal from the first reporter in relation to the expression level from the second promoter or signal from the second reporter in the cell contacted with the blank substance with the expression level from the first promoter or signal from the first reporter in relation to the expression level from the second promoter or signal from the second reporter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth. In an embodiment of the invention, the method is carried out along with a positive-control comprising: (i) introducing said first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a positive-control substance which is known to modulate expression from the promoters or signal from the reporters in the hybrids; (iii) detecting expression driven by the promoters or signal from the reporters in the hybrids; and (iv) comparing the expression level from the first promoter or signal from the first reporter in relation to the expression level from the second promoter or signal from the second reporter in the cell contacted with the positive-control substance with the expression level from the first promoter or signal from the first reporter in relation to the expression level from the second promoter or signal from the second reporter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

[0011] The present invention also provides a method for determining whether a substance inhibits growth of a fungal cell comprising (a) introducing a hybrid comprising a promoter selected from the group consisting of S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter (e.g., SEQ ID NOs: 52-67); operably linked to a reporter (e.g., S. cerevisiae ADE2, S. cerevisiae LYS2, S. cerevisiae TRP1, S. cerevisiae LEU2, S. cerevisiae URA3, S. cerevisiae HIS3, Aequorea victoria GFP mutant 3, Renilla luciferase, Photinus pyralis luciferase, Photinus pyralis luciferase slk mutant, Vibrio fischeri luxA, Vibrio fischeri luxB, Vibrio fischeri luxC, Vibrio fischeri luxD, Vibrio fischeri luxE, Vibrio fischeri luxAB, Vibrio fischeri luxCDABE, Vibrio harveyi luxA, Vibrio harveyi luxB, Vibrio harveyi luxC, Vibrio harveyi luxD, Vibrio harveyi luxE, Vibrio harveyi luxAB, Vibrio harveyi luxCDABE, Photorhabdus luminscens LuxA, Photorhabdus luminscens LuxB, Photorhabdus luminscens LuxC, Photorhabdus luminscens LuxD, Photorhabdus luminscens LuxE, Photorhabdus luminscens LuxCDABE, E. coli lacZ, the Aequorea victoria Aequorin gene, KanMX, pat1, nat1, hph, CAT, Sh Ble, GUS, CYH2 or CAN1 (e.g., SEQ ID NOs: 42-51)) into a suitable fungal cell (e.g., Absidia corymbifera; Absidia spp; Acremonium spp; Ajellomyces capsulatus; Ajellomyces dermatitidis; Alternaria spp; Aphanoascus fulvescens; Apophysomyces spp; Arthroderma benhamiae; Arthroderma falvum; Arthroderma gypseum; Arthroderma incurvatum; Arthroderma otae; Arthroderma vanbreuseghemii; Aspergillus flavus; Aspergillus fumigatus; Aspergillus glaucus; Aspergillus nidulans; Aspergillus niger; Aspergillus oryzae; Aspergillus spp; Aspergillus sydowi; Aspergillus terreus; Aspergillus ustus; Aspergillus versicolor; Aureobasidium pullulans; Basidiomycetes; Beauveria spp; Bipolaris hawaiiensis; Bipolaris spicifera; Bipolaris spp; Bjerkandera adusta; Blastomyces dermatitidis; Blastoschizomyces capitatus; Candida albicans; Candida beigelii; Candida colluculosa; Candida dubliniensis; Candida dubliniensis; Candida famata; Candida famata; Candida glabrata; Candida guilliermondii; Candida haemulonii; Candida holmii; Candida inconspicua; Candida intermedia; Candida keyfyr; Candida krusei; Candida krusei; Candida lambica; Candida lipolytica; Candida lusitaniae; Candida maris; Candida melibiosica; Candida norvegensis; Candida parapsilosis; Candida parapsilosis; Candida pelliculosa; Candida pelliculosa; Candida pseudotropicalis; Candida pulcherrima; Candida rugosa; Candida sake; Candida sphaerica; Candida spp; Candida stellatoidea; Candida tropicalis; Candida tropicalis; Candida viswanathii; Candida zeylanoides; Chrysosporium spp; Cladophialophora bandana; Cladophialophora carrionii; Cladosporium spp; Coccidioides immitis; Cokeromyces recurvatus; Coprinus spp; Cryptococcus albidus; Cryptococcus gattii; Cryptococcus laurentii; Cryptococcus neoformans; Cunninghamella bertholletiae; Cunninghamella spp; Curvularia lunata; Curvularia spp; Dekkera bruxellensis; Epidermophyton floccosum; Epidermophyton floccosum; Exophiala dermatitidis; Exophiala jeanselmei; Exophiala moniliae; Exserohilum rostratum; Filobasidiella neoformans; Fonsecaea pedrosoi; Fusarium dimerum; Fusarium moniliforme; Fusarium oxysporum; Fusarium proliferatum; Fusarium solani; Fusarium spp; Geotrichum candidum; Geotrichum spp; Histoplasma capsulatum; Hortaea werneckii; Issatschenkia orientalis; Kluveromyces lactis; Kluyveromyces marxianus; Madurella grisae; Malassezia furfur; Malassezia globosa; Malassezia obtusa; Malassezia pachydermatis; Malassezia restricta; Malassezia slooffiae; Malassezia sympodialis; Metarrhizium anisopliae; Microsporum audouinii; Microsporum canis; Microsporum fulvum; Microsporum gypseum; Microsporum persicolor; Mucor circinelloides; Mucor hiemalis; Mucor racemosus; Mucor rouxii; Mucor spp; Nattrassia mangiferae; Nectria haematococca; Onychocola canadensis; Paecilomyces lilacinus; Paecilomyces spp; Paecilomyces variotii; Paracoccidioides brasiliensis; Penicillium marneffei; Penicillium spp; Phialophora spp; Phialophora verrucosa; Phoma spp; Pichia anomala; Pichia etchellsii; Pichia guilliermondii; Pichia ohmeri; Pithomyces spp; Pneumocystis carinii; Pseudallescheria boydii; Ramichloridium obovoideum; Rhizomucor miehei; Rhizomucor pusillus; Rhizomucor spp; Rhizopus arrhizus; Rhizopus microsporus; Rhizopus oryzae; Rhizopus schipperae; Rhizopus spp; Rhodotorula mucilaginosa; Rhodotorula rubra; Rhodotorula spp; Saccharomyces cerevisiae; Saccharomyces spp; Sagrahamala spp; Saksenaea vasiformis; Scedosporium apiospermum; Scedosporium prolificans; Schizophyllum commune; Schizosaccharomyces pombe; Scopulariopsis brevicaulis; Scytalidium dimidiatum Ulocladium spp; Sporobolomyces spp; Sporothrix schenckii; Trichoderma spp; Trichophyton krajdenii; Trichophyton mentagrophytes; Trichophyton raubitschekii; Trichophyton rubrum; Trichophyton soudanense; Trichophyton spp; Trichophyton terrestre; Trichophyton tonsurans; Trichophyton verrucosum; Trichophyton violaceum; Trichosporon asahii; Trichosporon beigelii; Trichosporon capitatum; Trichosporon cutaneum; Trichosporon inkin; Trichosporon mucoides; Trichosporon spp; Tritirachium spp; Wangiella dermatitidis or Yarrowia lipolytica); (b) contacting the cell with a substance to be tested for the ability to inhibit growth of the cell; (c) detecting signal from the reporter; and (d) selecting the substance if it causes a reduction in the signal from the reporter and/or calculating the IC of the substance. In an embodiment of the present invention, the method is carried out along with a negative-control comprising: (i) introducing the hybrid into a suitable fungal cell; (ii) contacting the cell with a blank substance which is known to not inhibit fungal cell growth; (iii) detecting signal from the reporter in the hybrid; and (iv) comparing the signal from the reporter in the cell contacted with the blank substance with the signal from the reporter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth. In an embodiment of the invention, the method is carried out along with a positive-control comprising (i) introducing the hybrid into a suitable fungal cell; (ii) contacting the cell with a positive-control substance which is known to inhibit fungal cell growth; (iii) detecting signal from the reporter in the hybrid; and (iv) comparing the signal from the reporter in the cell contacted with the positive-control substance with the signal from the reporter in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

[0012] The present invention further provides a method for determining whether a substance inhibits growth of a fungal cell comprising (a) introducing a first hybrid comprising a first promoter selected from the group consisting of S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter (e.g., SEQ ID NOs: 52-67); operably linked to a first reporter (e.g., S. cerevisiae ADE2, S. cerevisiae LYS2, S. cerevisiae TRP1, S. cerevisiae LEU2, S. cerevisiae URA3, S. cerevisiae HIS3, Aequorea victoria GFP mutant 3, Renilla luciferase, Photinus pyralis luciferase, Photinus pyralis luciferase slk mutant, Vibrio fischeri luxA, Vibrio fischeri luxB, Vibrio fischeri luxC, Vibrio fischeri luxD, Vibrio fischeri luxE, Vibrio fischeri luxAB, Vibrio fischeri luxCDABE, Vibrio harveyi luxA, Vibrio harveyi luxB, Vibrio harveyi luxC, Vibrio harveyi luxD, Vibrio harveyi luxE, Vibrio harveyi luxAB, Vibrio harveyi luxCDABE, Photorhabdus luminscens LuxA, Photorhabdus luminscens LuxB, Photorhabdus luminscens LuxC, Photorhabdus luminscens LuxD, Photorhabdus luminscens LuxE, Photorhabdus luminscens LuxCDABE, E. coli lacZ, the Aequorea victoria Aequorin gene, KanMX, pat1, nat1, hph, CAT, Sh Ble, GUS, CYH2 or CAN1 (e.g., SEQ ID NOs: 42-51)) and a second hybrid comprising a second promoter selected from the group consisting of S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YIL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter (e.g., SEQ ID NOs: 52-67); operably linked to a second reporter (e.g., S. cerevisiae ADE2, S. cerevisiae LYS2, S. cerevisiae TRP1, S. cerevisiae LEU2, S. cerevisiae URA3, S. cerevisiae HIS3, Aequorea victoria GFP mutant 3, Renilla luciferase, Photinus pyralis luciferase, Photinus pyralis luciferase slk mutant, Vibrio fischeri luxA, Vibrio fischeri luxB, Vibrio fischeri luxC, Vibrio fischeri luxD, Vibrio fischeri luxE, Vibrio fischeri luxAB, Vibrio fischeri luxCDABE, Vibrio harveyi luxA, Vibrio harveyi luxB, Vibrio harveyi luxC, Vibrio harveyi luxD, Vibrio harveyi luxE, Vibrio harveyi luxAB, Vibrio harveyi luxCDABE, Photorhabdus luminscens LuxA, Photorhabdus luminscens LuxB, Photorhabdus luminscens LuxC, Photorhabdus luminscens LuxD, Photorhabdus luminscens LuxE, Photorhabdus luminscens LuxCDABE, E. coli lacZ, the Aequorea victoria Aequorin gene, KanMX, pat1, nat1, hph, CAT, Sh Ble, GUS, CYH2 or CAN1 (e.g., SEQ ID NOs: 42-51)) into a suitable fungal cell (e.g., Absidia corymbifera; Absidia spp; Acremonium spp; Ajellomyces capsulatus; Ajellomyces dermatitidis; Alternaria spp; Aphanoascus fulvescens; Apophysomyces spp; Arthroderma benhamiae; Arthroderma fulvum; Arthroderma gypseum; Arthroderma incurvatum; Arthroderma otae; Arthroderma vanbreuseghemii; Aspergillus flavus; Aspergillus fumigatus; Aspergillus glaucus; Aspergillus nidulans; Aspergillus niger; Aspergillus oryzae; Aspergillus spp; Aspergillus sydowi; Aspergillus terreus; Aspergillus ustus; Aspergillus versicolor; Aureobasidium pullulans; Basidiomycetes; Beauveria spp; Bipolaris hawaiiensis; Bipolaris spicifera; Bipolaris spp; Bjerkandera adusta; Blastomyces dermatitidis; Blastoschizomyces capitatus; Candida albicans; Candida beigelii; Candida colluculosa; Candida dubliniensis; Candida dubliniensis; Candida famata; Candida famata; Candida glabrata; Candida guilliermondii; Candida haemulonii; Candida holmii; Candida inconspicua; Candida intermedia; Candida keyfyr; Candida krusei; Candida krusei; Candida lambica; Candida lipolytica; Candida lusitaniae; Candida maris; Candida melibiosica; Candida norvegensis; Candida parapsilosis; Candida parapsilosis; Candida pelliculosa; Candida pelliculosa; Candida pseudotropicalis; Candida pulcherrima; Candida rugosa; Candida sake; Candida sphaerica; Candida spp; Candida stellatoidea; Candida tropicalis; Candida tropicalis; Candida viswanathii; Candida zeylanoides; Chrysosporium spp; Cladophialophora bantiana; Cladophialophora carrionii; Cladosporium spp; Coccidioides immitis; Cokeromyces recurvatus; Coprinus spp; Cryptococcus albidus; Cryptococcus gattii; Cryptococcus laurentii; Cryptococcus neoformans; Cunninghamella bertholletiae; Cunninghamella spp; Curvularia lunata; Curvularia spp; Dekkera bruxellensis; Epidermophyton floccosum; Epidermophyton floccosum; Exophiala dermatitidis; Exophiala jeanselmei; Exophiala moniliae; Exserohilum rostratum; Filobasidiella neoformans; Fonsecaea pedrosoi; Fusarium dimerum; Fusarium moniliforme; Fusarium oxysporum; Fusarium proliferatum; Fusarium solani; Fusarium spp; Geotrichum candidum; Geotrichum spp; Histoplasma capsulatum; Hortaea werneckii; Issatschenkia orientalis; Kluveromyces lactis; Kluyveromyces marxianus; Madurella grisae; Malassezia furfur; Malassezia globosa; Malassezia obtusa; Malassezia pachydermatis; Malassezia restricta; Malassezia slooffiae; Malassezia sympodialis; Metarrhizium anisopliae; Microsporum audouinii; Microsporum canis; Microsporum fulvum; Microsporum gypseum; Microsporum persicolor; Mucor circinelloides; Mucor hiemalis; Mucor racemosus; Mucor rouxii; Mucor spp; Nattrassia mangiferae; Nectria haematococca; Onychocola canadensis; Paecilomyces lilacinus; Paecilomyces spp; Paecilomyces variotii; Paracoccidioides brasiliensis; Penicillium marneffei; Penicillium spp; Phialophora spp; Phialophora verrucosa; Phoma spp; Pichia anomala; Pichia etchellsii; Pichia guilliermondii; Pichia ohmeri; Pithomyces spp; Pneumocystis carinii; Pseudallescheria boydii; Ramichloridium obovoideum; Rhizomucor miehei; Rhizomucor pusillus; Rhizomucor spp; Rhizopus arrhizus; Rhizopus microsporus; Rhizopus oryzae; Rhizopus schipperae; Rhizopus spp; Rhodotorula mucilaginosa; Rhodotorula rubra; Rhodotorula spp; Saccharomyces cerevisiae; Saccharomyces spp; Sagrahamala spp; Saksenaea vasiformis; Scedosporium apiospermum; Scedosporium prolificans; Schizophyllum commune; Schizosaccharomyces pombe; Scopulariopsis brevicaulis; Scytalidium dimidiatum Ulocladium spp; Sporobolomyces spp; Sporothrix schenckii; Trichoderma spp; Trichophyton krajdenii; Trichophyton mentagrophytes; Trichophyton raubitschekii; Trichophyton rubrum; Trichophyton soudanense; Trichophyton spp; Trichophyton terrestre; Trichophyton tonsurans; Trichophyton verrucosum; Trichophyton violaceum; Trichosporon asahii; Trichosporon beigelii; Trichosporon capitatum; Trichosporon cutaneum; Trichosporon inkin; Trichosporon mucoides; Trichosporon spp; Tritirachium spp; Wangiella dermatitidis or Yarrowia lipolytica); wherein said first and second promoter are different and wherein said first and second reporter are different; (b) contacting the cell with a substance to be tested for the ability to inhibit growth of the cell; (c) detecting signal from the reporters; and (d) selecting the substance if it causes a reduction in the signal from both the first and second reporter and/or calculating the IC of the substance. In an embodiment of the present invention, the method is carried out along with a negative-control comprising (i) introducing the first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a blank substance which is known to not inhibit fungal cell growth; (iii) detecting signal from the first and second reporters in the hybrids; and (iv) comparing the signal from the first and second reporters in the cell contacted with the blank substance with the signal from the first and second reporters in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth. In another embodiment of the invention, the method is carried out along with a positive-control comprising (i) introducing the first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a positive control substance which is known to inhibit fungal cell growth; (iii) detecting signal from the first and second promoters in the hybrids; and (iv) comparing the signal from the first and second reporters in the cell contacted with the positive control substance with the signal from the first and second reporters in the cell contacted with the substance to be tested for the ability to inhibit fungal cell growth.

[0013] The present invention also provides a method for determining whether a substance inhibits growth of a malignant cell comprising (a) introducing, into a suitable fungal cell (e.g., Absidia corymbifera; Absidia spp; Acremonium spp; Ajellomyces capsulatus; Ajellomyces dermatitidis; Alternaria spp; Aphanoascus fulvescens; Apophysomyces spp; Arthroderma benhamiae; Arthroderma fulvum; Arthroderma gypseum; Arthroderma incurvatum; Arthroderma otae; Arthroderma vanbreuseghemii; Aspergillus flavus; Aspergillus fumigatus; Aspergillus glaucus; Aspergillus nidulans; Aspergillus niger; Aspergillus oryzae; Aspergillus spp; Aspergillus sydowi; Aspergillus terreus; Aspergillus ustus; Aspergillus versicolor; Aureobasidium pullulans; Basidiomycetes; Beauveria spp; Bipolaris hawaiiensis; Bipolaris spicifera; Bipolaris spp; Bjerkandera adusta; Blastomyces dermatitidis; Blastoschizomyces capitatus; Candida albicans; Candida beigelii; Candida colluculosa; Candida dubliniensis; Candida dubliniensis; Candida famata; Candida famata; Candida glabrata; Candida guilliermondii; Candida haemulonii; Candida holmii; Candida inconspicua; Candida intermedia; Candida keyfyr; Candida krusei; Candida krusei; Candida lambica; Candida lipolytica; Candida lusitaniae; Candida maris; Candida melibiosica; Candida norvegensis; Candida parapsilosis; Candida parapsilosis; Candida pelliculosa; Candida pelliculosa; Candida pseudotropicalis; Candida pulcherrima; Candida rugosa; Candida sake; Candida sphaerica; Candida spp; Candida stellatoidea; Candida tropicalis; Candida tropicalis; Candida viswanathii; Candida zeylanoides; Chrysosporium spp; Cladophialophora bantiana; Cladophialophora carrionii; Cladosporium spp; Coccidioides immitis; Cokeromyces recurvatus; Coprinus spp; Cryptococcus albidus; Cryptococcus gattii; Cryptococcus laurentii; Cryptococcus neoformans; Cunninghamella bertholletiae; Cunninghamella spp; Curvularia lunata; Curvularia spp; Dekkera bruxellensis; Epidermophyton floccosum; Epidermophyton floccosum; Exophiala dermatitidis; Exophiala jeanselmei; Exophiala moniliae; Exserohilum rostratum; Filobasidiella neoformans; Fonsecaea pedrosoi; Fusarium dimerum; Fusarium moniliforme; Fusarium oxysporum; Fusarium proliferatum; Fusarium solani; Fusarium spp; Geotrichum candidum; Geotrichum spp; Histoplasma capsulatum; Hortaea werneckii; Issatschenkia orientalis; Kluveromyces lactis; Kluyveromyces marxianus; Madurella grisae; Malassezia furfur; Malassezia globosa; Malassezia obtusa; Malassezia pachydermatis; Malassezia restricta; Malassezia slooffiae; Malassezia sympodialis; Metarrhizium anisopliae; Microsporum audouinii; Microsporum canis; Microsporum fulvum; Microsporum gypseum; Microsporum persicolor; Mucor circinelloides; Mucor hiemalis; Mucor racemosus; Mucor rouxii; Mucor spp; Nattrassia mangiferae; Nectria haematococca; Onychocola canadensis; Paecilomyces lilacinus; Paecilomyces spp; Paecilomyces variotii; Paracoccidioides brasiliensis; Penicillium marneffei; Penicillium spp; Phialophora spp; Phialophora verrucosa; Phoma spp; Pichia anomala; Pichia etchellsii; Pichia guilliermondii; Pichia ohmeri; Pithomyces spp; Pneumocystis carinii; Pseudallescheria boydii; Ramichloridium obovoideum; Rhizomucor miehei; Rhizomucor pusillus; Rhizomucor spp; Rhizopus arrhizus; Rhizopus microsporus; Rhizopus oryzae; Rhizopus schipperae; Rhizopus spp; Rhodotorula mucilaginosa; Rhodotorula rubra; Rhodotorula spp; Saccharomyces cerevisiae; Saccharomyces spp; Sagrahamala spp; Saksenaea vasiformis; Scedosporium apiospermum; Scedosporium prolificans; Schizophyllum commune; Schizosaccharomyces pombe; Scopulariopsis brevicaulis; Scytalidium dimidiatum Ulocladium spp; Sporobolomyces spp; Sporothrix schenckii; Trichoderma spp; Trichophyton krajdenii; Trichophyton mentagrophytes; Trichophyton raubitschekii; Trichophyton rubrum; Trichophyton soudanense; Trichophyton spp; Trichophyton terrestre; Trichophyton tonsurans; Trichophyton verrucosum; Trichophyton violaceum; Trichosporon asahii; Trichosporon beigelii; Trichosporon capitatum; Trichosporon cutaneum; Trichosporon inkin; Trichosporon mucoides; Trichosporon spp; Tritirachium spp; Wangiella dermatitidis or Yarrowia lipolytica), a first hybrid comprising a first promoter selected from the group consisting of: S. cerevisiae YLR338W, S. cerevisiae YIL066W, S. cerevisiae YNL093W, S. cerevisiae YDR250C, S. cerevisiae YLR381W, S. cerevisiae YBL065W, S. cerevisiae YMR323W and S. cerevisiae YPL171C (e.g., SEQ ID NOs: 8, 22-25, 38, 39 and 68); operably linked to a first reporter (e.g., S. cerevisiae ADE2, S. cerevisiae LYS2, S. cerevisiae TRP1, S. cerevisiae LEU2, S. cerevisiae URA3, S. cerevisiae HIS3, Aequorea victoria GFP mutant 3, Renilla luciferase, Photinus pyralis luciferase, Photinus pyralis luciferase slk mutant, Vibrio fischeri luxA, Vibrio fischeri luxB, Vibrio fischeri luxC, Vibrio fischeri luxD, Vibrio fischeri luxE, Vibrio fischeri luxAB, Vibrio fischeri luxCDABE, Vibrio harveyi luxA, Vibrio harveyi luxB, Vibrio harveyi luxC, Vibrio harveyi luxD, Vibrio harveyi luxE, Vibrio harveyi luxAB, Vibrio harveyi luxCDABE, Photorhabdus luminscens LuxA, Photorhabdus luminscens LuxB, Photorhabdus luminscens LuxC, Photorhabdus luminscens LuxD, Photorhabdus luminscens LuxE, Photorhabdus luminscens LuxCDABE, E. coli lacZ, the Aequorea victoria Aequorin gene, KanMX, pat1, nat1, hph, CAT, Sh Ble, GUS, CYH2 or CAN1 (e.g., SEQ ID NO: 42-51)); and a second hybrid comprising a second promoter selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter (e.g., SEQ ID NOs: 52-67); operably linked to a second reporter (e.g., S. cerevisiae ADE2, S. cerevisiae LYS2, S. cerevisiae TRP1, S. cerevisiae LEU2, S. cerevisiae URA3, S. cerevisiae HIS3, Aequorea victoria GFP mutant 3, Renilla luciferase, Photinus pyralis luciferase, Photinus pyralis luciferase slk mutant, Vibrio fischeri luxA, Vibrio fischeri luxB, Vibrio fischeri luxC, Vibrio fischeri luxD, Vibrio fischeri luxE, Vibrio fischeri luxAB, Vibrio fischeri luxCDABE, Vibrio harveyi luxA, Vibrio harveyi luxB, Vibrio harveyi luxC, Vibrio harveyi luxD, Vibrio harveyi luxE, Vibrio harveyi luxAB, Vibrio harveyi luxCDABE, Photorhabdus luminscens LuxA, Photorhabdus luminscens LuxB, Photorhabdus luminscens LuxC, Photorhabdus luminscens LuxD, Photorhabdus luminscens LuxE, Photorhabdus luminscens LuxCDABE, E. coli lacZ, the Aequorea victoria Aequorin gene, KanMX, pat1, nat1, hph, CAT, Sh Ble, GUS, CYH2 or CAN1 (e.g., SEQ ID NO: 42-51)); (b) contacting the cell with a substance to be tested for the ability to inhibit growth of a malignant cell; (c) detecting expression driven by the first and second promoters; and (d) selecting the substance if it causes the expression level from the first promoter to increase or decrease in relation to the expression level from the second promoter. In an embodiment of the invention, the method is carried out along with a negative-control comprising (i) introducing said first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a blank substance which is known to not modulate expression from the promoters in the hybrids; and (iii) detecting expression driven by the promoters in the hybrids; (iv) comparing the expression level from the first promoter in relation to the expression level from the second promoter in the cell contacted with the blank substance with the expression level from the first promoter in relation to the expression level from the second promoter in the cell contacted with the substance to be tested for the ability to inhibit malignant cell growth. In an embodiment of the invention, the method is carried out along with a positive-control comprising (i) introducing said first and second hybrids into a suitable fungal cell; (ii) contacting the cell with a positive-control substance which is known to modulate expression from the promoters in the hybrids; (iii) detecting expression driven by the promoters in the hybrids; and (iv) comparing the expression level from the first promoter in relation to the expression level from the second promoter in the cell contacted with the positive-control substance with the expression level from the first promoter in relation to the expression level from the second promoter in the cell contacted with the substance to be tested for the ability to inhibit malignant cell growth.

DETAILED DESCRIPTION OF THE INVENTION

[0014] Each of the following isolated polynucleotides (with the exception SEQ ID NOs: 42-51), optionally fused to a reporter, are part of the present invention along with the various methods of use thereof which are described herein.

TABLE-US-00001 TABLE 1 Polynucleic acids of the invention. SEQUENCE SEQUENCE IDENTIFIER S. cerevisiae YOR387C Promoter SEQ ID NO: 1 S. cerevisiae YMR175W Promoter SEQ ID NO: 2 S. cerevisiae YFR026C Promoter SEQ ID NO: 3 S. cerevisiae YJL153C Promoter SEQ ID NO: 4 S. cerevisiae YPL033C Promoter SEQ ID NO: 5 S. cerevisiae YOL058W Promoter SEQ ID NO: 6 S. cerevisiae YOR255W Promoter SEQ ID NO: 7 S. cerevisiae YDR250C Promoter SEQ ID NO: 8 S. cerevisiae YDR446W Promoter SEQ ID NO: 9 S. cerevisiae YDR536W Promoter SEQ ID NO: 10 S. cerevisiae YOR255W Promoter SEQ ID NO: 11 S. cerevisiae YDL243C Promoter SEQ ID NO: 12 S. cerevisiae YDR256C Promoter SEQ ID NO: 13 S. cerevisiae YFL020C Promoter SEQ ID NO: 14 S. cerevisiae YPL205C Promoter SEQ ID NO: 15 S. cerevisiae YGL205W Promoter SEQ ID NO: 16 S. cerevisiae YGL117W Promoter SEQ ID NO: 17 S. cerevisiae YHR029C Promoter SEQ ID NO: 18 S. cerevisiae YML116W Promoter SEQ ID NO: 19 S. cerevisiae YJR109C Promoter SEQ ID NO: 20 S. cerevisiae YCL030C Promoter SEQ ID NO: 21 S. cerevisiae YLR338W Promoter SEQ ID NO: 22 S. cerevisiae YIL066W-A Promoter SEQ ID NO: 23 S. cerevisiae YNL093W Promoter SEQ ID NO: 24 S. cerevisiae YLR381W Promoter SEQ ID NO: 25 S. cerevisiae YKL159C Promoter SEQ ID NO: 26 S. cerevisiae YIL058W Promoter SEQ ID NO: 27 S. cerevisiae YKR037C Promoter SEQ ID NO: 28 S. cerevisiae YNL279W Promoter SEQ ID NO: 29 S. cerevisiae YOR032C Promoter SEQ ID NO: 30 S. cerevisiae YML058W Promoter SEQ ID NO: 31 S. cerevisiae YMR303C Promoter SEQ ID NO: 32 S. cerevisiae YJL153C Promoter SEQ ID NO: 33 S. cerevisiae YLR092W Promoter SEQ ID NO: 34 S. cerevisiae YFL052W Promoter SEQ ID NO: 35 S. cerevisiae YIR017C Promoter SEQ ID NO: 36 S. cerevisiae YLL062C Promoter SEQ ID NO: 37 S. cerevisiae YMR323W Promoter SEQ ID NO: 38 S. cerevisiae YPL171C Promoter SEQ ID NO: 39 S. cerevisiae YER065C Promoter SEQ ID NO: 40 S. cerevisiae YDR114C Promoter SEQ ID NO: 41 S. cerevisiae ADE2 SEQ ID NO: 42 S. cerevisiae LYS2 SEQ ID NO: 43 S. cerevisiae TRP1 SEQ ID NO: 44 S. cerevisiae LEU2 SEQ ID NO: 45 S. cerevisiae URA3 SEQ ID NO: 46 S. cerevisiae HIS3 SEQ ID NO: 47 Aequorea victoria GFP mutant 3 SEQ ID NO: 48 Renilla luciferase SEQ ID NO: 49 Photinus pyralis luciferase SEQ ID NO: 50 E. coli lacZ SEQ ID NO: 51 S. cerevisiae YHR082C Promoter SEQ ID NO: 52 S. cerevisiae YDL126C Promoter SEQ ID NO: 53 S. cerevisiae YBR106W Promoter SEQ ID NO: 54 S. cerevisiae YLL043W Promoter SEQ ID NO: 55 S. cerevisiae YPR108W Promoter SEQ ID NO: 56 S. cerevisiae YIL041W Promoter SEQ ID NO: 57 S. cerevisiae YJL166W Promoter SEQ ID NO: 58 S. cerevisiae YDR165W Promoter SEQ ID NO: 59 S. cerevisiae YLR330W Promoter SEQ ID NO: 60 S. cerevisiae YDL058W Promoter SEQ ID NO: 61 S. cerevisiae YHR012W Promoter SEQ ID NO: 62 S. cerevisiae YKL053W Promoter SEQ ID NO: 63 S. cerevisiae YKL196C Promoter SEQ ID NO: 64 S. cerevisiae YDL103C Promoter SEQ ID NO: 65 S. cerevisiae YLR427W Promoter SEQ ID NO: 66 S. cerevisiae YLL020C Promoter SEQ ID NO: 67 S. cerevisiae YBL065W Promoter SEQ ID NO: 68 PR131 Primer SEQ ID NO: 69 PR132 Primer SEQ ID NO: 70 PR161 Primer SEQ ID NO: 71 PR 162Primer SEQ ID NO: 72 PHO 5 signal sequence SEQ ID NO: 73 PR172 Primer SEQ ID NO: 74 PR173B Primer SEQ ID NO: 75 PR207 Primer SEQ ID NO: 76 PR208 Primer SEQ ID NO: 77 PR213 Primer SEQ ID NO: 78 PR214Primer SEQ ID NO: 79 PR167 Primer SEQ ID NO: 80 PR168SLK Primer SEQ ID NO: 81 PHO5 signal sequence SEQ ID NO: 82 PR174 Primer SEQ ID NO: 83 PR175B Primer SEQ ID NO: 84 pSPRT47 plasmid sequence SEQ ID NO: 85 pSPRT50 plasmid sequence SEQ ID NO: 86 pSPRT190 plasmid sequence SEQ ID NO: 87 pSPRT192 plasmid sequence SEQ ID NO: 88

[0015] Since the Saccharmomyces cerevisiae genome has been sequenced, the promoter sequences identified in Table 1 can also be found in publicly available databases including the Saccharomyces Genome Database; Stanford University, Calif.

[0016] The term "fungal cell" or "fungi" or "fungus" includes, but is not limited to, any of the following organisms: Absidia corymbifera; Absidia spp; Acremonium spp; Ajellomyces capsulatus; Ajellomyces dermatitidis; Alternaria spp; Aphanoascus fulvescens; Apophysomyces spp; Arthroderma benhamiae; Arthroderma fulvum; Arthroderma gypseum; Arthroderma incurvatum; Arthroderma otae; Arthroderma vanbreuseghemii; Aspergillus flavus; Aspergillus fumigatus; Aspergillus glaucus; Aspergillus nidulans; Aspergillus niger; Aspergillus oryzae; Aspergillus spp; Aspergillus sydowi; Aspergillus terreus; Aspergillus ustus; Aspergillus versicolor; Aureobasidium pullulans; Basidiomycetes; Beauveria spp; Bipolaris hawaiiensis; Bipolaris spicifera; Bipolaris spp; Bjerkandera adusta; Blastomyces dermatitidis; Blastoschizomyces capitatus; Candida albicans; Candida beigelii; Candida colluculosa; Candida dubliniensis; Candida dubliniensis; Candida famata; Candida famata; Candida glabrata; Candida guilliermondii; Candida haemulonii; Candida holmii; Candida inconspicua; Candida intermedia; Candida keyfyr; Candida krusei; Candida krusei; Candida lambica; Candida lipolytica; Candida lusitaniae; Candida maris; Candida melibiosica; Candida norvegensis; Candida parapsilosis; Candida parapsilosis; Candida pelliculosa; Candida pelliculosa; Candida pseudotropicalis; Candida pulcherrima; Candida rugosa; Candida sake; Candida sphaerica; Candida spp; Candida stellatoidea; Candida tropicalis; Candida tropicalis; Candida viswanathii; Candida zeylanoides; Chrysosporium spp; Cladophialophora bantiana; Cladophialophora carrionii; Cladosporium spp; Coccidioides immitis; Cokeromyces recurvatus; Coprinus spp; Cryptococcus albidus; Cryptococcus gattii; Cryptococcus laurentii; Cryptococcus neoformans; Cunninghamella bertholletiae; Cunninghamella spp; Curvularia lunata; Curvularia spp; Dekkera bruxellensis; Epidermophyton floccosum; Epidermophyton floccosum; Exophiala dermatitidis; Exophiala jeanselmei; Exophiala moniliae; Exserohilum rostratum; Filobasidiella neoformans; Fonsecaea pedrosoi; Fusarium dimerum; Fusarium moniliforme; Fusarium oxysporum; Fusarium prolaferatum; Fusarium solani; Fusarium spp; Geotrichum candidum; Geotrichum spp; Histoplasma capsulatum; Hortaea werneckii; Issatschenkia orientalis; Kluveromyces lactis; Kluyveromyces marxianus; Madurella grisae; Malassezia furfur; Malassezia globosa; Malassezia obtusa; Malassezia pachydermatis; Malassezia restricta; Malassezia slooffiae; Malassezia sympodialis; Metarrhizium anisopliae; Microsporum audouinii; Microsporum canis; Microsporum fulvum; Microsporum gypseum; Microsporum persicolor; Mucor circinelloides; Mucor hiemalis; Mucor racemosus; Mucor rouxii; Mucor spp; Nattrassia mangiferae; Nectria haematococca; Onychocola canadensis; Paecilomyces lilacinus; Paecilomyces spp; Paecilomyces variotii; Paracoccidioides brasiliensis; Penicillium marneffei; Penicillium spp; Phialophora spp; Phialophora verrucosa; Phoma spp; Pichia anomala; Pichia etchellsii; Pichia guilliermondii; Pichia ohmeri; Pithomyces spp; Pneumocystis carinii; Pseudallescheria boydii; Ramichloridium obovoideum; Rhizomucor miehei; Rhizomucor pusillus; Rhizomucor spp; Rhizopus arrhizus; Rhizopus microsporus; Rhizopus oryzae; Rhizopus schipperae; Rhizopus spp; Rhodotorula mucilaginosa; Rhodotorula rubra; Rhodotorula spp; Saccharomyces cerevisiae; Saccharomyces spp; Sagrahamala spp; Saksenaea vasiformis; Scedosporium apiospermum; Scedosporium prolificans; Schizophyllum commune; Schizosaccharomyces pombe; Scopulariopsis brevicaulis; Scytalidium dimidiatum Ulocladium spp; Sporobolomyces spp; Sporothrix schenckii; Trichoderma spp; Trichophyton krajdenii; Trichophyton mentagrophytes; Trichophyton raubitschekii; Trichophyton rubrum; Trichophyton soudanense; Trichophyton spp; Trichophyton terrestre; Trichophyton tonsurans; Trichophyton verrucosum; Trichophyton violaceum; Trichosporon asahii; Trichosporon beigelii; Trichosporon capitatum; Trichosporon cutaneum; Trichosporon inkin; Trichosporon mucoides; Trichosporon spp; Tritirachium spp; Wangiella dermatitidis or Yarrowia lipolytica.

[0017] A substance "inhibits" growth of a cell (e.g., a fungal cell) if it reduces the ability of the cell to grow, to any degree (e.g., 10%, 25%, 50%, 75%, 90%, 99%, 100%), as compared to a similar cell's growth in the absence of the substance.

[0018] A promoter's expression level is "modulated" if it is increased or decreased to any degree.

Molecular Biology

[0019] In accordance with the present invention there may be employed conventional molecular biology, microbiology, and recombinant DNA techniques within the skill of the art. Such techniques are explained in the literature. See, e.g., Sambrook, Fritsch & Maniatis, Molecular Cloning: A Laboratory Manual, Second Edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (herein "Sambrook, et al., 1989"); DNA Cloning: A Practical Approach, Volumes I and II (D. N. Glover ed. 1985); Oligonucleotide Synthesis (M. J. Gait ed. 1984); Nucleic Acid Hybridization (B. D. Hames & S. J. Higgins eds. (1985)); Transcription And Translation (B. D. Hames & S. J. Higgins, eds. (1984)); Animal Cell Culture (R. I. Freshney, ed. (1986)); Immobilized Cells And Enzymes (IRL Press, (1986)); B. Perbal, A Practical Guide To Molecular Cloning (1984); F. M. Ausubel, et al. (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, Inc. (1994).

[0020] A "polynucleotide", "nucleic acid" or "nucleic acid molecule" includes the polymeric form of ribonucleosides (adenosine, guanosine, uridine or cytidine; "RNA molecules") or deoxyribonucleosides (deoxyadenosine, deoxyguanosine, deoxythymidine, or deoxycytidine; "DNA molecules"), or any phosphoester analogs thereof, such as phosphorothioates and thioesters, in single stranded form, double-stranded form or otherwise.

[0021] A "polynucleotide sequence", "nucleic acid sequence" or "nucleotide sequence" is a series of nucleotide bases (also called "nucleotides") in a nucleic acid, such as DNA or RNA, and means any chain of two or more nucleotides.

[0022] A "coding sequence" or a sequence "encoding" an expression product, such as a RNA, polypeptide, protein, or enzyme, is a nucleotide sequence that, when expressed, results in production of the product.

[0023] The term "gene" means a DNA sequence that codes for or corresponds to a particular sequence of ribonucleotides or amino acids which comprise all or part of one or more RNA molecules, proteins or enzymes, and may or may not include regulatory DNA sequences, such as promoter sequences, which determine, for example, the conditions under which the gene is expressed. Genes may be transcribed from DNA to RNA which may or may not be translated into an amino acid sequence.

[0024] As used herein, the term "oligonucleotide" refers to a nucleic acid, generally of no more than about 100 nucleotides (e.g., 30, 40, 50, 60, 70, 80, or 90), that may be hybridizable to a genomic DNA molecule, a cDNA molecule, or an mRNA molecule encoding a gene, mRNA, cDNA, or other nucleic acid of interest. Oligonucleotides can be labeled, e.g., by incorporation of .sup.32P-nucleotides, .sup.3H-nucleotides, .sup.14C-nucleotides, .sup.35S-nucleotides or nucleotides to which a label, such as biotin, has been covalently conjugated. In one embodiment, a labeled oligonucleotide can be used as a probe to detect the presence of a nucleic acid. In another embodiment, oligonucleotides (one or both of which may be labeled) can be used as PCR primers, either for cloning full length or a fragment of the gene, or to detect the presence of nucleic acids. Generally, oligonucleotides are prepared synthetically, preferably on a nucleic acid synthesizer.

[0025] A "protein sequence", "peptide sequence" or "polypeptide sequence" or "amino acid sequence" refers to a series of two or more amino acids in a protein, peptide or polypeptide.

[0026] "Protein", "peptide" or "polypeptide" includes a contiguous string of two or more amino acids.

[0027] The term "isolated polynucleotide" or "isolated polypeptide" includes a polynucleotide (e.g., RNA or DNA molecule, or a mixed polymer) or a polypeptide, respectively, which is partially or fully separated from other components that are normally found in cells or in recombinant DNA expression systems or any other contaminant. These components include, but are not limited to, cell membranes, cell walls, ribosomes, polymerases, serum components and extraneous genomic sequences.

[0028] An isolated polynucleotide or polypeptide will, preferably, be an essentially homogeneous composition of molecules but may contain some heterogeneity.

[0029] "Amplification" of DNA as used includes the use of polymerase chain reaction (PCR) to increase the concentration of a particular DNA sequence within a mixture of DNA sequences. For a description of PCR see Saiki, et al., Science (1988) 239:487.

[0030] The term "host cell" includes any cell of any organism that is selected, modified, transfected, transformed, grown, or used or manipulated in any way, for the production of a substance by the cell, for example the expression or replication, by the cell, of a gene, a DNA or RNA sequence or a protein. For example, a host cell may be a bacteria such as E. coli. The scope of the present invention includes a host cell comprising any of the responsive promoters or baseline promoters described herein along with fusions comprising a responsive promoter or baseline promoter fused to a reporter (e.g., a reporter gene). Preferably, the promoter or the fusion is in a vector or is genetically integrated into a chromosome of the host cell. A host cell can be, for example, a Saccharomyces cerevisiae cell (e.g., strain MS1554 or strain WT1554).

[0031] The sequence of a nucleic acid may be sequenced by any method known in the art (e.g., chemical sequencing or enzymatic sequencing). "Chemical sequencing" of DNA may denote methods such as that of Maxam and Gilbert (Proc. Natl. Acad. Sci. USA (1977) 74:560), in which DNA is randomly cleaved using individual base-specific reactions. "Enzymatic sequencing" of DNA may denote methods such as that of Sanger (Sanger, et al., Proc. Natl. Acad. Sci. USA (1977) 74:5463).

[0032] Aside from the responsive promoters of the invention, nucleic acids of the invention can be flanked by other natural regulatory (expression control) sequences, which may be associated with heterologous sequences, including internal ribosome entry sites (IRES) and other ribosome binding site sequences, enhancers, response elements, suppressors, signal sequences, polyadenylation sequences, introns, 5'- and 3'-non-coding regions, and the like.

[0033] In general, a "promoter" or "promoter sequence" is a DNA regulatory region capable of binding an RNA polymerase in a cell (e.g., directly or through other promoter-bound proteins or substances) and initiating transcription of a coding sequence. A promoter sequence is, in general, bounded at its 3' terminus by the transcription initiation site and extends upstream (5' direction) to include the minimum number of bases or elements necessary to initiate transcription at any level. Within the promoter sequence may be found a transcription initiation site (conveniently defined, for example, by mapping with nuclease S1), as well as protein binding domains (consensus sequences) responsible for the binding of RNA polymerase. The promoter may be operably associated with other expression control sequences, including enhancer and repressor sequences or with a nucleic acid of the invention.

[0034] A coding sequence (e.g., of a reporter) is "operably linked to", "under the control of", "functionally associated with" or "operably associated with" a transcriptional and translational control sequence (e.g., a responsive promoter) in a cell when the sequence directs RNA polymerase mediated transcription of the coding sequence into RNA, preferably mRNA, which then may be RNA spliced (if it contains introns) and, optionally, translated into a protein encoded by the coding sequence.

[0035] The terms "express" and "expression" mean allowing or causing the information in a gene, RNA or DNA sequence to become manifest; for example, producing a protein by activating the cellular functions involved in transcription and translation of a corresponding gene. A DNA sequence is expressed in or by a cell to form an "expression product" such as an RNA (e.g., mRNA) or a protein. The expression product itself may also be said to be "expressed" by the cell.

[0036] The term "transformation" means the introduction of a nucleic acid into a cell. The introduced gene or sequence may be called a "clone". A host cell that receives the introduced DNA or RNA has been "transformed" and is a "transformant" or a "clone." The DNA or RNA introduced to a host cell can come from any source, including cells of the same genus or species as the host cell, or from cells of a different genus or species.

[0037] The present invention includes vectors which comprise polynucleotides of the invention (e.g., SEQ ID NOs: 1-41 or 52-68 or a functional variant thereof). The term "vector" includes a vehicle (e.g., a plasmid) by which a DNA or RNA sequence can be introduced into a host cell, so as to transform the host and, optionally, promote expression and/or replication of the introduced sequence. In general, a plasmid is circular, includes an origin (e.g., 2 .mu.m origin) and, preferably includes a selectable marker. In plasmids which can be maintained in yeast, the most commonly used yeast markers include URA3, HIS3, LEU2, TRP1 and LYS2, which complement specific auxotrophic mutations in a yeast host cell, such as ura3-52, his3-D1, leu2-D1, trp1-D1 and lys2-201, respectively. If the plasmid can be maintained in E. coli, it will include a bacterial origin (ori) and a selectable market such as the .beta.-lactamase gene (bla or AMP.sup.r). Commonly used yeast/E. coli shuttle vectors are the Yip (see Myers et al., Gene 45: 299-310, (1986)), Yep (see Myers et al., Gene 45: 299-310, (1986)), YCp and YRp plasmids. The YIp integrative vectors do not replicate autonomously, but integrate into the genome at low frequencies by homologous recombination. The YEp yeast episomal plasmid vectors replicate autonomously because of the presence of a segment of the yeast 2 .mu.m plasmid that serves as an origin of replication (2 .mu.m ori). The 2 .mu.m ori is responsible for the high copy-number and high frequency of transformation of YEp vectors. The YCp yeast centromere plasmid vectors are autonomously replicating vectors containing centromere sequences, CEN, and autonomously replicating sequences, ARS. The YCp vectors are typically present at very low copy numbers, from 1 to 3 per cell. Autonomously replicating plasmids (YRp) which carry a yeast origin of replication (ARS sequence; but not centromere) that allows the transformed plasmids to be propagated several hundred-fold. YIp, YEp, YCp and YRp are commonly known in the art and widely available. Another acceptable yeast vector is a yeast artificial chromosome (YAC). A yeast artificial chromosome is a biological vector. It is an artificially constructed chromosome and contains the telomeric, centromeric, and replication origin sequences needed for replication in yeast cells (see Marchuk et al., Nucleic Acids Res. 16(15):7743 (1988); Rech et al., Nucleic Acids Res. 18(5):1313 (1990)).

[0038] Vectors that could be used in this invention include plasmids, viruses, bacteriophage, integratable DNA fragments, and other vehicles that may facilitate introduction of the nucleic acids into the genome of the host. Plasmids are the most commonly used form of vector but all other forms of vectors which serve a similar function and which are, or become, known in the art are suitable for use herein. See, e.g., Pouwels, et al., Cloning Vectors: A Laboratory Manual, 1985 and Supplements, Elsevier, N.Y., and Rodriguez et al. (eds.), Vectors: A Survey of Molecular Cloning Vectors and Their Uses, 1988, Buttersworth, Boston, Mass.

[0039] A polynucleotides may be expressed in an expression system. The term "expression system" means a host cell and compatible vector which, under suitable conditions, can express a protein or nucleic acid which is carried by the vector and introduced to the host cell. Common expression systems include E. coli host cells and plasmid vectors, insect host cells and Baculovirus vectors, and mammalian host cells and vectors.

[0040] The present invention also contemplates any superficial or slight modification to the responsive promoter and baseline promoter nucleotide sequences of the invention. For example, the present invention includes any "functional variant" of any responsive promoter of the present invention (e.g., SEQ ID NOs: 1-41 or 68) or of any baseline promoter of the present invention (e.g., SEQ ID NOs: 52-67). A functional variant of a promoter of the present invention includes any sequence variant that retains the ability to cause the expression of a downstream sequence (e.g., reporter such as SEQ ID NOs: 42-51) at any detectable level. Methods for determining whether a particular promoter sequence variant retains the ability to promoter expression of a down-stream sequence are conventional and well known in the art.

[0041] The present invention contemplates sequence conservative variants of the nucleic acids (e.g., SEQ ID NOs: 1-41 or 52-68). "Sequence-conservative variants" of a polynucleotide sequence (e.g., SEQ ID NOs: 1-41 or 52-68) are those in which a change of one or more nucleotides results in no significant alteration in the function of the promoter.

[0042] The present invention includes nucleic acids which hybridize to the responsive promoter and baseline promoter polynucleotides of the invention (e.g., SEQ ID NOs: 1-41 or 52-68). Preferably, the nucleic acids hybridize under low stringency conditions, more preferably under moderate stringency conditions and most preferably under high stringency conditions. A nucleic acid molecule is "hybridizable" to another nucleic acid molecule when a single stranded form of the nucleic acid molecule can anneal to the other nucleic acid molecule under the appropriate conditions of temperature and solution ionic strength (see Sambrook, et al., supra). The conditions of temperature and ionic strength determine the "stringency" of the hybridization. Typical low stringency hybridization conditions may be 55.degree. C., 5.times.SSC, 0.1% SDS, 0.25% milk, and no formamide; or 30% formamide, 5.times.SSC, 0.5% SDS. Typical, moderate stringency hybridization conditions are similar to the low stringency conditions except the hybridization is carried out in 40% formamide, with 5.times. or 6.times.SSC. High stringency hybridization conditions are similar to low stringency conditions except the hybridization conditions are carried out in 50% formamide, 5.times. or 6.times.SSC and, optionally, at a higher temperature (e.g., 57.degree. C., 59.degree. C., 60.degree. C., 62.degree. C., 63.degree. C., 65.degree. C. or 68.degree. C.). In general, SSC is 0.15M NaCl and 0.015M Na-citrate. Hybridization requires that the two nucleic acids contain complementary sequences, although, depending on the stringency of the hybridization, mismatches between bases are possible. The appropriate stringency for hybridizing nucleic acids depends on the length of the nucleic acids and the degree of complementation, variables well known in the art. The greater the degree of similarity or homology between two nucleotide sequences, the higher the stringency under which the nucleic acids may hybridize. For hybrids of greater than 100 nucleotides in length, equations for calculating the melting temperature have been derived (see Sambrook, et al., supra, 9.50-9.51). For hybridization with shorter nucleic acids, i.e., oligonucleotides, the position of mismatches becomes more important, and the length of the oligonucleotide determines its specificity (see Sambrook, et al., supra, 11.7-11.8).

[0043] Also included in the present invention are polynucleotides comprising nucleotide sequences which are at least about 70% identical, preferably at least about 80% identical, more preferably at least about 90% identical and most preferably at least about 95% identical (e.g., 95%, 96%, 97%, 98%, 99%, 100%) to the reference responsive promoter and baseline promoter polynucleotides (e.g., SEQ ID NO: 1-41 and 52-68) when the comparison is performed by a BLAST algorithm wherein the parameters of the algorithm are selected to give the largest match between the respective sequences over the entire length of the respective reference sequences.

[0044] The following references regarding the BLAST algorithm are herein incorporated by reference: BLAST ALGORITHMS: Altschul, S. F., et al., J. Mol. Biol. (1990) 215:403-410; Gish, W., et al., Nature Genet. (1993) 3:266-272; Madden, T. L., et al., Meth. Enzymol. (1996) 266:131-141; Altschul, S. F., et al., Nucleic Acids Res. (1997) 25:3389-3402; Zhang, J., et al., Genome Res. (1997) 7:649-656; Wootton, J. C., et al., Comput. Chem. (1993) 17:149-163; Hancock, J. M., et al., Comput. Appl. Biosci. (1994) 10:67-70; ALIGNMENT SCORING SYSTEMS: Dayhoff, M. O., et al., "A model of evolutionary change in proteins." in Atlas of Protein Sequence and Structure, (1978) vol. 5, suppl. 3. M. O. Dayhoff (ed.), pp. 345-352, Natl. Biomed. Res. Found., Washington, D.C.; Schwartz, R. M., et al., "Matrices for detecting distant relationships." in Atlas of Protein Sequence and Structure, (1978) vol. 5, suppl. 3." M. O. Dayhoff (ed.), pp. 353-358, Natl. Biomed. Res. Found., Washington, D.C.; Altschul, S.F., J. Mol. Biol. (1991) 219:555-565; States, D. J., et al., Methods (1991) 3:66-70; Henikoff, S., et al., Proc. Natl. Acad. Sci. USA (1992)89:10915-10919; Altschul, S. F., et al., J. Mol. Evol. (1993) 36:290-300; ALIGNMENT STATISTICS: Karlin, S., et al., Proc. Natl. Acad. Sci. USA (1990) 87:2264-2268; Karlin, S., et al., Proc. Natl. Acad. Sci. USA (1993) 90:5873-5877; Dembo, A., et al., Ann. Prob. (1994) 22:2022-2039; and Altschul, S. F. "Evaluating the statistical significance of multiple distinct local alignments." in Theoretical and Computational Methods in Genome Research (S. Suhai, ed.), (1997) pp. 1-14, Plenum, N.Y.

Promoters and Screening Assays

[0045] The present invention provides several "gene responsive promoters", "responsive promoters" or "biomarkers" which have been identified in S. cerevisiae (e.g., SEQ ID NOs: 1-41 or 68). The expression from each responsive promoter has been correlated with the function of a particular gene which is essential in S. cerevisiae. Below, in table 2, each gene ("gene" column) whose temperature-sensitive allele was inactivated by shift to the restrictive temperature is correlated with a promoter ("RP" column) which was up-regulated in response to the shift along with the function of the gene. The responsive promoters of the present invention can be used to identify substances that modulate (increase or decrease) the function of an essential fungal gene, for example, in the assays described below. A substance which modulates (increases or decreases) the function of any of the essential genes mentioned herein is useful as an anti-fungal compound which can be used, inter alia, to treat or prevent fungal infections. For example, if the substance inhibits the activity of the essential gene's translated product, it will lead to the death, or decreased growth, of the host cell carrying the gene. Since fungi, such as Saccharomyces cerevisiae, Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus and Candida albicans, are genetically related, a substance which modulates an essential gene in S. cerevisiae and kills the cell or inhibits its growth will be lethal to or inhibit the growth of all of the cell types. A substance which modulates the function of any of the essential genes mentioned herein is also useful to the treatment or prevention of cancer (e.g., by inhibition of the growth of a malignant cell).

[0046] Substances which inhibit fungal cell growth or malignant cell growth reduce it by any measurable degree. For example, a substance which inhibits fungal cell or malignant cell growth can kill the cell completely or reduce its level of growth by 10%. A substance which inhibits fungal cell growth can be "fungistatic" in that it inhibits growth of the cell to any measurable degree without killing the cell.

[0047] One embodiment of the present invention includes a screening assay wherein a biomarker of the present invention (e.g., SEQ ID NO:1-41 or 68 or a functional variant thereof) is used to identify a substance which inhibits fungal cell growth (a modulator of an essential fungal gene) comprising the following steps: (a) introducing a hybrid comprising a responsive promoter (e.g., SEQ ID NO:1-41 or 68 or a functional variant thereof) operably linked to a reporter (e.g., reporter gene such as SEQ ID NO: 42-51 or a functional variant thereof) into a suitable cell (e.g., a fugal cell); (b) contacting the cell with a substance to be tested for the ability to inhibit fungal cell growth; (c) detecting expression driven by the promoter in the hybrid; (d) selecting the substance if it modulates expression from the responsive promoter.

[0048] If the level of expression driven by the promoter is modulated (increased or decreased) in response to the substance, this indicates that the substance does modulate the activity of the essential gene and inhibits fungal cell growth.

[0049] In an embodiment of the invention, a negative-control screening assay is also carried out. In this embodiment, a fungal cell comprising the hybrid is contacted with the substance being tested and another, separate cell comprising the same hybrid is contacted with a blank (i.e., a substance known not to modulate the expression level from the promoter) such as DMSO, water or buffer. If the substance being tested increases or decreases the expression level from the promoter in relation to the expression level from the promoter/reporter in the cell contacted with the blank, this indicates that the substance does modulate the expression level from the responsive promoter, and, that it does modulate the activity of the essential fungal gene (i.e., the substance is an anti-fungal substance). A positive-control screening assay can also be performed. In the positive-control assay, a fungal cell comprising the hybrid is contacted with the substance being tested and another, separate cell comprising the same hybrid is contacted with a positive-control substance known to modulate the expression level from the promoter. If the substance being tested and the positive-control substance both increase or decrease the expression level from the promoter, this indicates that the substance being tested does modulate the expression level from the responsive promoter, and, that it does modulate the activity of the essential fungal gene (i.e., the substance inhibits fungal cell growth).

[0050] Another embodiment of the present invention includes a ratiometric screening assay wherein a responsive promoter of the present invention is used to identify a substance which inhibits fungal cell growth (a modulator of an essential fungal gene) comprising the following steps: (a) introducing, into a suitable cell, a first hybrid comprising a first (responsive) promoter selected from the group consisting of: S. cerevisiae YOR387C Promoter, S. cerevisiae YMR175W Promoter, S. cerevisiae YFR026C Promoter, S. cerevisiae YJL153C Promoter, S. cerevisiae YPL033C Promoter, S. cerevisiae YOL058W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDR250C Promoter, S. cerevisiae YDR446W Promoter, S. cerevisiae YDR536W Promoter, S. cerevisiae YOR255W Promoter, S. cerevisiae YDL243C Promoter S. cerevisiae YDR256C Promoter, S. cerevisiae YFL020C Promoter, S. cerevisiae YPL205C Promoter, S. cerevisiae YGL205W Promoter, S. cerevisiae YGL117W Promoter, S. cerevisiae YHR029C Promoter, S. cerevisiae YML116W Promoter S. cerevisiae YJR109C Promoter, S. cerevisiae YCL030C Promoter, S. cerevisiae YLR338W Promoter, S. cerevisiae YIL066W-A Promoter, S. cerevisiae YNL093W Promoter, S. cerevisiae YLR381W Promoter, S. cerevisiae YKL159C Promoter, S. cerevisiae YIL058W Promoter, S. cerevisiae YKR037C Promoter, S. cerevisiae YNL279W Promoter, S. cerevisiae YOR032C Promoter, S. cerevisiae YML058W Promoter, S. cerevisiae YMR303C Promoter, S. cerevisiae YJL153C Promoter S. cerevisiae YLR092W Promoter, S. cerevisiae YFL052W Promoter, S. cerevisiae YIR017C Promoter, S. cerevisiae YLL062C Promoter, S. cerevisiae YMR323W Promoter S. cerevisiae YPL171C Promoter, S. cerevisiae YER065C Promoter and S. cerevisiae YDR114C Promoter (e.g., SEQ ID NO: 1-41 or 68 or a functional variant thereof); operably linked to a first reporter (e.g., SEQ ID NO: 42-51 or a functional variant thereof); and a second hybrid comprising a second (baseline) promoter selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter (e.g., SEQ ID NO: 52-67 or a functional variant thereof); operably linked to a second reporter (e.g., SEQ ID NO: 42-51 or a functional variant thereof); (b) contacting the cell with a substance to be tested for the ability to inhibit fungal cell growth; (c) detecting expression driven by the first and second promoters; and (d) selecting the substance if it causes the first (gene responsive) promoter expression level to increase or decrease in relation to the expression level from the second (baseline) promoter.

[0051] In the ratiometric assay, a responsive promoter expression level that does not increase or decrease in relation to the expression level from the baseline promoter, in response to contacting the cell with the substance being tested for anti-fungal activity, indicates that the substance does not modulate the expression level from the responsive promoter, and, that it does not modulate the activity of the essential fungal gene. A responsive promoter expression level that increases or decreases in relation to the expression level from the baseline promoter, in response to contacting the cell with the substance being tested for anti-fungal activity, indicates that the substance does modulate the expression level from the responsive promoter, and, that it does modulate the activity of the essential fungal gene (i.e., it inhibits fungal growth).

[0052] In an embodiment of the invention, a negative-control ratiometric screening assay is also carried out. In this embodiment, a cell comprising the first and second hybrid is contacted with the substance being tested and another, separate cell comprising the first and second hybrid is contacted with a blank (i.e., a substance known not to modulate the expression level from the first or second promoters) such as DMSO, water or buffer. If the substance being tested increases or decreases the expression level from the first promoter in relation to the expression level from the second promoter and if the blank fails to increase or decrease the expression level from the first promoter in relation to the second promoter expression level, this indicates that the substance does modulate the expression level from the responsive promoter, and, that it does modulate the activity of the essential fungal gene (i.e., the substance is an anti-fungal substance). A positive-control ratiometic screening assay may also be performed. In the positive-control assay, a cell comprising the first and second hybrid is contacted with the substance being tested and another, separate cell comprising the first and second hybrid is contacted with a positive-control substance known to modulate the expression level from the first promoter in relation to the expression level from the second promoter. If the substance being tested and the positive-control substance both modulate the expression level from the first promoter in relation to the expression level from the second promoter, this indicates that the substance being tested does modulate the expression level from the responsive promoter/reporter, and, that it does modulate the activity of the essential fungal gene (i.e., the substance inhibits fungal cell growth).

[0053] Up-regulation or down regulation of a given responsive promoter, and identification of a substance which inhibits fungal cell growth, can be assayed using an array. For example, a cell comprising a responsive promoter/reporter hybrid or baseline promoter/reporter hybrid can be contacted with a substance to be tested for the ability inhibit fungal cell growth (to modulate an essential fungal gene). Promoter expression can then be assayed using conventional microarray assay techniques.

[0054] In one embodiment of the invention, a substance is determined to inhibit fungal cell growth (modulate the activity of an essential fungal gene) in a method as follows: (1) contacting a suitable fungal cell (e.g., an S. cerevisiae cell) with a substance to be tested for the ability to inhibit fungal cell growth (modulate an essential fungal gene) wherein said cell comprises one or more biomarkers operably linked to one or more reporter (e.g., the open reading frame which is located downstream of each biomarker promoter in a wild-type cell); (2) obtaining mRNA from the cell; (3) preparing labeled polynucleotides from the mRNA (e.g., comprising a radiolabel (e.g., .sup.32P, .sup.35S, .sup.14C, .sup.3H) or another suitable detectable label); (4) contacting the labeled polynucleotide with an array, which comprises one or more polynucleotides encoding said reporters (or oligonucleotide fragments thereof), under conditions sufficient for labeled mRNA to bind with corresponding polynucleotide probes on the array; (5) optionally removing unbound, labeled mRNA from the array; and (6) detecting bound, labeled mRNA.

[0055] The polynucleotide, in the array, can comprise a fragment of the reporter polynucleotide, for example 10, 20, 30 or more nucleotides thereof.

[0056] A "nucleic acid array", "array" or "matrix" refers to an array, including a microarray (see infra), containing nucleic acid probes, such as oligonucleotides or larger portions of genes. The nucleic acid on the array is preferably single stranded. Arrays wherein the probes are oligonucleotides are referred to as "oligonucleotide arrays" or "oligonucleotide chips." A "microarray", "biochip" or "biological chip" is an array of regions having a density of discrete regions of at least about 100/cm.sup.2, and preferably at least about 1000/cm.sup.2. The regions in a microarray have typical dimensions, e.g., diameters, in the range of between about 10-250 .mu.m, and are separated from other regions in the array by about the same distance.

[0057] The scope of the present invention includes an array (e.g., a microarray; discussed above) comprising one or more of said reporters (discussed above) which are operably linked to one or more of said biomarkers (discussed above).

[0058] Baseline promoters of the invention (e.g., SEQ ID NOs: 52-67 or a functional variant thereof) can also be used in assays for determining if a substance inhibits fungal cell growth and to calculate the inhibitory concentration (IC; e.g., IC50 or IC90) of a particular substance. Since baseline promoters generally exhibit a constant level of expression, they provide a convenient marker for overall cellular growth or cellular mass. Generally, baseline promoters can be used to determine the IC (e.g., IC50 or IC90) of a given substance in a method including the following steps: (a) introducing a hybrid comprising a baseline promoter selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043 W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter (e.g., SEQ ID NO: 52-67 or a functional variant thereof); operably linked to a reporter (e.g., SEQ ID NO: 42-51 or a functional variant thereof) into a suitable fungal cell; (b) contacting the cell with a substance to be tested for the ability to inhibit growth of the cell; (c) detecting signal from the reporter; and (d) selecting the substance if it causes a reduction in the signal from the reporter and/or calculating the IC (e.g., IC50 or IC90).

[0059] Optionally, this method can be performed with two or more different baseline promoter/reporter fusions (e.g., in a ratiometric assay discussed below). The IC (e.g., IC50 or IC90) can then be determined two or more times when each separate reporter is measured.

[0060] In an embodiment of the invention, a negative-control screening assay is also carried out. In this embodiment, a cell comprising the hybrid is contacted with the substance being tested and another, separate cell comprising the same hybrid is contacted with a blank (i.e., a substance known not to modulate the expression level from the first or second promoters) such as DMSO, water or buffer. If the substance being tested decreases the reporter signal in relation to the signal from the reporter in the cell contacted with the blank, this indicates that the substance is an anti-fungal substance. A positive-control screening assay may also be performed. In the positive-control assay, a cell comprising the hybrid is contacted with the substance being tested and another, separate cell comprising the same hybrid is contacted with a positive-control substance known to modulate the reporter signal (e.g., a known anti-fungal substance such as fluconazole, itraconazole, moconazole or terbinafine). If the substance being tested and the positive-control substance both decrease the reporter signal, this indicates that the substance being tested is an anti-fungal substance.

[0061] Baseline promoters of the invention (e.g., SEQ ID NOs: 52-67 or a functional variant thereof) can also be used in ratiometric assays, comprising two or more baseline promoters operably linked to two or more different reporters, for determining if a substance inhibits fungal cell growth and to calculate the inhibitory concentration (IC; e.g., IC50 or IC90) of a particular substance. For example, a ratiometric assay comprising use of a baseline promoter will comprise the steps of: (a) introducing two or more hybrids comprising two or more different baseline promoters selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter (e.g., SEQ ID NO: 52-67 or a functional variant thereof); operably linked to two or more different reporters (e.g., SEQ ID NO: 42-51 or a functional variant thereof) into a suitable fungal cell; (b) contacting the cell with a substance to be tested for the ability to inhibit growth of the cell; (c) detecting signal from the reporter; and (d) selecting the substance if it causes a reduction in the signal from the reporter and/or calculating the IC (e.g., IC50 or IC90). A range of several concentrations of a given substance can be assayed using this ratiometric method.

[0062] Ideally, the extent to which the reporter signal decreases, in response to any given concentration of a substance which is found to inhibit fungal cell growth, will be proportional (e.g., as compared to the promoter's expression level in the absence of any substance) to the extent to which the other reporter signals decrease in response to the same concentration of substance.

[0063] In an embodiment of the invention, a negative-control ratiometric screening assay is also carried out. In this embodiment, a cell comprising the first and second hybrid is contacted with the substance being tested and another, separate cell comprising the first and second hybrid is contacted with a blank (i.e., a substance known not to modulate the expression level from the first or second promoters) such as DMSO, water or buffer. If the substance being tested decreases the signal from the first and second reporters and if the blank fails to decrease the signal from the first and second reporters, this indicates that the substance is an anti-fungal substance. A positive-control ratiometic screening assay may also be performed. In the positive-control assay, a cell comprising the first and second hybrid is contacted with the substance being tested and another, separate cell comprising the first and second hybrid is contacted with a positive-control substance known to inhibit fungal growth (e.g., a known anti-fungal substance such as fluconazole, itraconazole, moconazole or terbinafine). If the substance being tested and the positive-control substance both decrease the signal from the first and second reporters, this indicates that the substance being tested is an anti-fungal substance.

[0064] Using two or more baseline promoters is advantageous because it facilitates elimination of false positives. For example, a false positive signal, suggesting that a substance being tested inhibits fungal cell growth, would occur if the substance causes a reduction in expression from the baseline promoter without inhibiting fungal cell growth. It is unlikely that the substance would have the ability to reduce baseline promoter expression, without reducing fungal cell growth (i.e., a false positive signal), with respect to two different baseline promoters.

[0065] The term "inhibitory concentration" or "IC" refers to the minimum concentration at which the substance being tested can inhibit the growth of the organism being tested. The term includes all inhibitory concentrations, for example, IC.sub.90 which is the inhibitor concentration needed to inhibit growth of 90% of the cells being tested and IC.sub.50 which is the inhibitor concentration needed to inhibit growth of 50% of the cells being tested. In an embodiment of the invention, a substance being tested for anti-fungal or anti-malignant cell growth activity is selected if it has a relatively low IC50 or IC90.

[0066] The present invention also includes compositions comprising any one of the isolated responsive promoters (e.g., SEQ ID NOs: 1-41 or 68 or a functional variant thereof) or baseline promoters identified herein (e.g., SEQ ID NOs: 52-67 or a functional variant thereof). Also included in the present invention is any of the isolated responsive promoters or baseline promoters identified herein fused to a reporter (e.g., a reporter gene including, but not limited to SEQ ID NOs: 42-51 or a functional variant thereof).

[0067] A responsive promoter/reporter gene hybrid and/or baseline promoter/reporter gene hybrid can be sustained in a host cell, in which a screening assay of the invention is performed, by any acceptable method known in the art. For example, the hybrid can be genetically integrated into the chromosome of the host cell or it can be maintained episomally, for example, in a plasmid (discussed above) or yeast artificial chromosome (YAC; discussed above) or other vector. In S. cerevisiae cells, for example, a hybrid can easily be integrated into the HO locus. Methods for constructing plasmids and vectors and for integrating a polynucleotide into a host cell chromosome are conventional and very well known in the art.

[0068] In another embodiment of the invention, anti-cancer agents can be identified using a responsive promoter of the invention. In particular, anti-cancer agents for treatment or prevention of cancer (e.g., by inhibiting growth of a malignant cell) in a mammal, preferably a human can be identified using a responsive promoter of the invention. For example, the S. cerevisiae YLR338W (SEQ ID NO: 22), S. cerevisiae YIL066W (SEQ ID NO: 23), S. cerevisiae YNL093W (SEQ ID NO: 24), S. cerevisiae YDR250C (SEQ ID NO: 8), S. cerevisiae YLR381W (SEQ ID NO: 25), S. cerevisiae YBL065W (SEQ ID NO: 68), S. cerevisiae YMR323W (SEQ ID NO: 38) and S. cerevisiae YPL171C (SEQ ID NO: 39) responsive promoters are particularly useful for identification of anti-cancer agents. These promoters have been found to modulate when genes in S. cerevisiae biochemical pathways and functions, that are homologous to human biochemical pathways and functions found to modulate the development of cancer (e.g., the mitotic cluster, including nucleocytoplasmic transport RAS, mitotic spindle, telomerase maintenance, DNA damage and G1 cell cycle control, establishment of cell polarity, exocyst complex and acetyltransferases). For example, the scope of the invention includes methods for identifying whether a substance can treat or prevent cancer in a mammal (e.g., by inhibiting growth of a malignant cell) comprising the following steps: (a) introducing a hybrid comprising a responsive promoter selected from the group consisting of S. cerevisiae YLR338W (SEQ ID NO: 22), S. cerevisiae YIL066W (SEQ ID NO: 23), S. cerevisiae YNL093W (SEQ ID NO: 24), S. cerevisiae YDR250C (SEQ ID NO: 8), S. cerevisiae YLR381W (SEQ ID NO: 25), S. cerevisiae YBL065W (SEQ ID NO: 68), S. cerevisiae YMR323W (SEQ ID NO: 38) and S. cerevisiae YPL171C (SEQ ID NO: 39) operably linked to a reporter (e.g., reporter gene such as SEQ ID NO: 42-51 or a functional variant thereof) into a suitable cell (e.g., a fugal cell); (b) contacting the cell with a substance to be tested for the ability to inhibit or prevent cancer; (c) detecting expression driven by the responsive promoter in the hybrid; (d) selecting the substance if it modulates expression from the responsive promoter.

[0069] The present invention also includes a ratiometric screening assay wherein a responsive promoter of the present invention is used to identify a substance that can treat or prevent cancer in a mammal (e.g., by inhibiting growth of a malignant cell) comprising the following steps: (a) introducing, into a suitable fungal cell, a first hybrid comprising a first (gene responsive) promoter selected from the group consisting of: S. cerevisiae YLR338W (SEQ ID NO: 22), S. cerevisiae YIL066W (SEQ ID NO: 23), S. cerevisiae YNL093W (SEQ ID NO: 24), S. cerevisiae YDR250C (SEQ ID NO: 8), S. cerevisiae YLR381W (SEQ ID NO: 25), S. cerevisiae YBL065W (SEQ ID NO: 68), S. cerevisiae YMR323W (SEQ ID NO: 38) and S. cerevisiae YPL171C (SEQ ID NO: 39); operably linked to a first reporter (e.g., SEQ ID NO: 42-51 or a functional variant thereof); and a second hybrid comprising a second (baseline promoter) selected from the group consisting of: S. cerevisiae YHR082C Promoter, S. cerevisiae YDL126C Promoter S. cerevisiae YBR106W Promoter, S. cerevisiae YLL043W Promoter, S. cerevisiae YPR108W Promoter, S. cerevisiae YIL041W Promoter, S. cerevisiae YJL166W Promoter S. cerevisiae YDR165W Promoter, S. cerevisiae YLR330 W Promoter, S. cerevisiae YDL058W Promoter, S. cerevisiae YHR012W Promoter, S. cerevisiae YKL053W Promoter, S. cerevisiae YKL196C Promoter, S. cerevisiae YDL103C Promoter S. cerevisiae YLR427W Promoter and S. cerevisiae YLL020C Promoter (e.g., SEQ ID NO: 52-67 or a functional variant thereof); operably linked to a second reporter (e.g., SEQ ID NO: 42-51 or a functional variant thereof); (b) contacting the cell with a substance to be tested for the ability to treat or prevent cancer; (c) detecting expression driven by the first and second promoters; and (d) selecting the substance if it causes the expression level from the first (gene responsive) promoter to increase or decrease in relation to the expression level from the second (baseline) promoter.

[0070] In an embodiment of the invention, a negative-control ratiometric screening assay is also carried out. In this embodiment, a cell comprising the first and second hybrid is contacted with the substance being tested and another, separate cell comprising the first and second hybrid is contacted with a blank (i.e., a substance known not to modulate the expression level from the first or second promoters) such as DMSO, water or buffer. If the substance being tested increases or decreases the expression level from the first promoter/reporter in relation to the second promoter/reporter and if the blank fails to increase or decrease the expression level from the first promoter/reporter in relation to the second promoter/reporter, this indicates that the substance does modulate the expression level from the responsive promoter, and, that it does modulate the activity of the fungal gene (i.e., the substance is an anti-cancer substance). A positive-control ratiometic screening assay may also be performed. In the positive-control assay, a cell comprising the first and second hybrid is contacted with the substance being tested and another, separate cell comprising the first and second hybrid is contacted with a positive-control substance known to modulate the expression level from the first promoter/reporter in relation to the expression level from the second promoter/reporter. If the substance being tested and the positive-control substance both modulate the expression level from the first promoter/reporter in relation to the expression level from the second promoter/reporter, this indicates that the substance being tested does modulates the expression level from the responsive promoter/reporter, and, that it does modulate the activity of the essential fungal gene (i.e., the substance is an anti-cancer substance).

Reporters

[0071] One embodiment of the invention includes a responsive promoter of the invention (e.g., SEQ ID NOs: 1-41 or 68 or a functional variant thereof) or baseline promoter of the invention (e.g., SEQ ID NOs: 52-67 or a functional variant thereof) fused to a reporter. Any suitable reporter may be fused to the responsive promoter or baseline promoter. A "reporter" is any polynucleic acid which can be detected when expressed from a promoter. The term includes reporter genes whose activity can be detected as well as polynucleic acids which can be detected directly, for example, by northern blot analysis. Alternatively, the translated protein product of the expressed polynucleic acid can be detected by western blot analysis. For example, the term "reporter" includes the genetic sequence which is down-stream of a given responsive promoter on a wild-type yeast chromosome. Reporters include luminescent and fluorescent reporter genes including, but not limited to, green fluorescent protein (e.g., SEQ ID NO: 48), lacZ (e.g., SEQ ID NO: 51), Renilla luciferase (e.g., SEQ ID NO: 49; see also Genbank Accession Nos.: AF416990; AR149562; AF362548 or M63501) firefly (Photinus pyralis) luciferase (e.g., SEQ ID NO: 50; see also Genbank Accession Nos.: U03687; M15077 and X84846), S. cerevisiae ADE2 (e.g., SEQ ID NO: 42), S. cerevisiae LYS2 (e.g., SEQ ID NO: 43), S. cerevisiae TRP1 (e.g., SEQ ID NO: 44), S. cerevisiae LEU2 (e.g., SEQ ID NO: 45), S. cerevisiae URA3 (e.g., SEQ ID NO: 46) and S. cerevisiae HIS3 (e.g., SEQ ID NO: 47).

[0072] The term "signal", in relation to a reporter, refers to the indicia of expression of the reporter or the presence of the reporter's gene product (e.g., protein or mRNA) in a sample. For example, fluorescence is a signal that indicates the presence of green fluorescent protein (GFP) and a "band" on photographic film generated during a northern blot procedure is a signal indicating the presence of a gene's RNA transcript. In an embodiment of the invention, the expression driven from a given promoter fused to a given reporter is measured by determining the signal from the reporter.

[0073] Firefly luciferase may also be altered as described in Leskinen et al. (Yeast. 20(13):1109-1113 (2003)) wherein the carboxy-terminal peroxisomal targeting signal, Ser-Lys-Leu (slk), of the firefly luciferase gene was removed; this allowed luciferase activity to be detected in whole S. cerevisiae cells.

[0074] Other versions of luciferase which may be fused to a responsive promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof) include the Vibrio harveyi luxA (Genbank Accession No. M10961) and Vibrio harveyi luxB (Genbank Accession No. M10961.1) genes, together, unfused or fused (i.e., luxAB or luxBA), Vibrio harveyi luxC, Vibrio harveyi luxD, Vibrio harveyi luxE, Vibrio harveyi luxCDABE, the Photorhabdus luminescens LuxCDABE operon (Genbank Accession No. M62917), Photorhabdus luminescens LuxA, Photorhabdus luminescens LuxB, Photorhabdus luminescens LuxC, Photorhabdus luminescens LuxD, Photorhabdus luminescens LuxE, optionally expressed in the presence of the Vibrio fischeri flavin oxidoreductase gene (frp; see Gupta et al., FEMS Yeast Res. 4(3):305-13 (2003)); Vibrio fischeri luxAB (see, e.g., Yang et al., FEMS Microb. Lett. 176(1): 57-65 (1999)), the Vibrio fischeri LuxCDABE operon (see e.g., Van Dyk et al., Appl. Environ. Microbiol. 60:1414-1420 (1994); Belkin et al., Appl. Environ. Microbiol. 62:2252-2256 (1996); Belkin et al., Water Res. 31:3009-3016 (1997); Genbank Accession No. AF170104); Vibrio fischeri luxA, Vibrio fischeri luxB, Vibrio fischeri luxC, Vibrio fischeri luxD or Vibrio fischeri luxE. Furthermore, a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41 or 68 or a functional variant thereof) can be fused to a green fluorescent protein (GFP)-luxAB hybrid gene.

[0075] The Ca.sup.2+ dependent photoprotein Aequorin from Aequorea victoria (Campbell, K., Chemilluminescence; Ellis Horwood: Chichester, England (1988); Ramanathan et al., Anal. Chim. Acta 369: 181-188 (1998); Witkowski et al., Anal. Chem. 66: 1837-1840 (1994); Galvan et al., Anal. Chem. 68:3545-3550 (1996)) can also be fused to a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof).

[0076] The KanMX selectable marker (e.g., from Tn903) can also be fused to a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof). Expression of the KanMX marker, in a cell, confers resistance to G418 (geniticin; Wach et al., Yeast 10:1793-1808 (1994)).

[0077] The pat1 (phosphinothricin N-acetyl-transferase) selectable marker can also be fused to a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof; Goldstein & McCusker, Yeast 15:1541-1553 (1999)). Expression of the pat1 marker, in a cell, confers resistance to bialaphos.

[0078] The nat1 (nourseothricin N-acetyl-transferase) selectable marker can also be fused to a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof; Goldstein & McCusker, Yeast 15:1541-1553 (1999)). Expression of the nat1 marker, in a cell, confers resistance to nourseothricin.

[0079] The hph (hygromycin B phosphotransferase) selectable marker can also be fused to a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof; Goldstein & McCusker, Yeast 15:1541-1553 (1999)). Expression of the nat1 marker, in a cell, confers resistance to hygromycin B.

[0080] The Sh ble selectable marker can also be fused to a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof). Expression of the Sh ble marker, in a cell, confers resistance to Zeocin.TM. (Phleomycin D1; Johansson & Hahn-Hagerdal, Yeast 19: 225-231 (2002)).

[0081] Other reporter genes which may be fused to a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof) include .beta.-lactamase, for example, as described in Cartwright et al. (Yeast 10(4):497-508 (1994)) wherein mature .beta.-lactamase was fused to two segments of the K1 preprotoxin.

[0082] Furthermore, the E. coli .beta.-glucuronidase gene (GUS) can be fused to a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof) and used as a reporter gene, for example, in S. cerevisiae (Marathe et al., Gene. 154(1):105-107 (1995)).

[0083] Chloramphenicol acetyltransferase (CAT) can be fused to a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof). CAT radioassays are described, for example, by Sleigh (Anal. Biochem. 156(1):251-256 (1986)) and a non-radioactive CAT assay is described by Young et al. (Anal. Biochem. 197(2):401-407 (1991)).

[0084] Construction of responsive promoter/reporter fusions and baseline promoter/reporter fusions can be accomplished using conventional molecular biological techniques which are commonly known in the art. For example, Myers et al. (Gene. 1986; 45(3):299-310) disclose methods for fusing various promoters for driving the expression of the E. coli lacZ gene.

[0085] Expression of reporters, such as green fluorescent protein, luciferase or .beta.-galactosidase (lacZ) or any other reporter mentioned herein, can be easily determined using any of the numerous assays which are conventional and very well known in the art. For example, Billinton et al. (Biosens. Bioelectron. 13(7-8): 831-8) describe the development of a green fluorescent protein reporter in yeast. Dixon et al. (J. Steroid Biochem. Mol. Biol. 62(2-3): 165-71) describe an assay for determination of lacZ expression in yeast. El Barkani et al. (Gene 246(1-2): 151-155 (2000)) describe Candida glabrata shuttle vectors suitable for translational fusions to lacZ and use of .beta.-galactosidase as a reporter of gene expression." Greer et al. (Luminescence 17(1): 43-74 (2002)) reviews the use of luciferase in expression assays. Leskinen et al. (Yeast 20(13): 1109-13 (2003)) describes a one-step measurement of firefly luciferase activity in yeast. Marathe et al. (Gene 154(1): 105-7 (1995)) and Gallagher et al. ("Quantiation of GUS activity by fluorometry" In: GUS Protocols: Using GUS gene as a reporter of gene expression. Academic Press, San Diego, Calif. (1992), pp. 47-59) discloses methods for assaying GUS reporter gene expression. Pignatelli et al. (Biotechnol. Appl. Biochem. 27(Pt2): 81-88 (1998)) describe the expression and secretion of .beta.-galactosidase in Saccharomyces cerevisiae using the signal sequences of GgpI. Srikantha et al. (J Bacteriol 178(1): 121-9 (1996)) describes the use of Renilla reniformis luciferase as a reporter gene in Candida albicans. Vanoni et al. (Biochem Biophys Res Commun 164(3): 1331-8 (1989)) describes the use of E. coli .beta.-galactosidase in Saccharomyces cerevisiae using the signal sequence from the glucoamylase-encoding STA2 gene.

[0086] Alternatively, there are several auxotrophic reporters which may be fused to a responsive promoter or baseline promoter of the invention (e.g., SEQ ID NOs: 1-41, 52-68 or a functional variant thereof). For example, ADE2, URA3, HIS3, LYS2, TRP1 or LEU2 can be fused to the responsive promoter and introduced into a cell lacking an endogenous copy of the gene (e.g., comprising a ura3-52, his3-D1, leu2-D1, trp1-D1 or lys2-201 mutation). In general activation of auxotrophic reporter genes can be determined, in a cell lacking an endogenous copy of the auxotrophic marker, by growing the cell on media lacking the nutrient whose cellular synthesis is dependent on the auxotrophic reporter gene. In this case, lack of expression of the auxotrophic marker (e.g., because of lack of activation of the responsive promoter-auxotrophic marker hybrid) will result in no growth; expression of the auxotrophic marker (e.g., because of activation of the responsive promoter-auxotrophic marker hybrid) will result in growth. For example, activation of the markers ADE2, URA3, HIS3, LYS2, TRP1 or LEU2 can be assayed on media lacking adenine, uracil, histidine, lysine, tryptophan or leucine, respectively. In another embodiment, expression of ADE2 can be conveniently determined by observing the color of S. cerevisiae colonies containing the responsive promoter-ADE2 hybrid. Specifically, ade2.sup.- S. cerevisiae cells and colonies exhibit a red color phenotype. Expression of ADE2 (e.g., because of activation of the responsive promoter-ADE2 hybrid), in such a cell, will result in the expression of a white color phenotype.

[0087] In an embodiment of the present invention, substances which lead to a decrease in the expression level from a responsive promoter of the invention can be negatively selected for. For example, cell grown in the present of substance that decreases the expression from a responsive promoter/URA3 hybrid can be selected for by growth in the presence of 5-fluoroorotic acid (5-FOA). In other embodiments of the invention, cells in which responsive promoter/HIS3 hybrid expression is decreased, in response to a substance, can be selected for by growing the cells in the presence of 3-azatriazole. In yet another embodiment of the invention, cells in which responsive promoter/LYS2 hybrid expression is decreased, in response to a substance, can be selected for by growing the cells in the presence of DL-alpha-aminoadipic acid. In a further embodiment of the invention, cells in which responsive promoter/CYH2 hybrid expression is decreased, in response to a substance, can be selected for by growing the cells in the presence of cycloheximide. In another embodiment of the invention, cells in which responsive promoter/CAN/hybrid expression is decreased, in response to a substance, can be selected for by growing the cells in the presence of canavinine.

Transformation and Growth of Fungal Cells

[0088] Heterologous nucleic acids can be introduced into host yeast cells by any of a number of known methods. These methods include, but are not limited to, spheroplast transformation (Beggs, Nature 275:104 (1975); Cregg et al., Mol. Cell. Biol. 5:3376 (1985)), lithium transformation (Hiep et al., Yeast 9:1189-1197 (1993); Bogdanova et al., Yeast 11:343 (1995)), polyethylene glycol transformation (Kleve et al., Gene 25:333-341 (1983); Dohmen et al., Yeast 7:691-692 (1991); Dohmen et al., Yeast 7:691-692 (1991)), or electroporation.

[0089] Yeast can be grown on rich media or synthetic dropout media. Drop-out media is synthetic media containing all essential nutrients except for one or more. Drop-out media is commonly used for selection of plasmids that contain genes for synthesis of these components. For example, drop-out media lacking histidine can be used to select for his3.sup.- host cells containing a plasmid carrying a complementing HIS3 gene. A similar method can be employed for selecting for fungal cells carrying a plasmid containing the ADE2, URA3, LYS2, TRP1 or LEU2 gene, or any combination thereof. For example, one liter of synthetic complete media (with no nutrients dropped out) includes 20 g dextrose, 6.7 g yeast nitrogen base without amino acids and 0.79 g Complete Supplement Mixture CSM (Adenine 10 mg/liter; Arginine 50 mg/liter; Aspartic Acid 80 mg/liter; Histidine 20 mg/liter; Isoleucine 50 mg/liter; Leucine 100 mg/liter; Lysine 50 mg/liter; Methionine 20 mg/liter; Phenylalanine 50 mg/liter; Threonine 100 mg/liter; Tryptophan 50 mg/liter; Tyrosine 50 mg/liter; Uracil 20 mg/liter; Valine 140 mg/liter; Qbiogene; Carlsbad, Calif.). A commonly used "rich media" is YPD (Yeast-Peptone-Dextrose) or 1% yeast extract, 2% peptone, 2% dextrose. For solid media, 2% agar is included.

EXAMPLES

[0090] The following examples are provided to more clearly describe the present invention and should not be construed to limit the scope of the invention in any way. Any and all reagents (e.g., plasmids, primers, cells) described herein form part of the present invention along with any methods described herein.

Example 1

Identification of Biomarkers

[0091] In this example, genes identified by "Affymetrix Microarray" (Affymetrix, Inc.; Santa Clara, Calif.) technology are used as biomarkers to identify compounds that affect a target protein. By fusing a biomarker promoter to a reporter gene, assays can be developed to screen for antifungal compounds. In addition, several "baseline promoters" have been identified which exhibit a constant level of expression when temperature is shifted.

[0092] Yeast temperature-sensitive shift. Saccharomyces cerevisiae strains were grown at 30.degree. C. in YPD (1% yeast extract, 2% peptone, 2% glucose). S. cerevisiae wild type WT1554 and ts-mutant strains were streaked out from permanent stock and grown on YPD plates (including 2% agar) at 30.degree. C. until colonies formed. Several colonies were picked to start 10 ml cultures, grown up overnight at 30.degree. C. and used to inoculate 25 mls of 30.degree. C. YPD to an OD of 0.15. Cultures were incubated at 30.degree. C. for 2 hrs and then heat shifted to 37.degree. C. by the addition of 25 mls of 46.degree. C. YPD. Strains were grown for 2 hr, 4 hr, 6 hrs and cells were collected for determination of Affymetrix Microarray expression profiles. Cells were harvested by centrifugation for 3 minutes at 3500 rpm, resuspend in 6 ml of ice cold ddH.sub.2O centrifuged for 3 minutes at 3500 rpm, the supernatant discarded and the cell pellet flash frozen in a dry ice ethanol bath. Pellets were stored at -80.degree. C. until total RNA preparation.

[0093] Isolation of Saccharomyces cerevisiae total RNA. Total RNA was isolated with slight modifications by the method of Schmitt et al. (Nucleic Acids Res. 18(10):3091-3092 (1990)). Cell pellets were removed from the -80.degree. C. freezer and 1.6 ml of pre-warmed 65.degree. C. acid phenol-chloroform-isoamylalcohol (50:50:1, pH4.7; (Sigma P-1944) and 1.6 ml of TES (10 mM Tris pH 7.5, 10 mM EDTA, 0.5% SDS) were added and the pellet was resuspended by vortexing. Tubes were incubated at 65.degree. C. in a waterbath for 1 hour with vortexing for 20 seconds every 10 minutes. The mixture was transferred to Phaselock tubes (Eppendorf) and centrifuged for 20 minutes at room temperature. Mixtures were re-extracted with 750 .mu.l of acid phenol-chloroform-isoamylalcohol per tube, recentrifuged then extracted with 750 .mu.l 24:1 chloroform:Isoamyl alcohol (Sigma C-0549) and centrifuged for 10 minutes room temperature. The aqueous phase was transferred to an eppendorf tube and total RNA was precipitated by the addition of 50 .mu.l of 3M Sodium acetate (NaOAc) pH 5.2 and 1 ml of 100% EtOH followed by incubation at -20.degree. C. for 1/2 hr. Total RNA pellets were washed with 500 .mu.l of 80% ETOH and the pellet was resuspended in 50 .mu.l of 65.degree. C. RNAsecure (Ambion; Austin, Tex.) and incubated for 10 min at 65.degree. C. to inactivate RNAses. Total RNA quality and quantity was determined by measurement of the OD.sub.260/OD.sub.280 absorbance ratio followed by analysis of RNA utilizing Agilent RNA chips. RNA was stored at -80.degree. C. prior to Affymetrix labeling and hybridization.

[0094] Affymetrix total RNA labeling and Affymetrix Yeast Genome YG_S98 microarray probing. Polynucleotide Expression Profiling. Total S. cerevisiae RNA from each RNA sample (see supra) was used to prepare biotinylated target RNA according to the Affymetrix Genechip.RTM. Expression Analysis Technical Manual, 2003. http://www.affymetrix.com/support/technical/anual/manual/expression_manua- l.affx). Briefly, 5 .mu.g of total RNA was used to generate first-strand cDNA by using a T7-linked oligo(dT) primer. After second-strand synthesis probes were generated by in vitro transcription with biotinylated UTP and CTP (Enzo Diagnostics). Biotinylated probes were hybridized to Affymetrix Yeast YG_S98 DNA Microarrays (Affymetrix Inc., Santa Clara, Calif.). Target cDNA generated from each sample were then processed according to the manufacturer's recommended procedures using an Affymetrix GeneChip Instrument System (http://www.affymetrix.com/support/technical/manual/expression_manual.aff- x). Briefly, spike controls were added to 5 .mu.g fragmented cRNA before overnight hybridization to Affymetrix Yeast Genome YG_S98 microarrays. Microarrays were then washed and stained with streptavidin-phycoerythrin, before being scanned on an Affymetrix GeneChip scanner. The GeneChip.RTM. Yeast Genome YG_S98 Array contains probe sets for approximately 6,400 S. cerevisiae (S288C strain) genes identified in the Saccharomyces Genome Database. This array also contains approximately 600 additional probe sets representing putative open reading frames (ORFs) identified by SAGE analysis, mitochondrial proteins, TY proteins, plasmids, and a small number of ORFs for strains other than S288C (Affymetrix Santa Clara, Calif.). Scanned image files were inspected for artifacts and analyzed with GeneChip.RTM. Expression Analysis software (Affymetrix, Santa Clara, Calif.). Each chip was scaled to 150 (see, Affymetrix, Genechip.RTM. Expression Analysis Technical Manual, 2003) to account for minor differences in microarray hybridization intensity, so that overall expression levels for each yeast strain could be compared.

[0095] Identification of up-regulated gene biomarkers in heat shifted S. cerevisiae ts-alleles by analysis of Affymetrix microarrays by GeneSpring analysis software (Silicon Genetics). Affymetrix Yeast Genome YG_S98 microarray data were loaded onto the GeneSpring analysis software program 6.0 (Silicon Genetics, Redwood City, Calif.). Microarray data from temperature shifted S. cerevisiae ts-alleles from the 2, 4, and 6 hr time-points (see supra) were normalized to S. cerevisiae wild type strain MS1554 from 2, 4, and 6 hr time-points. Up-regulated gene biomarkers were identified in S. cerevisiae ts-alleles that showed a fold increase in expression at a single time-point as compared to wild-type S. cerevisiae strain MS1554. Data were further analyzed to identify up-regulated gene biomarkers that showed up-regulation in expression at 2, 4, and 6 hr time-points by graphical analysis of identified genes. In addition genes that showed up-regulation in expression were analyzed in all ts-alleles to identify genes that were uniquely up-regulated in expression in a single ts-allele or up-regulated in a group of ts-alleles.

Plasmids and Constructs

(a) Generation PHO5 Signal Sequence Tagged Renilla luciferase

[0096] pSPRT17 (Cyc1A term to HO-poly-HO vector). The cyclA terminator (REF) was PCR amplified as a 371 by fragment from pYES2 (Invitrogen) using PCR primers PR131 (5' tttgcgcgcGGGCCGCATCATGTAATTAGT 3') (SEQ ID NO: 69) and PR132 (5' aaaagatctGACCGA GCGCAGCGAGTCAGT 3') (SEQ ID NO: 70) designed to BssHII and BglII. and cloned into the TOPO-TA to yield pSPRT19. The 371 by fragment from pSPRT19 was ligated to BssHII and BglII. digested HO-poly-HO (Voth et al., Nuc. Acid Res. 29(12): e59 (2001)) to yield pSPRT17.

[0097] pSPRT47 (SEQ ID NO: 85) (Renilla cloned into pSPRT17). The renilla luciferase gene was amplified by PCR as a 1004 by fragment amplified from phRG-B (Promega) using primers PR161 (5' CCCATGTTAATTAAATCTGTTGTTTATTCAATTTTAGCCGCTTCTTTGGCCAATGCAGGTGCTTCCAAGGTGT- ACGACCCCGA 3') (SEQ ID NO: 71) and PR162 (5' AAAGGCGCGCCTTACTGCTCGTTCTTCAGCAC 3') (SEQ ID NO: 72), designed to contain the PHO5 signal sequence (MLIKSVVYSILAASLANAG) (SEQ ID NO: 73) and PacI/AscI ends. cloned into the TOPO-TA to yield pSPRT27. The PacI/AscI fragment from pSPRT27 was ligated to PacI/BssHII digested pSPRT17 to yield pSPRT47. The Pad site was designed to create an ATG start codon fusion with Pad adapted promoters. This added LI to the signal sequence. The PHO5 tagged luciferase was designated PHO5.hRluc.

[0098] pSPRT168 (Gall promoter PHO5.hRluc). The GAL1 promoter region was PCR amplified as a BamHI/PacI 474 by fragment using PCR primers PR172 (5'TTTGGATCCACGGATTAGAAGCCGCCGAGCG 3') (SEQ ID NO: 74) and PR 173B (5' CCCTTAATTAACATGGTTTTTTCTCCTTGACGTTA 3') (SEQ ID NO: 75) cloned into the TOPO-TA to yield pSPRT33B. The BamHI/PacI fragment was ligated to BamHI/PacI digested pSPRT47 to yield pSPRT167. pSPRT167 was introduced into S. cerevisiae to yield strain Y167.

[0099] pSPRT207 (YHR082C promoter PHO5.hRluc). The YHR082C promoter was PCR amplified as a 1.1 kb BamHI/PacI fragment using PCR primers PR207 (5' TTTGGATCCTGTGCACGATGGCTTCGTTTTAGCC 3') (SEQ ID NO: 76) and PR208 (5' CTTAATTAACATCGAGTTTCAAAAAATTGTAAG 3') (SEQ ID NO: 77) and cloned into the TOPO-TA to yield pTOPO207. The 1.1 kb BamHI/PacI fragment from pSPRT207TOPO was ligated to BamHI/PacI digested pSPRT47 to yield pSPRT207. pSPRT207 was introduced into S. cerevisiae to yield strain Y207.

[0100] pSPRT211 (ERG10 promoter PHO5.hRluc). The ERG10 promoter was PCR amplified as a 397 bp BamHI/PacI fragment using PCR primers PR213 (5' CCCGGATCCTCTACGATATATCCTGTAAATAG 3') (SEQ ID NO: 78) and PR214 (5' CTTAATTAACATTTTGAGTACGTCTAATCTGTAT 3') (SEQ ID NO: 79) and cloned into the TOPO-TA to yield pTOPO211. The 397 by BamHI/PacI fragment from pSPRT213TOPO was ligated to BamHI/PacI digested pSPRT47 to yield pSPRT211. pSPRT211 was introduced into S. cerevisiae to yield strain Y211.

(b) Generation PHO5 Signal Sequence Tagged FireFly Luciferase

[0101] pSPRT50 (SEQ ID NO: 86) (Firefly luciferase cloned into pSPRT17). The firefly luciferase gene was PCR as a 1710 by fragment amplified from pGL2-Basic (Promega; Madison, Wis.) using primers PR167 (5' CCCATGGGATCCAAATCTGTTGTTTATTCAATTTTA GCCGCTTCTTTGGCCAATGCAGGTGAAGACGCCAAAAACATAAAGAAA 3') (SEQ ID NO: 80) and PR168SLK (5'AAAGGCGCGCCTTACTTTCCGCCCTTCTTGGCCT 3') (SEQ ID NO: 81), designed to contain the PHO5 signal sequence (MLIKSVVYSILAASLANAG) (SEQ ID NO: 82) and BamHI/AscI ends and remove the C-terminal SLK peroxisomal targeting sequence (Leskinen et al., Yeast 20(13):1109-1113 (2003)). This fragment was cloned into the TOPO-TA to yield pSPRT50. The BamHI/AscI fragment from pSPRT50 was ligated to BamHI/BssHII digested pSPRT17 to yield pSPRT50. The BamHI site was designed to create an ATG start codon fusion with BamHI adapted promoters. The PHO5 tagged firefly luciferase was designated PHO5.firefly.

[0102] pSPRT170 (Gall promoter PHO5.firefly). The Galp1 promoter region was PCR amplified as a BamHI 472 by fragment using PCR primers PR174 (5'TTTGGATCCACGGATTAGAAGCCGCCGAGCG 3') (SEQ ID NO: 83) and PR175B (5' TTTGGATCCCATGGTTTTTTCTCCTTGACGTTA 3') (SEQ ID NO: 84) cloned into the TOPO-TA to yield pTOPO174. The BamHI fragment was ligated to BamHI digested pSPRT50 to yield pSPRT170. pSPRT170 was introduced into S. cerevisiae to yield strain Y170.

TABLE-US-00002 TABLE 2 Biomarkers identified. Fold Essential 2, 4, or Gene Function Affy ID 6 hr RP Synonym Function YCR052W Chromatin 8141_AT 15 YOR387C remodeling complex YBR156C Mitotic spindle protein 8141_AT 5 YOR387C YDR166C Exocyst complex 9445_AT 13 YMR175W SIP18 Salt induced protein YDR166C Exocyst complex 5323_AT YFR026C YDR166C Exocyst complex 11185_AT 17 YJL153C INO1 L-myo-inositol-1-phosphate synthase YKR025W RNA polymerase III 7810_AT 9.2 YPL033C subunit YKR025W RNA polymerase III 8593_AT 7.0 YOL058W ARG1 Arginosuccinate synthetase subunit YDL105W 8276_AT 25 YOR255W YDL105W 6215_AT 14 YDR250C YDL105W 6007_AT 9 YDR446W ECM11 ExtraCellular Mutant YDL105W 5915_AT 8 YDR536W STL1 sugar transporter-like protein YDR016C spindle integrit, 8276_AT 16 YOR255W kinetochore YDR016C spindle integrit, 6710_AT 9 YDL243C AAD4 Putative aryl-alcohol dehydrogenase kinetochore YDR016C spindle integrit, 6221_AT 9 YDR256C CTA1 Catalase A kinetochore YDR016C spindle integrit, 6215_AT 9 YDR250C kinetochore YDR016C spindle integrit, 6007_AT 11 YDR446W ECM11 posible chromatin structure maint kinetochore YDR016C spindle integrit, 5915_AT 10 YDR536W STL1 sugar transporter-like protein kinetochore YNL131W Translocase 5410_F_AT 5.115 YFL020C PAU5 member of the seripauperin Mitochondrial proteinVgene family (see Gene_class membrane PAU) YDR464W Control expression of 7953_AT 5.8 YPL205C spliceosome YPL128C TTAGGG repeat 5220_AT 13.5 YGL205W POX1 fatty-acyl coenzyme A oxidase binding factor YLR291C Translational initiation 5125_AT 8.9 YGL117W factor YLR291C Translational initiation 4503_AT 8.4 YHR029C factor YLR291C Translational initiation 9771_AT 5.8 YML116W ATR1 predicted protein is very hydrophobic, factor has many membrane-spanning regions, several potential glycosylation sites, potential ATP-binding site YLR291C Translational initiation 10902_AT 5.4 YJR109C CPA2 carbamyl phosphate synthetase factor YLR291C Translational initiation 6902_AT 5.3 YCL030C HIS4 histidinol dehydrogenase factor YLR293C Nuclear organization 10008_AT 71.13 YLR338W YLR293C Nuclear organization 4039_AT 38.90 YIL066W-A RNR3 Ribonucleotide reductase YLR293C Nuclear organization 8939_AT 32.54 YNL093W YPT53 rab5-like GTPase YLR293C Nuclear organization 6215_AT 25.45 YDR250C YLR293C Nuclear organization 9962_AT 12.40 YLR381W Kinetochore protein YLR293C Nuclear organization 10714_AT 10.96 YKL159C Regulator of calcineurnin YLR293C Nuclear organization 4159_AT 10.96 YIL058W YLR293C Nuclear organization 10554_AT 9.85 YKR037C Spindle pole component YDR499W Telomere Checkpoint 10008_AT 125.0 YLR338W YDR499W Telomere Checkpoint 6215_AT 43.4 YDR250C YDR499W Telomere Checkpoint 4039_AT 42.8 YIL066W-A RNR3 Ribonucleotide reductase YDR499W Telomere Checkpoint 9160_AT 28.9 YNL279W Pheromone-regulated multispanning YDR499W Telomere Checkpoint 8939_AT 22.2 YNL093W YPT53 rab5-like GTPase sorting and endocytosis YDR499W Telomere Checkpoint 9962_AT 15.3 YLR381W Kinetochore protein YDR499W Telomere Checkpoint 10554_AT 9.7 YKR037C Spindle pole component YDR499W Telomere Checkpoint 8505_AT 9.6 YOR032C HMS1 myc-family transcription factor homolog YBR102C exocyst complex 10008_AT 109.7 YLR338W YBR102C exocyst complex 9160_AT 58.7 YNL279W Pheromone-regulated multispanning YBR102C exocyst complex 6215_AT 53.7 YDR250C YBR102C exocyst complex 4039_AT 37.5 YIL066W-A RNR3 Ribonucleotide reductase YBR102C exocyst complex 8939_AT 27.6 YNL093W YPT53 rab5-like GTPase YGL225W May regulate Golgi 9293_AT 6.3 YML058W SML1 Suppressor of mec lethality function YGR065C Vitamin H transporter 9309_AT 5.49 YMR303C ADH2 alcohol dehydrogenase II YML091C Mitochondrial RNase P 11185_AT 23.0 YJL153C INO1 L-myo-inositol-1-phosphate synthase YML091C Mitochondrial RNase P 10256_AT 16.2 YLR092W SUL2 high affinity sulfate permease YML091C Mitochondrial RNase P 5428_AT 15.8 YFL052W YML091C Mitochondrial RNase P 4098_AT 5.2 YIR017C MET28 Transcriptional activator of sulfur amino acid metabolism YML091C Mitochondrial RNase P 10414_AT 4.2 YLL062C YDR081C Regulates trans of 10008_AT 112 YLR338W PDC1, PDC5 YDR081C Regulates trans of 6215_AT 42 YDR250C PDC1, PDC5 YDR081C Regulates trans of 4039_AT 35 YIL066W RNR3 Ribonucleotide reductase subunit PDC1, PDC5 YDR081C Regulates trans of 8939_AT 21 YNL093W YPT53 rab5-like GTPase PDC1, PDC5 YMR033W Transcriptional 10008_AT 57 YLR338W regulation YMR033W Transcriptional 6215_AT 34 YDR250C regulation YMR033W Transcriptional 4039_AT 22 YIL066W-A RNR3 Ribonucleotide reductase subunit regulation YMR033W Transcriptional 9288_S_AT 19.6 YMR323W regulation YMR033W Transcriptional 7944_AT 12 YPL171C OYE3 DAD(P)H dehydrogenase regulation YMR033W Transcriptional 5636_AT 9 YER065C ICL1 Isocitrate lyase regulation YMR033W Transcriptional 6349_AT 9 YDR114C regulation

[0103] Responsive promoters identified in the experiments set forth above are as follows:

TABLE-US-00003 >YOR387C Chr 15 reverse complement (SEQ ID NO: 1) GCCAGGGAAGCCTATATCTGATTCCCTGTTTCATAATCCAATGCAG CCACTAGCTTATAATTATTTGAACTATTTGTCGAACATCACAGTAA TAAAATCCCCAGAAAGTTCCACTTGCTGCATATTGGCACCTGTTGA TTCACTCTCCATCACTTTTTTGTTAGCCGCCCAGCCTAGAAAGTCT TTAAATACATCTGAAATTTTTTTTTTTTTAACAGTGCACCCGTGCA TCATACCTCATGCAAGGTACCTTTTTTTCTCAAAGGTATTGTCTTC CATTGAAGTGGCACTATGGCATGATGAACCCTGAGCATTTCTGAAT TCAACAGAACCAAATTGTCCAGAAATAAATCTGTCCGACATGAATT ATGAAACTTTTTTTCAATTAAGTGAAGAGAATTTTGCAGCGTCTTA CCATTATTTTGACCCATTGGTCGCATGTTTGCGCTTTGACTTCGAG AACCATGTTAAAGCTTACTTGTACGACAACCAATGAAGTATATTAC GGCAGTTTTTTTGGACTGGGTCAAAAAAAGTGTTGCATAATCAAAT CAGGAACACATTAAAATGTTGTAAAATTTGTCTTAGTATCACCTGA GTGGTTATTCATTACGTACTACTGTCAAAATATTCGGATCTTTCCT AAACGGGCTTTTGAATTAGTGTTGCTTCTATTCCTGGAATGGAAGG TAATACTTTCATGCATTCTCGCTTTTCGGACTTTTAACAATAAATT AAAAACAATGATACTTTCATCAACTACCTATACACCCTGCGGGTCA ATTATTTTTTTTTCGAATAACCGCTGAGGTTGGAAATATAGAAACA TATTCCAGATCTGTATTTTCAGTTGCTAGAAAAAGGTTAATATAAT CATTAAGGTTTTCAGCATATAACAGGTATAATTGATATATAAGCAT CGTAATTTTCATTCAAAATGGAGAGCTACTGCTTCTGATAGATTGT ACAATCTCAAGAAATCAAGAACAACAACCATACCATGAGT >YMR175W Chr 13 (SEQ ID NO: 2) TTGTGTTTAGACTTAAGTATGAAAATTTTATGTATGAGCTGTGGCT ATGTATCCGCTGGCAAATAGGTCTGCTTTTTCTACACTTTCCACCC TCAACCTAACAGAGCCCGCTGGCACAAATAATCGATAGTAGGACAA CAGAGCTACTCCTTCTTATGCCCCGCCCCTTTGAGCTTGTTGTATT GCTCTTGATAGTTGTGTTTTTCACTTTCATCAGCATCGGTAGTCTT GCCGTCCTTGTCTTGACTAGCCATTTTCTTAAAAGCGTCACTCACT ACCTTTGCATCGCCCTGCAATTTTTCCTTTGAGCTCTGAAATATTT CGCTCACTTTTTGTTGGTCTGTATTCATTCTGGATGTCTTGGTTGT AGAAATTTCTTTTATTGGTTCATTAAAGTCAAGGTAAATGGCGAGA ACTAGAATAGAGTTTTATTCTTTTTACCGTTATATAGATAATTCTA GCCGGGGGCGGTCGCCCCTGAGATTCCCGACATCAGTAAGACATAG TACTGTACGATTACTGTACGATTAATCTATCCACTTCAGATGTTCA ACAATTCCTTTTGGCATTACGTATTAATACTTCATAGGATCGGCAC CCTCCCTTAAGCCTCCCCTAAATGCTTTCGGTACCCCTTTAAGACA ACTATCTCTTAACCTTCTGTATTTACTTGCATGTTACGTTGAGTCT CATTGGAGGTTTGCATCATATGTTTAGGTTTTTTTGGAAACGTGGA CGGCTCATAGTGATTGGTAAATGGGAGTTACGAATAAACGTATCTT AAAGGGAGCGGTATGTAAAATGGATAGATGATCATGAATACAGTAC GAGGTGTAAAGAATGATGGGACTGAGAGGGCAATTATCATCCCTCA GAATCAACATCACAAACATATATAAAGCTCCCAATTCTGCCCCAAA GTTTTGTCCCTAGGCATTTTTAATCTTTGTATCTGTGCTCTTTACT TTAGTAGAAAGGTATATAAAAAAGTATAGTCAAGATG >YFRO26C Chr 6 reverse complement (SEQ ID NO: 3) GAGGTTTCAACATGCCAACAATGGAAGTGGTTAAGAGACGTTTTCT GGTTTCTGGGCAGCTGTTACATAGAATCTCTGATTTACATGCTCAA GTATTCGCAAAGATCGGTATGATGGGAAAATAGGTGAATTTTGGGA TAATGACTGAGATTATACCGTTGTTAATGCTATAATATTAATTATA CAGAATATATTAGAAGTTCTCCTCGAGGATATGGGAACCCACAGAA GCGAATCGATGTTTCTACATAAAAGAAAAAAATAATCTCATTTTAT CTTCGGTTTTGAATCTTTTCATTTTTTTTTCCTATTACATTATCAA TTCTGGCATTTCAGTGTTTATAAAAAGATCAAATTGCTGTTTGAAA CTCATTGCGCTAATTCCATAATTTTGCACCATGTATGCTCATGACT CCATATAGGACAACATACTGGTAGGAATATTATCAAGTGAACGATA ACGGTTCTTCTCCCAACAAGAAGTAAGCCTGGTGAGTGTATTTTGA AGCTTTTTGGAGGGGCGGCCACGGAATAAGATATGAACACATACTG GCAATTGGGCTGAGATCTGATTACATTGTCGACAGATTCCCATGAA GGTGTTTGAGAGAATTTTGATTGAGTCGTTATACAAATTGCTGTGG ACACGTACGCATAAAGTAGTTCGGGCAGCTATGTTTGCCACGTAGT AGCTACAATATTAAGCATAGCAGACTAAATGCAATTGGCTGTGTTG AAAGAAACTTCTGAACTGAGATTCAAGTAACGTGATTGTGTGCGCC ATTTTACACAGGCTGCGCGGCAAATCAAAACCAAAGATACTTCTCC GGAGGTATACGTGTTGCATTTTCAACAGACTATACGAGTTTTTTCT GATCGTTGTATATTTAAGTGCAGCTTGGACTTACAAGCTCTATACT AGGATAATGATCTCATTGGATTCAAGAGAAAGAAACTCTATACTGG CGCCAAATTAGCAGTGTCAAATTTCGAAAAGGTGATG >YJL153C Chr 10 reverse complement (SEQ ID NO: 4) TTCTTTTTTTTTTTTTTTTTTTCTTTTTGGGAACGGGGGAAAAGGT CTCACTAGTATATAAAGGAAAGAGAGTACAGCACGAATGAGCCAGC TGCAGGAAAGGGGCTAGGTTAAAAAATAAAAACCCAGCAGAAAGCA AACAACCAAATATAATTTAGAAATGGACAGAGACCATATTAATGAC CATGACCATCGAATGAGCTATTCCATCAACAAGGACGACTTGTTGT TAATGGTTTTGGCGGTTTTCATTCCCCCAGTGGCCGTCTGGAAGCG TAAGGGTATGTTCAACAGGGATACACTATTGAACTTACTTCTCTTC CTACTGTTATTCTTCCCAGCAATCATTCACGCTTGCTACGTTGTAT ATGAAACGAGTAGTGAACGTTCGTACGATCTTTCACGCAGACATGC GACTGCGCCCGCCGTAGACCGTGACCTGGAAGCTCACCCTGCAGAG GAATCTCAAGCACAGCCTCCAGCATATGATGAAGACGATGAGGCCG GTGCCGATGTGCCCTTGATGGACAACAAACAACAGCTCTCTTCCGG CCGTACTTAGTGATCGGAACGAGCTCTTTATCACCGTAGTTCTAAA TAACACATAGAGTAAATTATTGCCTTTTTCTTCGTTCCTTTTGTTC TTCACGTCCTTTTTATGAAATACGTGCCGGTGTTCCGGGGTTGGAT GCGGAATCGAAAGTGTTGAATGTGAAATATGCGGAGGCCAAGTATG CGCTTCGGCGGCTAAATGCGGCATGTGAAAAGTATTGTCTATTTTA TCTTCATCCTTCTTTCCCAGAATATTGAACTTATTTAATTCACATG GAGCAGAGAAAGCGCACCTCTGCGTTGGCGGCAATGTTAATTTGAG ACGTATATAAATTGGAGCTTTCGTCACCTTTTTTTGGCTTGTTCTG TTGTCGGGTTCCTAATGTTAGTTTTATCCTTGATTTATTCTGTTTC ATTCCCTTTTTTTTCCAGTGAAAAAGAAGTAACAATG >YPL033C Chr 16 reverse complement (SEQ ID NO: 5) GAAGTTACAAATAATAACAACAAAGTTAATAACAGTAGTAGCAACC CTGATATTTCCACCAACTCGGTAGTTCATAACGCAATGCAATTTAC AAATACAAACAACAATACAAGTAGCACTGTGGATATAAACGATCCC AAAAATATTGCACCCCCTCCTACAACCTCTGTTTCAGCCCCAAGCA CTCCAACCTTGTCCTCATCAAGTCAAATGGCGAATATGGCTTCGCC TAGTACCGATAATGGTGACAATGAGGAGAAAAATGGTGGTAAGAAG AAGAGATTTGGCCTATTCAAAAAAAAAAATAAATCAAAGAAATAAT ATCCTTCGACAGCTTAATGAACACGCATGTAAATGTTTTGTAAACA GTTTGTTTTTTCGTTTTTGTATCTGTTAATTTTCTATTATTTATTT TTTTAGTTTTTTTTTGCGGTAGAATTGGGTTATCACTGAATCTATT TTATTTTTTGGGTTGGTTTCTCCCTGTTTTCAGTTTGTTTGAATTG GTGTTTAACAAAATCTGGAATTATTCACTATAATTATTTCCTCTTT TTAGTTTGACCAAATAAACTCAACTATCTTGTGTTATTTCTTTGTA TTATAGCTTTACACATATTTAACTATCCATACCTTTTACTTTTTGT ATATACTGTTAATTTCATAAAACACGTTTTAGTACCAGAAAATCGT GTCATAGCACCGTTTTAGCAGTGATTTTTAAAATTGTCCAAGGTGC CAATAAATACTGGTGGGAACAACATTTTAATTAGAATAGCTAAAAC CTTCTAAGAAAACTATCCCAGCGTAGAAAGAAAGAAATCTCTATCA GCCGCGCAAGTGCAGTATCTCTTATTTTTGCACGGCCCCGTCGCTA TATTGTCACACGCATTTGAATTAGTGACTCAATAATAATACAGATT TGTGACGTATAAAGAAACCACAGAAAAACTGCGTATGTCCGAAGCA CAGGTCCACTAGTAATAGAGCCCAAAAATCTGACATG >YOL058W Chr 15 (SEQ ID NO: 6) AGGTTGCCACATACATGGCCAAGACCGGTAAGTCAGCCTTGGAAGC AGAAAAGGAATTGCTTAACGGTCAATCCGCCCAAGGGATAATCACA TGCAGAGAAGTTCACGAGTGGCTACAAACATGTGAGTTGACCCAAG AATTCCCATTATTCGAGGCAGTCTACCAGATAGTCTACAACAACGT CCGCATGGAAGACCTACCGGAGATGATTGAAGAGCTAGACATCGAT GACGAATAGACACTCTCCCCCCCCCTCCCCCTCTGATCTTTCCTGT TGCCTCTTTTTCCCCCAACCAATTTATCATTATACACAAGTTCTAC AACTACTACTAGTAACATTACTACAGTTATTATAATTTTCTATTCT CTTTTTCTTTAAGAATCTATCATTAACGTTAATTTCTATATATACA TAACTACCATTATACACGCTATTATCGTTTACATATCACATCACCG TTAATGAAAGATACGACACCCTGTACACTAACACAATTAAATAATC GCCATAACCTTTTCTGTTATCTATAGCCCTTAAAGCTGTTTCTTCG AGCTTTTTCACTGCAGTAATTCTCCACATGGGCCCAGCCACTGAGA TAAGAGCGCTATGTTAGTCACTACTGACGGCTCTCCAGTCATTTAT GTGATTTTTTAGTGACTCATGTCGCATTTGGCCCGTTTTTTTCCGC TGTCGCAACCTATTTCCATTAACGGTGCCGTATGGAAGAGTCATTT AAAGGCAGGAGAGAGAGATTACTCATCTTCATTGGATCAGATTGAT GACTGCGTACGGCAGATAGTGTAATCTGAGCAGTTGCGAGACCCAG ACTGGCACTGTCTCAATAGTATATTAATGGGCATACATTCGTACTC CCTTGTTCTTGCCCACAGTTCTCTCTCTCTTTACTTCTTGTATCTT GTCTCCCCATTGTGCAGCGATAAGGAACATTGTTCTAATATACACG GATACAAAAGAAATACACATAATTGCATAAAATAATG >YOR255W Chr 15 (SEQ ID NO: 7) CTTAGTATACGATTGTGTTCTTGCCCACCATCTACTAACAAAATAT GGCAAGATTAAACCTAGTAGCGCAACATAACAAACCACTAATAATG GAGATGCACTTCCATCTACCAAAAATCTTGGTAGAGCGATACCATG TGAAGTAGATTGTGGGCCATCTGGATGACCGTATTTCAAATAGTTT TGCCTAACCAATTCGTCAGTAAGGGATTCGTAAGCCTTCGTAATCT GAACATAAGTTTCTTCCATCACACTTTTCTCATCAGGTGTTAGGCC CTTTGCTAATTTATCTGGATGAAATTTAACAGATAATTTTCTATAA GCAGATTTGATGTCTCTATCGGAAGCACTAGTAGAGATACCAAGGA TTTCATAAGGATCAAATAATTTTGTAGCAGCGTCTTTAATCGCGTC ATTACTATTAATCCTTTGCAGAAGAATTGCAACTAAGATCCAACCC ACAATAATTATAATATTTCTCCTGCTCCATATTTTGGACTTCTTAT TACTATTTTTATCAAACTTCCTTCTAAATTGTTTGATTTCATCACT GGTGTATTCTTCATTCAAGTTCTTGAAAACTTCCTCATTAAACTCC TTACTCTTCCCTGAATTCCCATCTTCAGCATTGGCCCCAAAAAAAA TTTGGTATATTTGAAGCAGTGTCATAGGCCCGACGACCATCAAGAG CCCCGTTAAAATGAAGGACGGCCACGTCTCACTAGCCTCATCATAC TCGTAATTTGTAGGCATTGTGCTGTAATATGCAGTATATTTATTTT GTTGCGAAGGCCTTCTTTGGTCAATTATAACTGACTATTGTTCCAG TCGCATCTTTTATTCGTTCAGTGATCTTCGACGTGTTCAAGACAAA TTTTTCAGAAAACGCCTTTCCGTAACGAGTGACCAATTCGCGTTAT AAGAGCGATTGTGTCAGTAATGAAGTCAGATTGTGACATTATAAAG CTAAGACGTTAATAACTCAAAATAGAAAAGAAGCATG >YDR250C Chr 4 reverse complement (SEQ ID NO: 8) AAATAAGAGGTTTGGCCAAAACGTGGTCATCCAAGGTTGATGGATT CTTCTCTTCTAATATTATTAATAATGGATCGAAACATATTTGAGGC AAAGCTAGTTCCCATTCTTTTGCCAAGAAAGCGGAGGGAGAATGAT CGTAAAGAGTCACAACGTCCCTAGGAAACAGTTTTTGGAACAATTT CTGAAATGTATTCAAAATAGGAATAATATCACTTGAATAGCTGTTT TCGTGAACGGATGTCGTTTGACCGATCGAAACAGAAAAGGATTTGG CATTTGCAGTCGTGAACTGTTTGTATGAGCCATTGTCCAACCGTCT TATGTCATAATCGGTGAAAATGCTGAAAATATTTGACAGCGAAAGA TCAACTGAAGCCTTGATGAATGGCTCCAAATATATAAACCCGCTAC TTTCAAATAGTATCTTTGTTGTCTTATTCATCATAGGTTTTATATC TCTCAATACCTGCGGGATTTCTTGCAGTGAAGACGCACTCATTATT ATCAAGTCGAATACCAAGCCACCATTTTCATTATTAAGGTCTACTA AATCTAGGAGCGATTGGAAATGGTTTTGAATCTGAAACCGTTCCGT CCCATAAAATAGTGAACTAACCTCGTAGTTGGCATTTTTTGAGTTG TTCACAAGATAAAATTCTATATTTTTGGCATGTTGAAACCTGGATG TGTACAGAATGAGATTTGGGTGATCTCCGCATACCAAAACCCTTAA TGCAGATGTCATTATTCAATATACCTATCGCGAGATATGCCGGGAA TAAAATGTAGGAAACAAAAAGAAAAATATATGCACAGTAGTTCAAA CAGAATAGAAATGACGGAGAGCAAATATTTGGGTAGAATCACAGAC TTTAGTGTTGGTTACAAGCTTTTCGAATGGATGTAGTTTGTAATCA AAGGACACTAATAATAGCGAAAAAAAAAAGGGCAAGTATGTTGGCA GTCGCCTCTTTTTCAATTTAGCGGTAAGTTTTTAATG >YDR446W Chr 4 (SEQ ID NO: 9) CGCAAATGATGAGAAATAGTCATCTAAATTAGTGGAAGCTGAAACG CAAGGATTGATAATGTAATAGGATCAATGAATATTAACATATAAAA CGATGATAATAATATTTATAGAATTGTGTAGAATTGCAGATTCCCT TTTATGGATTCCTAAATCCTCGAGGAGAACTTCTAGTATATCTACA TACCTAATATTATAGCCTTAATCACAATGGAATCCCAACAATTACA TCAAAATCCACATTCTCTACATTACTAGTATATTATCATATGCGGT TTAAGAAAATGGTATAAAGATTAAGAAACAGTCATGAAAATTTAGT GAAGCTGAAATGCCAGTATTGATAATACGATAGAATAATGAATGAC AAAGTATATAAGGAAGATGAAGTAACATTATTATGGAGAACTATCG ACTCCCTTTTGTGAATTTCTATATCCTCAAGGAGAATTGCTTGTAT ACTATGTATATATAATATTATAACCCTTGACAACAATGGAATAATT AGTCCTTAAACGTTAGACTGGCTGGGACAGCACGACCTCTGTTGGC TAATTTTACTTTTCCCACAACCGTAGATCTTGATTTCATGACTGTT TTCGTGGTAATGTCCGAATGATACATATATAAGTTATATGCTTTCA CTTTATAAGTATTAGCGTTTTTACTCACCATCCACTGCTTTGAGAA GATGTGGTCAGCAACCACGCAATACATCACATATTTTGGCACGGGT GATGTACCGATCTAATGGCTAAGCTTCCTTTTGGAAGCTGATAGAG ATCCAGATTTGCATCTCTATCGCTATTGTCGTCATCGACACTGCTC ACTTAGTGCTGCAGGTAAATTCCGTTTTTTTCCAAATTAATATTTA TGAACGTTATGATGTCAAGTTTTTTCAAGAAGTAATTATCCGCGAA AAAAAGAATATAAAAAATACAAATGTGCATAGATCCTCACATAGTA TACAACTAAAAAGCAAACAAAAGAACATCCTCAAATG >YDR536W Chr 4 (SEQ ID NO: 10) CAATGATTCTGAAATACTCCTTTTACAACCTTTGCAAAGATAATGT CTTTCAGTCTGATATTACGAGCGACCTAGAACCACTAATCCATATT CTTCATTCAACTTACTCCATTTTCCTTGGCAAACAATGCCCCACAA TCATATACGTCATAACTATAAGGGATATGTCTGGAATGCGGCCAAG ATAGAATTAAAGGGCTGCAGAACACCACTACTGATACTCATTGCCA AGGCTAGGAGGCACCATCCGTTTCATTTTCTTTGAGGTAAGCCAAT CATGAAATAGTATACACATCCATAACGGACGTACGGACGAAATAAG TGCCGTTGTCCCACTATTCCACCGCATTTGGCCCATTTGGCTCACT TTGACTCAACTTGCGTCATTTTAACTGATATGAAGGGTCCGACTTT GTCCTTTTTCGGCCACCGCATACCCCACGGCGATGCCTCCGCTACC TGCATTTGAGTAGCATCTCCGTTTCGCGGGGTATTCGGCGCTACGT CGCCTGTTCGAGCGGCTCTGTTCGTTGCATGAAACTAAAATAAGCG GAAAGTGTCCAGCCATCCACTACGTCAGAAAGAAATAATGGTTGTA CACTGTTTCTCGGCTATATACCGTTTTTGGTTGGTTAATCCTCGCC AGGTGCAGCTATTGCGCTTGGCTGCTTCGCGATAGTAGTAATCTGA GAAAGTGCAGATCCCGGTAAGGGAAACACTTTTGGTTCACCTTTGA TAGGGCTTTCATTGGGGCATTCGTAACAAAAAGGAAGTAGATAGAG AAATTGAGAAAGCTTAAGTGAGATGTTTTAGCTTCAATTTTGTCCC CTTCAACGCTGCTTGGCCTTAGAGGGTCAGAATTGCAGTTCAGGAG TAGTCACACTCATAGTATATAAACAAGCCCTTTATTGATTTTGAAT AATTATTTTGTATACGTGTTCTAGCATACAAGTTAGAATAAATAAA AAATAGAAAAATAGAACATAGAAAGTTTTAGACCATG

>YOR255W Chr 15 (SEQ ID NO: 11) CTTAGTATACGATTGTGTTCTTGCCCACCATCTACTAACAAAATAT GGCAAGATTAAACCTAGTAGCGCAACATAACAAACCACTAATAATG GAGATGCACTTCCATCTACCAAAAATCTTGGTAGAGCGATACCATG TGAAGTAGATTGTGGGCCATCTGGATGACCGTATTTCAAATAGTTT TGCCTAACCAATTCGTCAGTAAGGGATTCGTAAGCCTTCGTAATCT GAACATAAGTTTCTTCCATCACACTTTTCTCATCAGGTGTTAGGCC CTTTGCTAATTTATCTGGATGAAATTTAACAGATAATTTTCTATAA GCAGATTTGATGTCTCTATCGGAAGCACTAGTAGAGATACCAAGGA TTTCATAAGGATCAAATAATTTTGTAGCAGCGTCTTTAATCGCGTC ATTACTATTAATCCTTTGCAGAAGAATTGCAACTAAGATCCAACCC ACAATAATTATAATATTTCTCCTGCTCCATATTTTGGACTTCTTAT TACTATTTTTATCAAACTTCCTTCTAAATTGTTTGATTTCATCACT GGTGTATTCTTCATTCAAGTTCTTGAAAACTTCCTCATTAAACTCC TTACTCTTCCCTGAATTCCCATCTTCAGCATTGGCCCCAAAAAAAA TTTGGTATATTTGAAGCAGTGTCATAGGCCCGACGACCATCAAGAG CCCCGTTAAAATGAAGGACGGCCACGTCTCACTAGCCTCATCATAC TCGTAATTTGTAGGCATTGTGCTGTAATATGCAGTATATTTATTTT GTTGCGAAGGCCTTCTTTGGTCAATTATAACTGACTATTGTTCCAG TCGCATCTTTTATTCGTTCAGTGATCTTCGACGTGTTCAAGACAAA TTTTTCAGAAAACGCCTTTCCGTAACGAGTGACCAATTCGCGTTAT AAGAGCGATTGTGTCAGTAATGAAGTCAGATTGTGACATTATAAAG CTAAGACGTTAATAACTCAAAATAGAAAAGAAGCATG >YDL243C Chr 4 reverse complement (SEQ ID NO: 12) CATAAGAAACAAATTTTGTAAGTTTCTTGTGCCTTTTGAGTTTGAA ATCATTGACCAGAACAATGAGAACTCTAAACACGACAAATGGATCT TAAATCAATTTTCTTGAAAACATCTTCCAGTTTCGATATTCGCACA TTTGCCGGTAAAATAGTGCAATCTGCCTATACCTTTAAAATGGGAT CTTGAACGCGTACCTGAAGGTTTTTTTAAATAAGGCCGAACCTAAA TGTTGCCTTCAAAATTAACCTGTATCAAATTTTGAAGCCGAAGTTG GTATCCTCACATTGTCTAACCTCATGGTCTCCTAAAGTCCGGCGAT CACTTTCCGTTGCGTGACTATTGATGATCAGACTGTCAACAATGTC GTTCCGGGCCTCCATAGCTTGAAGAATTTTCGTTGACGGAACTAGA GGAATGGCAGATGGAGATGACCTTAGTTTCATGTCGCCTTGATAGT TATCAAAGAGTACAGAAACAAGACGTCTCTTGCTCAATAATAAGGA TTGGATCAGGTGCTTACAAATTTTATTCGTCATACAAACAATTACT AATATTTTTTTAATATTAAGCGTACCCCTATTTGATTGGCTCTCTT CTAAATTCATACGTTTTAAAATCCGCTTTCAACCGTCAACATAAAA TTAGTAAGCAGACCTCGTTCCAAGACCCAACTAAGTTGCACTAAAT ATCCTCGAACAAATTGGGGGCAGATTTTTGAACCATATAAAAGTCA TGACAATATTTCCAGATCAAGGACAGTTGCAGTTCTTCCTTTCATC GGCCAGCTGACGAATTGACTGAGCGGCTTTGTATTTCACTAGAATA CACTTCCTATAGCTACAAAATATTATTCAATAATATTAGTGAATTA TTTAAACCTCTACCTGAACCACCTACCGAGTTGGGACGTCTCAGGG TTCTTTCTAAAACTGCCGGCATAAGAGTTTCACCGCTAATTCTGGG AGGAGCTTCAATCGGCGATGCATGGTCAGGCTTTATG >YDR256C Chr 4 reverse complement (SEQ ID NO: 13) AGAACATCCAAATTCGGAACTACTAAGAAGATATGGGTATGTTGAA TGGGACGGTTCGAAGTATGATTTTGGAGAAGTGTTACTTGAAAATA TTGTCGAGGCGTTAAAAGAGACTTTTGAGACGAATACTGAATTTTT GGACAGGTGTATTGATATCTTACGCAATAACGCCAATATTCAAGAA TTCTTAGAAGGTGAAGAAATAGTACTAGATTCATATGATTGTTATA ATAATGGTGAATTGTTGCCTCAACTAATACTTTTGGTCCAAATCTT GACAATTCTTTGCCAAATTCCAGGTTTATGCAAACTGGACATAAAA GCAATGGAAAGGCAAGTGGAGAGAATTGTAAAGAAGTGTTTACAAT TGATAGAAGGTGCCCGCGCCACTACAAACTGTAGTGCCACATGGAA ACGTTGTATTATGAAGCGTCTAGCCGATTACCCCATAAAAAAGTGC GTTTCTATCGAAAAACCTTCGAAAGGAAACTCATTAACAAGGGAAG AACTAAGAGATGTTATGGCTCGGAGAGTTTTGAAAAGCGAAATAGA TTCGCTGCAAGTTTGTGAAGAAACCATCGACAAGAATTACAAGGTT ATTCCTGATGAAAAGCTGCTAACTAATATTTTAAAGAGAAAGTTGA CAGAGGAAGAAAAAAGCTCTGTCAAACGTCCTTGCGTGAAGAAGTG AGCGGTTGTTCTAACCACTATTTAAAGCCGCAATTAGTAATGCAAA AAGTTGGCCGGAATTAGCCGCGCAAGTTGGTGGGGTCCCTTAATCC GAAAAAGGACGGCTTTAACAAATATAAACTCCGAAAATCCCCACAG TGACAGAATTGGAGAAACAACCAGTTTTGATATCGCCATACATATA AAGAGATGTAGAAAGCATTCTTCACTGTAATGTCCAAATCGTACAT TTGAATTTCTTGTAGGTTTATTTAAAAGGTAAGTTAAATAAATATA ATAGTACTTACAAATAAATTTGGAACCCTAGAAGATG >YFL020C Chr 6 reverse complement (SEQ ID NO: 14) GTTGAACTTTATTCAAATATCATCGAAGTAAGAAGATATACTACTA AAGACTCCCTTTGCTCTATATTCGAGTCAGGCTCCACCAGTCATTT CGAAATTAACCAGTTACAGGTCAAAAGACTAAACTTACTGCAAAAC CAATTTGCTTCTGTTTTCACTTCTTTCCACCCCAAAGATAATACAA AGGGCATACATATCAATTTTTTTTCACCTGTCACTAGGATAACTGA CCTTCAATATTCCTTTTTTTATACGAATCAGATACTGTTCGGTACA CGATATCTAATTAAAATGATTCAAAACTTTGTAACAGGTAAAGTTT TCACTAGAACCAATCAATCCAAGTGAATTAGGGGAAACCATAGTTG TTGATTTGTAGAAACCTCACATTGTACATTGTTGGTTTGTTGGGCA TATCAGAACGAGAGATTTTCCAACATTCAATATACACTAAACCCTA TGACGAGTCCCACAGATGGCGTAAGGTTTTTATGATTTCAGCAGGG TACGACGACTAGTACCATATTAACATTTTTTAGTGTTTCTAATTTG GGAAAAGGTCCGTGTTTTTTCTCCTAGCAACCGTTTAGTGCCAAGG GTTAGGCAATTGAACGAGGCCAAGACAATATTGGCTTTGCTTCTAT TACTTGGCTAACATTGTGTCTGCAGGTCGAAAGGCACCTTTACTGT AAGGAACATTCTTGCGCTCTAAACATACGAAGATATGGGGAATATG AAGCGTGTTTCTTATACGAAGTGCAGCATCGTTCAAGGAAAATACA CCCCCATAGTAATAATGGCTAAGTGGCCAGGAATTAGAATATGTGA GATATGAGTGCAAAATGAGTGACCAGTAATAGCCTGTTTGGGATGT AATTGCTCAAAAAATTTATATAAATACAGCGGTTTGATCAGCTTTG TTTGAGACATTTCTCTGTTCTTTTCCTTCCAGTTAAGCTTATATCT CCACTAAGCAACAACCCAAAAAACAACAAATACAATG >YPL205C Chr 16 reverse complement (SEQ ID NO: 15) CAGACTTGTTGTCTGTGCTGTTACTTGCACTTGCTGCATTGCTATT TGCGTTCAAATCACCTTTTTCGATGAGGAGGTCCCTTTGCTTCTCC ACCATCGCCTTTGTGTAACGCAACATTGTCCAATCGAACAAGTGGT CGTTGTGATACTCTAGTTTAATACTCAGATCTTTAAACAGCCTTGC CAAGAACAAATAATCTGGCTTCTCATCGAATTTCAAATTCTTACAG TAAGCCATATATTCTTGAAACTCTAATGGTAAACCTGAACATAGAG TTTCCACGCTAACGTTTAATTTCTTTTCCATGATACGATCATACTT TTGTTTCTTGGTGGTTGCTTTCAAACCCTGCCATGGCAAAGAACCC TTACAAAAATAGATCAAGACATAACCTAGTGATTCTAAGTCATCTC TTCTACTTTGCTCTATTCCAAGATGCGTATTGACACTTGCATAACG AGCTGTACCTGTCAAGGACTTGTTCTCCCTGTAAGGAATATGACGA TGTGTGTTGAAATCTCGGTATTTCTTTGATAGACCGAAATCAATAA CATGAACGGTGCTACCACGGCGTCCTACCCCCATTAAAAAGTTGTC TGGTTTGATATCTCTATGAATGAACGACCTTCCATGTATATACTGA ATACGGCAAAACATTTGCAAAGCCAGCATGATAACCGTCTTAAAGG AGAACCTTCTGTGACAGTAGTTGAATAAATCTTCCAAAGATGGGCC TAGAAGATCGATGACCATAGCATTATATTCACCCTCTCTGCCAAAC CATCTGATGAACGGGATTCCCACACCACCGCTTAAGTATCTGTAGA CGCGGGACTCATAGTCCAATTGAGGATGTCTGGACCTGATCGATTC CAGCTTGATGGCTACTTCTTCACCACTAATTAAGTTCGTGCCGTGG TAAATGTCACCAAAGGAACCACTCCCAATCTTCCTGCCAATACGAA ATTTCCTTCCTACTCTTAAGTCCATCTCTTTTTAATG >YGL205W Chr 7 (SEQ ID NO: 16) TCACTCAACCACCTCCAAAAAATAACAGGTTCATCTAAAGTAAAAG ACTTTAACTTGCTCTTAGTTTCCAAATTAAATATCTGCACGATAGT ACCATTTGCTCTAACGGAAATAACCATCTGAGATGGATGCATGATA GCAGAATCACCGCCCATATTCTTCCTTGTCACTTCATTGCCTTTGG CCAAATCCACGATTGCAACAGAGTTTGTACCGTCCTTTGTTTCTCT AACAGTGACGAAGTGGTCACTCTCGAAAGTAGTTGATCTGAAGTCA AGGAATTGAGGGGAAATTCCTAAGGACATCAGATCGACCAATTCGG TAAATTCAATGGGTAGGTCACTCATTGGTTAGAACTTTCGTGATAA TTTATTTTTATAGTTGAATATCTTCTTTCTCTCTCAACTCTGATCC GGATTGTCGAGGTTTCAATAAGTTACTCTGAACAACTAATCAAAAT ATCTCCTTATTTCTGTAGATTCCTTCAGTTCCACTTTTTACTTTTC TTAATTCTCTTTGTATTTATTCCTAGCGACGAAAAATGCGAGATCT CGACCAAAAAAAGGGGGTAGGGTAATAAAATTAACCCTATTATTTT TTAACTTTAAAACCTATAATGTGCTAATATTTTATTATAAACCTCC TTTTTTTGCGTTCAAACCCTGACACATTTTAAGCCCTATATTTACG GTATTAGTTGATTAAACTCCGAAGCGAAAGGAATTCGGTCATTAGC GGCTAATAGCCGTTGGGGTAAATCACCTACAAGCAAGTACACAAGA GAACGTTGGCGTTGTTAAGTCAAAGCACTAATACATTGGGGCTTTA AGAGTGTTTATAAAGGTCTAACCTGTAAAAATTATTTAAACAACTT GAACAGGCCTTAAAGTTTTCCTCATTCCGCTCATCATCACTAATAT TGCTCTCCGTTTTTGAATACACACTTGACACTAATAAGTATCACAG AAAAAAAGAAAATATAATAAATTAGTATTGCGATATG >YGL117W Chr 7 (SEQ ID NO: 17) AAAACGGCTCCTAGTTATCGTCAGTTTTGATAATTAGTAACTAGAA TATAGTATCACCAAGAACAGGCCAGGTAATATACTAGAAGTTGTGT ATAACTACTAATATTTTTATACATATAGATGCCAAGTCAAGGTCCA ATTAGTAGATTTTTCACTCTACCTTGCATTATTACCTGAAAGATCG TTTGTGTTTCCTTAAATTCGCCAGAGGTGCAAACGAATGTAAATAT CTACATCAATTTACGGTTTCACGCCCGTTTCGTTTCTAATGGCAAC TCATGTAAACTGTGATAAACCCGTTATTTCAGTTTTATTTTCTGCT AGTATAAAGGATGATAGTAGCCATTTCGCTGGAATATGTATCGGGT TTAAAAGATGGCATAGTTCGAAACATTTTCGCACAAGATTCTAACT GTCTTCGAACGTCGTAGAAACCGCAACGCAAGAAATGACAGCGCAA TAAAATTTATTTTACTAACTGATAGAACAAATGTAAAAAATTTCAT AATATCAAGTAGAATTCTTTATTCTCTTTGTGAATTCCTAAACCCA TGAAAGGGACTTGTAGTATAAGCTGGATACCTATTTTCATTGGCTT CGTTTCCAAATGACACAAAACCATCACAAAAGGAAATAGTCCTTCC ATAGTTACCCAATCATTCTGTTGCATATTAAATGAACAGCTCCTTG TTGATAATGCCAGTGTGGCATATTCACCGCTGCAGTTATTTCTTTT CATATATAATGAGTCATTTGTTTCTGTCATCACTTTTCTATACTTT CTCTTCCCCGCGTGTTTTCCGTACACCAACAATATATGCCATAATA CACGTAACATTTTTTTATAAAAAGAAAAGGTAAGTGATATATATAA AATAGCGCCATGAGTAGGAAACTTTTCTGTTACTGCAGATATGTGC CAGACTGGCTCAGGTGGCATAAACACAGATTAATAGTATTGGCGTT GCTGAAATAAGAAGATCTGTAACAATATCTTACAATG >YHR029C Chr 8 reverse complement (SEQ ID NO: 18) TCTAAAAATGTTCAGGACTACATACATCAATTAGGTTTCATTCCAA AAGTACCTTTTGTCAATTTATACCCAAATGCCAATTCACAAGCATT AGACTTATTGGAGCAAATGCTCGCGTTTGACCCTCAAAAGAGAATT ACCGTGGATGAGGCCCTGGAGCATCCTTACTTGTCTATATGGCATG ATCCAGCTGACGAACCTGTGTGTAGTGAAAAATTCGAATTTAGTTT TGAATCGGTTAATGATATGGAGGACTTAAAACAAATGGTTATACAA GAAGTGCAAGATTTCAGGCTGTTTGTGAGACAACCGCTATTAGAAG AGCAAAGGCAATTACAATTACAGCAGCAGCAACAGCAGCAGCAACA GCAACAGCAACAGCAACAGCAGCCTTCAGATGTGGATAATGGCAAC GCCGCAGCGAGTGAAGAAAATTATCCAAAACAGATGGCCACGTCTA ATTCTGTTGCGCCACAACAAGAATCATTTGGTATTCACTCCCAAAA TTTGCCAAGGCATGATGCAGATTTCCCACCTCGACCTCAAGAGAGT ATGATGGAGATGAGACCTGCCACTGGAAATACCGCAGATATTCCGC CTCAGAATGATAACGGCACGCTTCTAGACCTTGAAAAAGAGCTGGA GTTTGGATTAGATAGAAAATATTTTTAGGACAAAAAACTATAAGTA ACCGGGGAAGTATAGAATCACCATAGATGTAAGCTTACAGACAATG TGTATATATGATGTATATGAACGTATACAAATATATATATATATAC GTGCTCTTGTTGTAGCTCGTATATCAAATTCCTCCTCCGACGCTTA TCTTAATCGTACTCCGCGGAAGTTTGTTATCGCCTCTTGAATTCTT TCTTTTCGTTCATTTATGATTAGTCATCTATAGACAATATTCATTA TTTAAGCACCTAGAATACTAAACTAAATGTCTAAATATGACACAAG GAAGATAAGATAAAAAAAACCAAGCGCTTAGAATATG >YML116W Chr 13 (SEQ ID NO: 19) CATCGGGATCTTCCGACTCGTCATCAGACGTCGAGGTCATTATGCA CTCCCCGAGCGATCCTGAATACGCTTTAAAATCACAAACTCTAAGA AGCTCGAGTCAGACCGTCATTAATAGTAAGAGACCAGTAAAGATAG AAGACGAGGAAGAAGCCGTAGGAATGTCACAGCTCAATTATAGGTC GTCATTAAGACAAGCTCCTCCAAGAGCTCCCTCAACTTTGTCATAT AATCACTCGAAGAACAACGAAACGCCAATGCAAGATATTTTCACAA ATGGCGAAACAGCAAATAACAGAAAGAAGAAGAGAGGATCTTTTGC AAGGCATAGAACGATACCAGGATCTGACGTCATGGCCCAATACCTT GCACAAGTGCAACATTCGACATTTATGTATGCAGCCAATATTTTGG GCGCCTCTGCGGAAGACAACACGCATCCTGACGAGTAGTATAGCTG TGCTGAGCCTGAAGTATAATGCATATCCATCGGACTATTTAGACAA AGCCCAAGGAAGCCTAAGGCGGCCTGCCAAGGTGTTTCTCCCTTTT TTTCTCCGATTTCTTTGTATAAACTAAATAATATAGTGATTACTAA TGGAATGGCGGTATTATGCACCTAACCTGTTCATTCTGCCACAGAT TACGTAAGCGATTTATTGCCGGCACTTGTTGTCTTAATGACCGAGT CACCAATGTGGAACGATAATTTTCTCTGACTCAAACCTGTTAATTT TTTTCTACTTCGTTTCGTTAGCGACGACGTCAAGCCGCAGGATCCT GTCTGCCTTGACCTCTTCTCTACCTTCAGAACTTACACTTTTCAGG TAAGATGACCTTTATATAAAAGTTGACACTATTACAGTTGTTTATA AACGTCTGAAGAATGAGACGTTTTTATAAAATGAATAAAATGCATA TTCTAAGTTTAAAACAACATTTTCAAAGTGTACGATTGTAAAAAGA GAGGCAATTAGAGAATCTCAAACAGGTAATAATAATG >YJR109C Chr 10 reverse complement (SEQ ID NO: 20) GAAATCCAATGAGAATACCGCATAATCTTTCCCAATTACCTTGATA TTTACAAAAGACCATAGATCCTTACCCTGGTAAAGCTTGTAATTCT GTGAATCCGTTCCCTCCAATTGGATTTGATTAGTGGAAGTCAACTT GGACAGTAATGTACTACCCGGGTTTTTATGCACTCCATAGATCAAA GGATATGGAAACCAAAATTCCGTCGACAATTGTGGTGACTCAAAGA TCAAATGGTGAGTAGTCAAATGTAAAGTACCTTGTGTGGCCGTACC TCTTCTATGCAGCACTACATTAGATACTTTGGCAATCTTGATGTAC TCCATCTTTGCGGAATGGTATACTATTTCTTTTCCCTCTTTTTAGC ACTATTACACCCCGCCCACAAAATAAAAATAATAACGACGACCTAA TCTCACCAAGTGACCCTTGTAAAACCTCCTTTTCTTTATAATGTTT CTTTTCTTACTAATATTTGGTACATTTAGGGTAGTGATAAAAGAAT GGCAACATTGTTATTATTGTGAAAAATGAGGAAAATAGAAAATCAG AAACCCTAAAAAGTGATTTTACCCTATCAGAAATATTCAAATGTCC TAATTAAAAATAGTAAATCCCCTAAACATTCAGATTGTAAACTAGG GTTGAGAAAATGACTCATCCACCACTGTCTTCTTTCCTGCGGCATT CTATAGATTATTGTGAATGACTCTTATTGATGAGATGGCAATAACT TTTGAATATCAGAGATAGGAACCTCCATGTCGTAACGATTGTGTCA CCTTGAGTAAGCATCGAGAAAATCCAATCTTTTTTTTTCCGTCATA AGCATTTCTGCCATGCTATTTGTATATATATAATTACTAATACGTC TTCTATAGTATGCCTTATCTCTTTTTTGAAGCGCTATTTAAGTTTA AGCATCGAAAAACTAACATCTATAGTTAAAATTAGTTCTATAAAGG AAGAGCAATACAGTACATAGACAGGAAGAAAAGAATG >YCL030C Chr 3 reverse complement

(SEQ ID NO: 21) GAATTACGAGAAGCCCAATTGACCATCGAAAAGCTACAAAGGAAAC AACTACACTACAAAAGGCTACTCGATGACCAAAGAATGGTCCTCGA AGAAGTGCAACCGACTTTTGATAGGTATGAAGCCACAATACAAGAA AGAGAGAAAGAGATAGACCATCTCAAGCAACAATTGGAGCTCGAAC GCAGACAGCAAGCCAAACAAAAGCAGTTTTTTGACGCTGAGAATGA ACAGCTACTTGCTGTCGTAAGCCAACTACACGAAGAGATCAAAGAA AACGAAGAGAGAAATCTTTCTCATAATCAACCCACTGGTGCCAACG AAGATGTCGAACTCCTGAAAAAACAGCTGGAACAATTACGCAACAT AGAAGACCAATTTGAGTTACACAAGACAAAGTGGGCTAAAGAACGC GAACAATTGAAAATGCATAACGATTCGCTCAGTAAAGAATACCAAA ATTTGAGCAAGGAACTATTTTTGACAAAACCACAAGATTCCTCATC GGAAGAGGTGGCATCCTTAACGAAAAAACTTGAAGAGGCTAATGAA AAAATCAAACAGTTGGAACAGGCTCAAGCACAAACAGCCGTGGAAT CGTTGCCAATTTTCGACCCCCCTGCACCAGTCGATACCACGGCAGG AAGACAACAGTGGTGTGAGCATTGCGATACGATGGGTCATAATACA GCAGAATGCCCCCATCACAATCCTGACAACCAGCAGTTCTTCTAGG CAGTCGAACTGACTCTAATAGTGACTCCGGTAAATTAGTTAATTAA TTGCTAAACCCATGCACAGTGACTCACGTTTTTTTATCAGTCATTC GATATAGAAGGTAAGAAAAGGATATGACTATGAACAGTAGTATACT GTGTATATAATAGATATGGAACGTTATATTCACCTCCGATGTGTGT TGTACATACATAAAAATATCATAGCACAACTGCGCTGTGTAATAGT AATACAATAGTTTACAAAATTTTTTTTCTGAATAATG >YLR338W Chr 12 (SEQ ID NO: 22) TGATGCAGTTGGAGTCGGTAGCGATGTTATAGGAGGAGGAGGTGCA CTAGGAGGCAAAGGAGGCGCCATAGCATCCGTATGGGGGGGTGGTG CGTTAAAAGCATTCGATGATGTTTGCTTATGTAATTTGGATTCAAT TTCATCCAGAAACGACATACCATTTTGGCTACTCTGTTTAGGCGGG TTTATAGATGGAGAAATAGGAGAAGGTCTTACGTTATCATCCTTAG ATGAACCTATTACATCCTCTTGTTTATCTTGGGTAGTGTATCCAGT ATCACCACCAACCACGAATCTATCATCTCTCTTCTTTTGGATCTCA GCAAGAAATGGTAAGGGTCCCCCAGGTGTTACGGCCGAGGAAGAAC TGGATGAAGATATTTTGGATTGCTTACTGGACGCTGAGGGTTTGTT TGTCGTGAGTGTTGGAGGAGGAGGAGGAGCCGATGGTACTGACGTT GCAACCGAAGGAGGAGGAGGAGGTGGTAGTGGTGCTAAAGGAATAG ATGATGCTGACAAGGCAGAGGATGTTGAAAAAGCACCAGGTGGTGG GGGAGGAGGAGGTGGTGGCGCGGGCATTGACGATGCTTTGTTAGGA GGAACTGATGTAGTATTTGGTAACGGTGGTGCTAAAGTTGGGGGAA CCGGGGTTGCTTTTACGCTGTTAGTCGACGCAGAGCTCATGGCTGC TGGTAGTGGTGGTGGAGGCGGAGCTGGAGCTGAAGTTGCTTTTTTA GGTGCAGAGGTCACATTTGGTAACGATGGTGGAGGTGGTGCAGTAG GCGGTAATGGCGGAGCATGTGATGTAGGAATGGGCGGAGCAGATGA TGGAAGTGGTGGTTGTGAAGGAGATTTATGATTTTCGGTTTGAATC TTTGTGGAAGAAACGCCCTCGACGGCTCCTCGTTCAGACCTCCTGG CATTAATTTCTGCCAAAAATGGCAACCCGCCTGCAGGAACTTCAGA AGATGGTGGTGAGACTGCGTTATCTGTAGGTTTAATG >YIL066W-A Chr 9 (SEQ ID NO: 23) TGAATAAGCCTGTATAACTGCGCATGTAAGAATAGTGGCTGCAATA GATCCCACAGCAGTCAGTGCTCCAGCCTGCTCTTTCAAATCCGTCG TCGTAAGTCTATCAACAGGTAATCGGTCAAATGTGACATTATTTGA GATTCCCAACCAAAATGTGGGGTACCAAAGTATTACTTTTGCTATG GGCGATCCATTTTCTAGTGTTCTTTTCACCGCACTCTTCCAAACGA CGTATAAAACAAAGCATAAAGGTAAAAGTCTTTGAAATCCCACACT GAAAAGCTCATACACGCTAGCTGGGTCATGTGCATCCGTTAGTAAT GGAGGGTCTAGAGATAATACAAGAGTCCAATAGCCCACTATCGTGT TTATCCAGTACCCGTAAATACTGTCATACAAATAAAATATTGGCAG TCCAAAAAGCATATTCAATGCGACCACAGCTGCTCGAGGATCATAA CAGCCCGACAGGATACCGCCTTGTATATCTCTGAATGAATATGAAC CGGGAAAAAATGAATTGAATGCTACTGAAAACCCAGTGTTATACAT TCCTTTTTTTGATGGAAAAGAATTTTGGGCCCCTTGCATAGAAACT TTGGTACAGCCACCGTAAAATGGTGAGATAACACCTGCATGTACTG CAGAGGCGCATGGAAACGAGTCACTTCTATAAGGGTAGGACACGAC CATCGGGTCTTCTTCGCTAAACAGGGCACCTCCGCCAATTTCATAC CCTGTATATTTGACTCTCCTATTCCCTACGGCAATGGCGGAGTATG TCCATCCACCTCTATCACACAGTGCTGGACATCTGATCATGTATTC TTTATTATCAAGTGGACCGCAGTTTTTAGCATTTAAACCACATTCG TTATTGGTACCCTCCCAGTTCAAGTAGGAATTGCAACTTAAAGACA ATATAGGAATCTTTTCTGAGCCATCATTTGGATGGAAGTATGGCGG CTTGATAAGATAGGGGTATATGAGAGAATAAAAAATG >YNL093W Chr 14 (SEQ ID NO: 24) CTGGCTATTTATATAAGATGTTGCTCTAATTCCATGAGTGATGTCC CATCGCATGATGAAGAAGTTATGAATGAAGTGAACAATATCATCGA ATTACAACAACGGCCCATGCAAATGACCAAGTCTACCGTACGTACC AGGAGAAGACCACCACCACCTCCCATTCCTTCCACTCAAAAGCCAT CGTTGACAGAAGAGCAAACCGAAAGTATAAGAATGTCACGCCGTAA TAAAGATGAGAACAATGCTAAAAGAGTTGCCCCACCACCGTTGCCG AACAGACAGTTACCTAACTTAGACGCTAATACTTACTATGTACCAT CCTCACAAAATGACTATGGCATGTATGGTGCTTTCATGGATAAAAA AGCAGATGAATGGAAGAGAAGAGTAATGGACTCAATTCAAAAATTG AGCAATCAAGACACCACATTGATGTTCTTTTCGGATCCGGCATTAA GTTTGGAAGACAGTATTCGCAGAATTAGGGAGAAGTATTCAAACTA AATACACTGTTATTTATATACATCGGGAGGGAGTTTAAAAATTGTA TACACTAAAGTGACCTTATGAATTGGAGCCATTTTCAACGTTTTAG AGTGATGTTGCATCCTTTTCATCAGATCGGGAAATTAAAAAAACGG TTATAGAAGGGCTAAATGTAAATATGTAAATTTTATGAAGTCAAGA GTAAAGAAAATCTTCGGTTGCCGATCAAATACACTCTTACAAAATA CCCTAAACTCAGTTTATCTTTCCATTCCAACTGATTATCGCGTACG CCTTGGTGACCAACCATACCCTAAAATGTCAATTTCCGGGGCGGAA GGGGTCCTTAAACTGCAAAGCCTCTTCCCATGTAAATAAAATAAAT CCGTAGAATTTATTAAATATTGTCATATTATAAGTCGGGAAAGGCC TTCTGAATGCACGTATATTGACCAAATAGAGTTAGATTCAAATTAT TTATTACATTTTTTCAGCATCGAAGTTAAGTAGAATG >YLR381W Chr 12 (SEQ ID NO: 25) GGCGAAAGAGCTGTGTATGAGAATAACGAGACCGGTGTCATTAAGA ACCTGGAATTGCAAAAGGCCACCATCCAGGGTTACGACAATGACAT GAGGCCAGTCATCCTTGTGAGACCTAGATTACATCATTCTTCCGAC CAAACTGAACAGGAGCTGGAAAAATTCTCCCTGTTGGTCATCGAGC AATCAAAGCTTTTCTTCAAAGAAAACTACCCCGCATCCACCACCAT CTTGTTCGATCTGAACGGGTTCTCCATGTCCAATATGGACTATGCC CCCGTCAAGTTTCTAATCACTTGTTTTGAGGCTCACTACCCGGAAT CTTTGGGCCATCTACTTATCCATAAGGCCCCTTGGATCTTTAACCC GATTTGGAACATCATCAAGAATTGGCTGGATCCGGTCGTCGCGTCC AAGATTGTTTTCACTAAGAATATCGACGAATTGCACAAGTTTATCC AACCCCAATACATCCCTAGGTATCTGGGCGGAGAAAATGACAATGA TTTGGATCATTACACTCCACCAGATGGCTCTTTGGACGTCCATCTG AAAGACACCGAGACTCGCGCTATGATCGAAAAGGAGAGAGAAGAAT TGGTCGAACAATTCTTGACTGTCACTGCCCAATGGATTGAACACCA GCCATTGAACGATCCAGCATACATTCAACTGCAGGAGAAAAGAGTA CAACTTTCCACCGCTCTTTGTGAAAACTACTCCAAGTTAGATCCGT ACATCAGATCAAGATCCGTTTATGACTACAATGGTTCTCTAAAAGT TTGAGCCAAGCCACGCGACGCTCCATACTGTATAGACCTTTATTAT AAAAACATCTATTTCTTTATATGTCCCTCTATCTTATTTTTCTTTT ACTTTTATTTGTATAATACGCGAAAAATTATAGAATCATTTATTAT CAAAAACAATCAACTATGAAATGAAAAACAATACGCCTGCTAATAC GGTTCGCCCTTCAATTTTTGTTTTTTTTACATGAATG >YKL159C Chr 11 reverse complement (SEQ ID NO: 26) AGATAAGAATATGAGGGTAACAATGAATGAGAACTCACTTTGTAAT CACCAGTTGAAGAATGGTAAACAAGGCTAGTAATACATCCTGGTAT TTCGGTCTCATGTTCAAAATAATCAGTGGTAATTTATATTATGTAT ATCTTTTCCTTGTTTCTTTGTTAAGCTTTTGTGTAAACATACTTTA GTAATTGTGACGTTTTTTGGCACTTCGCACAGGCGTGACTAGTTTC TGTGAACAGAGGGCGTCTATTCATGATCTTCACAAATCTTGGGGGA GTTAATTTACTCTGCTTCCACATTACATTGATGCGCAGTGATCTAC TGACGCCTGCTGGTGGTGAGTACACATTAGATAAATACCTAGGGTG TGCAGCAATAGACCTTAAACAAGGGTGAGCTTTGCCTATTAGAGAA GAACCTCTAACTGCGCTTTTCAATAATAGCCACCGAACAATTGGCA TATTATGCAACCTGTGTTTTTAAGTACCTTTTTATGTCAGATTTTT TGAACTATCCTTCGATTGTTATTTCTTGATATAACGTTTACATGAT TTCTTAATTTACAACGCGGACGAATTAGATTGAAATTATTTAGCAT ATCTGTCTAAGAGCACATTAGATCGAAGTACCGTAGCACATCTGCC ATACTATCAAATGCATCATCACGAAAAGGCGCAGTGTTGATGGATA GTAAATATGAAAAGGATCTCTTCTTAGGTGTTCCAAGCCTCGCTTC ACGTGTAACATACACAGTTTAGAAGTTTACCAAACCGCGGCAAGGC GCTGTAAGGTTCAAGAGGCTTTGAATTATGCTATCTTACTATCTTG CCGCAAGTTGCTGTCAGGTGTAGTTCCTAGGCGGCTCGTTGACAAG ACCCTTCTGCCCAATGACTTCTATATAAAGTATGGTTTTCTTTTTA AATACAGTAATTCCATGAAAAAAAGAGGGCCAAAAAGATCAAGCAA TAAACCAACCGATATATAAAACACAGAACTGCAGATG >YIL058W Chr 9 (SEQ ID NO: 27) ACAGAAGTAAGTACCGGGGTACCTAAATATACGCATAAAAGTCTCT TTCTTTTTTTTTTTTTTTTTTTTAGCTTCCTACATTTCGTTAATAA TATTATATAGATTATATTTATATTTAAGAAAAGTAATATCAGCATA TTATGAATAGACAAAAAAGTCTAAGGTCAAGATTTATTAAATGTTA GATTATTAAGATTACAATTAACAACATTTGTTGTTACTTCATAAAA TTTCGTTACTTCATAAAAGAACTACAGTCCCCCACTTCTAAATGAG TGGTTGTAGGGGTTCATATACCTCCCATACTGTTGGAATAAAAATC AACTATCATCTACTAACTAGTATTTACGTTACTAGTATATTATCAT ATACGGTGTTAGAAGATGACGCAAATGATGAGAAATAGTCATCTAA ATTAGTGGAAGCTGAAACGCAAGGATTGATAATGTAATAGGATCAA TGAATATTAACATATAAAATGATGATAATAATATTTATAGAATTGT GTAGAATTGCAGATTCCCTTTTATGGATTCCTAAATCCTCGAGGAG AACTTCTAGTACATTCTACATACCTAATATTATTGCCTTATTAAAA ATGGAATCCCAACAATTATCTCAAAATTCACCAACTCTTCACATAC ATACCTGCGGTAGCAAGATAGGTACACTTTTTCTACGTTTCACGAA GGTAGCGATAGGTACCTCACTCATTGTAGGTGCGGGGGTAGCGATG GAGGTTTCTGTACCATTACCACCACAGCCACTATACTCACGTAGTG AAGTCCCTAGCGTGGAATTGTGTGGTATCGTTGCTATCTGTCGTTC GCCACCCTCGGTATATCCAACGTGCAGGCCAATATCACTCTCTAAG AAAATCGTATCAGGATTGGTACGGACAAACTCTTCATAGCCTACGT CGAAATCAAATTCTGCTAAAGCTGTGACTGTAGTTAAACCTAAAAC CGCGATTATTGCTTGAAAAACTGTGGAGAAATTCATG >YKR037C Chr 11 reverse complement (SEQ ID NO: 28) TGTCATCGCCGCCAGAACGTGCTCCTTACTGTGGGACGTGCCACTG GTGGGAGTAAACCACTGCATTGGTCACATCGAAATGGGGAGAGAAA TCACTAAAGCTCAAAATCCTGTGGTACTGTATGTAAGTGGTGGAAA TACACAAGTTATTGCATACTCGGAAAAAAGGTACCGTATCTTTGGT GAAACGCTTGATATTGCTATCGGTAATTGTCTTGATAGATTTGCAA GAACTCTGAAGATACCTAATGAGCCCTCGCCTGGCTACAACATCGA GCAGTTAGCTAAAAAAGCCCCTCACAAAGAAAACTTGGTAGAACTT CCCTATACAGTAAAGGGGATGGATCTTTCGATGAGTGGTATATTGG CTTCCATCGATTTACTTGCCAAGGATCTATTTAAGGGCAATAAGAA AAATAAGATCCTATTCGACAAGACAACGGGCGAGCAAAAAGTCACT GTAGAGGATCTTTGCTACTCTCTGCAAGAGAACCTATTCGCCATGC TAGTTGAAATAACAGAAAGAGCTATGGCTCACGTTAACTCCAATCA AGTTTTGATCGTAGGCGGTGTTGGTTGTAACGTGCGATTACAAGAA ATGATGGCGCAAATGTGTAAAGACAGGGCCAATGGGCAAGTACATG CTACAGATAATAGGTTTTGTATCGATAACGGAGTTATGATTGCCCA AGCAGGACTACTAGAGTATAGAATGGGTGGGATCGTGAAGGACTTT TCTGAAACTGTTGTTACGCAGAAATTCAGAACCGATGAAGTATACG CAGCCTGGCGTGATTAACGATTTTTGTTACAGTTAGCCTAATGTTC ACACTACGAATATATATATATATTTATATATGCCATACACCTTACA TTTACAGCTCAGTGTATAACCTTGTGGAAGCGCGAAAATAAGCAAG AGACATTTGAAAATAATCAATAAACAAAGCTCAAAAAAATTAGATC ATCACCTAACAAAATAAGACGTGGCAATTACAGAATG >YNL279W Chr 14 (SEQ ID NO: 29) GGCAACATAGCAGTACGTCGCCAAAAAGAACGAAAACAAAATAGAT ATTATGCATAAACTAACGTGATTTTCATACAGATATTGCAATTCAG GCAATTGTCCATCAGTCAATTTCCATCTGATAGCCAAAACTAAGAC CAAAGTTGTAGACATGGCAATTCCATTGATCTTATACGAAAGCTTC GAACCATCCCTTAACTGAACACCCTTCATGACTCTGCCCGGTAAAA TGACGTCCAAAACTGCCAGTATTCCATACCACAGGCAATAGACAGT CCATAATTCACGATTGCCCAGATAGTAGCGCAATGGCTTGATACCG TTCCAAAGCTCAACTATATCGAAATTCTGGAAAAATCCCTTAATAA AATAATCGGGCCTTATCATTTGATTCAAGATGATAGTGAAAACAGG CAGCCCTATGCTGATGCCTAAGGCACCAATCAGCCCACCAAATTCA AACTCTGTAGTTCTGGGATTCAAAGCTGATACCATCCTTTTATTCT CTACACCGAATTTGTCTTTACTCCTATGCTGTTTACAAGGTCTATC TGATAAGCAATTGCGCAAGAAAATAGTAGAATGAAAACTGATTATT AAAAACAAACGTAAACTCAAGCCTCACTTGATGCTCAGACGGAGTA CGTGAAAAACGTCCGTTATGCAAAACCCTTTATATGCACAACCTTC ACACAATGCAAATTTCCGATGATGCCTACATACAAAAGAGCGAAAG GCGATATAAATTTTTTTCACGGGATTTTCGTTTAGGTGAAAATAAA ATGAACGACAGAGCATGCAGAGTCCGGGTAATACATATGTTTCAAT ACTGTTTCAATACTGTTTCAGAAGTGCGTCACATATTAATTTTAAC TTATAACTGGCCTGTTGCTGGCAAGAGGTATATATATATGACGAAT GTGACCAACATAAGTCCTTAAGATAATCCCGAAATATTTGGTTAGG ATGATTCCCTTTCGAATTTGTGAACGTTGATGATATG >YOR032C Chr 15 reverse complement (SEQ ID NO: 30) CTAGCGGTCTACATTCGCTATCAACTGAACGAATAGTGATGCAATC TGAACCTTAAACTTTTCGCTCGCTTTTACTTTCCAGAAAAAATTTT CTTCATTGGGATTCCTCTGCTGACAAACGGGCTCACAGAACTGAGG AAACGAGAATTTTGTTAATCAAAGCAACATTACGGGAAGGAACGGA ACCGTCTCGTTGCTGTGGGCGCGAGTTCGACGCAAGAAAAAAATGC TGCAGCATCGTCTTTTGTGAACGCCAAGAAGGAGTCCGGCGAAGGT ATTGGGCGTCACAACCTTTTATTCTCCGCAGTGTCTCTTGCCTACA AAGCCTGCAGAAGCTTTTATGCCGGGGTGTACGTATGTTAATCAGT TACCCTTTCCTACTGTGTGCCGCACCCCTCATTTGCTCTCGATACG AGAAGTTCCGCGCCGATTCTGGCCTTTTTGTTTTCTGGCTAGCCTA CTTTCAGGGGACGTGCCTTCTTATGCCGCTGTAAATTACAGCAGAG ATTTAGATCTGAGTGAAAACGTGGCGAGGAAAAAGGGTACACCGTT AAAAGCGTAGACACAATCCCACTTTGTTGTGCCTAGTCTTCTCTGC TGTATTTTAATTTTCTGTTTGAACTTTTTTCCGTTCTTTTCCATCA TTGTTTAATTTTTACTTTGAGTGGGCTTCTCAAAAGAAAAAAATAG CTGGTATTGTATTTTTACCGTAGGCGTTTTCTTTGTATTTTTCCCA AGAGCAGCAGCACCTTTTATATACCTTGGTTACACATTGTAAGCCT CAAAAATCGTCCTATGTAAGTGTCTTATCGCATCATACTTAAGGTC AAACCTGTAAAGCGCGCTTCTAGTTTTATTTCTACTACTCGCCTTG GCTCTCGAGATCGCTTAGGTAGTTTAATAGTTAGTCACACCCACCC ACCCATTCGCTTAGAATATAGAATATAGAGCAGTTGCAGTACACGA CTCATTTTAGCAACGATAAGAGTATAAATTGGAAATG >YML058W Chr 13 (SEQ ID NO: 31)

TCCTTATAACCTGTAAAAAAAAAAAAAAAAAAAAAAAAGAAGGGTT TAAATAAAAATCGGACTTACTCAAAGGGTTGAAAAGCACTTTAATA TAGGTTTTTAGTTTCGGGTAAGAAGATGTGTCAAAGGTCTCGAAAA GGAAACATTAGGGCAAATACGTAAAGGTTGCCTTCGTATCTCGTTT CCACAGCAACGAGAAACGAGATACGAAGGCAACTGATTCCCAGCAT ATAAAAGGCCATGAATTTTTGGCGTTTCCTATTGTCTTTTCGAAAC TATTTCTTTCATTCCTTTCCTTTCTTGTTCTTTTACTTATAAGAAA AATAATATACGTATATATATAACTACAAACCACATCAGCAATAAAA AAAAACTATATGACCATGGACCAAGGCCTTAACCCAAAGCAATTCT TCCTTGACGATGTCGTCCTACAAGACACTTTGTGCTCAATGAGCAA CCGTGTCAACAAGAGTGTCAAGACCGGCTACTTATTCCCCAAGGAT CACGTTCCTTCTGCCAACATCATTGCCGTCGAACGTCGCGGCGGTC TTTCTGACATTGGTAAGAATACTTCCAACTAAGAGCATGCTTCTCT TTTTTTTTGTAGGCCAATGATAGGAAAGAACAATAGATTATAAATA CGTCAGAATATAGTAGATATGTTTTTATGTTTAGACCTCGTACATA GGAATAATTGACGTTTTTTTTTGGCCAACATTTGAAATTTTTTTTT GTTACCTCGCGCTGAGCCCAAACGGGCTCCACTACCCGCCGCGGTC GCCATTTTGGGAAGTCATCCGTCCCAAAAAGGAAATAGCCATAACA TATCGTTACTGTTTTGGAACATCGCCCGTTTCGCCCGATTCCGCCT CAGCGGGTATAAAAAGAGATCTTTTTTTTTCCTGGCTGTCCCTTCC CATTTTTAAATGTCTTATCTGCTCCTTTGTGATCTTACGGTCTCAC TAACCTCTCTTCAACTGCTCAATAATTTCCCGCTATG >YMR303C Chr 13 reverse complement (SEQ ID NO: 32) AATGGCAAACTGAGCACAACAATACCAGTCCGGATCAACTGGCACC ATCTCTCCCGTAGTCTCATCTAATTTTTCTTCCGGATGAGGTTCCA GATATACCGCAACACCTTTATTATGGTTTCCCTGAGGGAATAATAG AATGTCCCATTCGAAATCACCAATTCTAAACCTGGGCGAATTGTAT TTCGGGTTTGTTAACTCGTTCCAGTCAGGAATGTTCCACGTGAAGC TATCTTCCAGCAAAGTCTCCACTTCTTCATCAAATTGTGGGAGAAT ACTCCCAATGCTCTTATCTATGGGACTTCCGGGAAACACAGTACCG ATACTTCCCAATTCGTCTTCAGAGCTCATTGTTTGTTTGAAGAGAC TAATCAAAGAATCGTTTTCTCAAAAAAATTAATATCTTAACTGATA GTTTGATCAAAGGGGCAAAACGTAGGGGCAAACAAACGGAAAAATC GTTTCTCAAATTTTCTGATGCCAAGAACTCTAACCAGTCTTATCTA AAAATTGCCTTATGATCCGTCTCTCCGGTTACAGCCTGTGTAACTG ATTAATCCTGCCTTTCTAATCACCATTCTAATGTTTTAATTAAGGG ATTTTGTCTTCATTAACGGCTTTCGCTCATAAAAATGTTATGACGT TTTGCCCGCAGGCGGGAAACCATCCACTTCACGAGACTGATCTCCT CTGCCGGAACACCGGGCATCTCCAACTTATAAGTTGGAGAAATAAG AGAATTTCAGATTGAGAGAATGAAAAAAAAAAAAAAAAAAAAGGCA GAGGAGAGCATAGAAATGGGGTTCACTTTTTGGTAAAGCTATAGCA TGCCTATCACATATAAATAGAGTGCCAGTAGCGACTTTTTTCACAC TCGAAATACTCTTACTACTGCTCTCTTGTTGTTTTTATCACTTCTT GTTTCTTCTTGGTAAATAGAATATCAAGCTACAAAAAGCATACAAT CAACTATCAACTATTAACTATATCGTAATACACAATG >YJL153C Chr 10 reverse complement (SEQ ID NO: 33) TTCTTTTTTTTTTTTTTTTTTTCTTTTTGGGAACGGGGGAAAAGGT CTCACTAGTATATAAAGGAAAGAGAGTACAGCACGAATGAGCCAGC TGCAGGAAAGGGGCTAGGTTAAAAAATAAAAACCCAGCAGAAAGCA AACAACCAAATATAATTTAGAAATGGACAGAGACCATATTAATGAC CATGACCATCGAATGAGCTATTCCATCAACAAGGACGACTTGTTGT TAATGGTTTTGGCGGTTTTCATTCCCCCAGTGGCCGTCTGGAAGCG TAAGGGTATGTTCAACAGGGATACACTATTGAACTTACTTCTCTTC CTACTGTTATTCTTCCCAGCAATCATTCACGCTTGCTACGTTGTAT ATGAAACGAGTAGTGAACGTTCGTACGATCTTTCACGCAGACATGC GACTGCGCCCGCCGTAGACCGTGACCTGGAAGCTCACCCTGCAGAG GAATCTCAAGCACAGCCTCCAGCATATGATGAAGACGATGAGGCCG GTGCCGATGTGCCCTTGATGGACAACAAACAACAGCTCTCTTCCGG CCGTACTTAGTGATCGGAACGAGCTCTTTATCACCGTAGTTCTAAA TAACACATAGAGTAAATTATTGCCTTTTTCTTCGTTCCTTTTGTTC TTCACGTCCTTTTTATGAAATACGTGCCGGTGTTCCGGGGTTGGAT GCGGAATCGAAAGTGTTGAATGTGAAATATGCGGAGGCCAAGTATG CGCTTCGGCGGCTAAATGCGGCATGTGAAAAGTATTGTCTATTTTA TCTTCATCCTTCTTTCCCAGAATATTGAACTTATTTAATTCACATG GAGCAGAGAAAGCGCACCTCTGCGTTGGCGGCAATGTTAATTTGAG ACGTATATAAATTGGAGCTTTCGTCACCTTTTTTTGGCTTGTTCTG TTGTCGGGTTCCTAATGTTAGTTTTATCCTTGATTTATTCTGTTTC ATTCCCTTTTTTTTCCAGTGAAAAAGAAGTAACAATG >YLR092W Chr 12 (SEQ ID NO: 34) CGCTCCCACGACATGCGCATCTCTTCCAAAAACACTACCACTTTCT ACTGACTCACTGGCCATTTGAGAACCACAGAGACTTGGTAGATTCC ATCGCTGTAAACAATGGGAAACTAAATTCAACGTCTTCAAGGAGCG TCTGGCTGAAGGCGGATTGGATAACACTGTTTAACGTTAAAAACCC TTGGGTCCAAACGCCGCCATCGTTAATGCGTCTGAGTGGGACAGAT CTTGATACCTTCACACCAGAGAGGATATTCCTGATAAATTCTCTTG GAAACCACTACAAATTTTTAATAGCGAACAGTCATCTAAGCTACAA TCACAAAAAATACCCCTCCCCTGGCGTGCAAATTCCTGTCAGGAAC GCTCTTGGCGAAGTTTCTCCGGCCAAACAAATTGCCCAACTTTTCG CAAGACAGCTGTCTCATATTTACAAGAGCCTCTTCATAGAAAACCC CCCGCTCTCTCCTGAGAACGAGCTGGCATTGACTGCCGTCTTCTAT GACGAGACTGTAGAGCGACGCCTTAGAAGGCTCTATATGCGAGCTT GTGCAAGGGCATATACGACTACTAATGCCGACTCCACCACGGAGCC TTTGATGTTTCATTGCACCCGGTGGGAAGTTGATTAGTTGTTGTTG GCTGTTATACTGGAGTAAATGTCACGTGCCACTGTGGCCGTGTCAG GTCACGTGAAGAGAGAAATTCGGCCACAGTTGTGGTCCTAAACAAG GACTGAAAAAGATCGCAGAAACTAGCAACGTCGGATAGCGGTATGG TTGAACCAAAGTCCAGTTTTTAGTCATAGCCGGTTGAGGGATGATC TGCCGTTCAGTGTTCTGCGTTCAATAATACGCATATATATATATAT CAAGGTATCAACACAATACTTGAACAGGTTAGGCTCGTACTAAAGC CTGGAAGTTTTTATCTTTCTGTAACATTTTTCTTTCTTGAGGTGTG TGTGTGTATAGATTAGCAGGGAATTATCTAAGATATG >YFL052W Chr 6 (SEQ ID NO: 35) CGACTAACCTTTTTCTTGGCAGTATGGAGACTGACTAGGTCTCCCA AACATTCATTGTAACTGCTGTTTAAAGATTTTGTTCTAACCTAAAT TCAAGTGAGAAGCTGAACATGTGTCTCTACTTATGATATCACGACA GCAAATACTAATCTTGCCATAAATAGTCTAGCGTTTTGCAACTTAC CTCTAGATATATTTTATTTCTTGAGGAACCGTTTTCGTCGGTAATA ACAAAATACTACTGAAACGCCACAGCATTGAGAGAATACGTTATCG ATTACGGCTTTCTTCTCGCTCCAGATGTCGCGGGTAAGATATTCAC CTCAAACTTTTCTTGTTGAGTGTCGTCACAAATCTAGAACCTACAT GCCATCTCAACGATTTTTCTGGAGAAAGGCCTCACTCCGTTCCGTA CGTAATGCATAGATAAAGTATCAGGATCTTCACGATGCTCGAGAGT TACTTAGTAGTCTGAGTTTATGCGAAAAAAACTCCGCCGTTGTAAT AATCGGGAATACACAGAAGTAGTACTGCACTATCACTGGGATACTC AAAAACCTTCTTTTTAACTTTTCTATCCCACAAATAGAACATAGGA AAGAACATTGACTCCTCCACTTGAAGTTAAATTACAGGAACAAACG CCTAACTATAATTTCGACATTGTTGCATCAACGAATCGACCGAAAG AAAAATCTGGAGTTGCAGTTATCACTTGTATGTGCACTAAGATTTA TATTTTTACTCCTGAGATCTGCCAAATCGGTAGCTTATTGAACTGC GTTCCTTTTTCCCCTGAGTTCTCGAGGTACCTGCGGCTTTGTCTGT GCCATCTCCCCCACTTTAAAGTACCCCACGTTACTACCGCGTTTTT CCCCACCCCCGGCTTAATAAATTAGCTATATCTTGTTGACTTAAAT ACGGAGAAAAGAAGAAAACCTTCAAGAAATGCTTCATTGTCTTGTC AAAAGAGCTAAAGTAAAAGAGCTCTAGTTCGAAGATG >YIR017C Chr 9 reverse complement (SEQ ID NO: 36) CTGTCGAGTGCTGGTGGCGCTTGATAGCGGTATTGTACTTAATAGG TATCGCCTTCATTGGTTTGAAATTCTCGATCAAATTCTGCAGGATA GGGTCCTGAGCAGGCACAGAGGCTTGTTTCAGAGTAAGGGTCTCCA ATTTCTGTTTAAGGGCATGATTTTCCGATTCTTTCGCTTGAAGTTC ATTTTGGAGGCGGTTTAGTTTCGTTTCGTAGTTTTTAACGACCTTA CTCAGTGACTCTATGGTTTCCTCCAGCACTTGCAACTTGTTGTTTT TGCGTTCTCTGTAGGCCCTTTGGGCGTCTCTATTCTGCCGTTTTTT CTTCTGTAGCTCCTCATCATTTTCTTCAGTTTCGTAATCTTCGTGA AGTCGATGAACTCTTTTCCTCCGCTGAGCTGCTCTATGGGGCAACC TTGGAGGCAGTTTCCAATTTTTGGACACGTGGATCTTGGACAAAAG AGCGAGGTGGCTTTCCTCAGACTCCTTAGGTTTTATCAGAGGTAGA GCCATGACTGTGATAATATGCTAGTTACACTGTTTATGTTGTGTGA ACTTGTTGTAATATGGTTAACTTCACTTTCAGTGATTGATATGATA GCGACATCACTGCCGTGCAAAAAGACCATTCCATTACTGCACCTTT TTGTCCTTTTCCGTGGAATAAAAGTTCACTCGTCAGTTCCATGCAT TCTGGAAAAAAATGATCTGAAAGATGCCACAGTTGTGGGGCCCGCC CGGCCCAATAGGTAAACTAAAATACAATAGAAGGGGTACTGAGTGC ACGTGACTTATTTTTTTTTTTTGGTTTTAGGTTTCGCTTTTTTCAC CTTTTTCTACTTTCTAACACCACAGTTTTGGGCGGGAAGCGGAAAC GCCATAGTTGTAGGTCACTGGCGTGAGTCAAGGCCGGGCAGCCAAT GACTAAGAACACGAGGTAACTTGAATTTAACTATTTATAACCAGTG GTAGTTACGAAGACAAATTGTTTTGTTCGTCAATATG >YLL062C Chr 12 reverse complement (SEQ ID NO: 37) CAATTTTGAAAATTGACATATAAAACTCTGATTCTGCAAAGCCTCT TGCCCCAAAAAGATTCAATAGCATGCTTAAAACGAACGCGATTGCA ACCCAGGCAGCAGGATTGACCGATGGTGCCCAATAAGAGATGGTAA GCGAACATCCTACCAGCTCGCTAGGGTAAGATATGAGCCACATCAA TAAGTAGTTAATTCCTATACTGAAGCCGACTGATGGGTCTATAAAT CTACTGGCGTGCAGCGCATAGGAGCCGGAAACAGGGTACTGACATG AAAGTTCGGCCCCACACTGAACAACACAGAGCATAGATGCGCCGAC CAACAAGAAACCAATTAGCAAAGAAGCAGGTCCGGACGCTAGTGAT TCCCCTAAACCAATGAAAAGACCCGTCCCTAGAGTACCTCCAATGG CTATCATGGTCAGGTGTCTTTGATCTAGGACCTTTTTATACGGCTG GTTGGCTAAGTCCCATTGTATTTTTTCTTCCTCTGAAAGCTCCGAA TACAGCAAACCTTCTTGGATCGCTGGTGAATCATTTCGCTTGAAAG AGTTCTTGAATCTGTGTATTAGATTATTTCCTTCATTCGAAGGCGT ACTTAACACGCTAGTGGAAAACTGAACCTTCGAAAGTTTGGTAGAT TCAAATTCATCCATTTCGGGTATCTTTCATGGTATCCTGATGGAGA ACTCTTGACGGTGATTACTTAACCACCCAAATCTGTAAAATATATA CGCATTTATTTCCTGGCATCTCTTCGCTATCCCCGCAAAAAGTTAA TGAAAAAAAGCCATTCCTGCAGGAACTGTGGAAAAGTAAAAACTGT GGCATGAAAGTACTACCAAATTGTGGCGAGGTATTCAATGGTAATA GCAAAACAGCAACAACGCCAATTTGAAAATGTACTACTAAGGAAGA TAATTTAAACAGACAAGTTGTAGAAGAAATCTGAATCAGCAACTTT TAGTGTGCAACTTGAAAAAGTAATCAAAAAACAGATG >YMR323W Chr 13 (SEQ ID NO: 38) CAGTTTTCTTTTTGAATGAAGGAGAAAAGTGTTCTAGAAATATGTT TTAGTTCTAAGTATCGTTGTCTGGAGCAAGCAAAGAAAAGCAGACC TGTATGTGCAACTTTCTTGTTTTCCATTAAAATCTCAAGAACCGGC CCCTTGACTGTGCTCATATATCAAGTATCGGTTTTAAAGTCCCCTA ATTGTGATAATTGCAAGAATGACAGTCAAAAAGATATTTTTCTTTT CTTTCTTTTTACCTATCCTTCATGAAAATACCTATGCTGATACTGA ATATCTTCATTTGCAGCTATGCAATATTTCAGATACTGCATTTTAC CCAAGAGTTTCTTTACTGGTGGTTGGATTTTTTTTAAGACGAGAAG ATTACCAGTCCTGGATGTTCATGAATGTGCCTATTGCGTCATCAGC GACTCCGCGCCAAGAAAAGAAATACTCGCATGCTCGGATTTATAGA ATCGCATAATGGAAATAGCTTCCTTAAAGGATGGAGATAAGGAAAA AATGACAAGAACAAGGAAGTACTTGGGAGCTTTCTCCGACATGTTA AATATTTGAAACTCACGCAGCTCTCCTGGAAAGTTGCATCTGGAAA GGTAAGGTTGTTTTTTGTTCAGACATCAAAATCGGCTCTTGTAGAC AATGTCACAGATCCACAAGTTGAAAAAAAAGTTTCGATGAACTGGA TAAGGGGAGAGGTCACAAACAAAGTGTAGGGGGTGAGTAGTATAGT GGTAACTTGTTCATTTACCTAAATAACATTCTCACTAGAAAAGAGA TATTGAAAGACTCCTCGTTTACCTAACTTGGCTGGTTCTTAGGTAT ATAATAGAAACATGGATCTGGCAGGTTATTACTTACAGTTTGCATT CCCACCAGGTAACAATTTTCATTATATATAGTTATTTTTTACCACC ACTTCTTCTTCTTTCACTTTGTCTTGCAATAGAAATACCAAAACAA GGTGAGGAAAAAATCGAATCTCAACGATAAAAATATG >YPL171C Chr 16 reverse complement (SEQ ID NO: 39) CGGTTGGATCCTCACTTGTTTTAACACCTCCAAATAACAAGTTTTT AATGAAGGACATTTGTTCTCTATAATATTCCGATGTACGTGTGTGT GGCTGATGAGATTTAGACTGGTTAGACTATTTGACGCGTCTATTAT AGCTTACTGCAACAAGAAAATGATCGTTGATATATAAACTCTCAGA TGTATATATCGTTCTGGAAACATCGAGCATAATACAATACAATTCA ACAAAAATGCGAGAAGGCACTGATGTCTTGTCGTTAAAGAACCAAA AACGCGGACACTACGACCGTCTTATTTCCGGTAGAAAAAGGGTACA TACAGTTGAAGGAACGAAGAAAATTAAAATTAGAAAAAAAAGTAAA ATAAAACAAGGAAGGTAGGGTAATATGGTCTCGTTTCCTTTGTCGC TCCGCAAATAAAGGAGCTTATTCCCGCACGCTCACATGGTAATTTG CGCCAAATCACGGATGTGGAAAACTGATCACGTGCTTCGATCGCCA ACTACTGAGCGTCGTCCCACACTGATCTGGCACAGCTTACCTCGCC TTGAAAATTTTAATCTGTCCTGCTCGTTTGTTGTATATTGCTTCTT CTCAGAATATGCCCGCGATAACTGACAAAGAGGGTTCGACGTTTCA GAGATTCTACTCTTGACCACTGTTTCGTGTAGCCGCTCAAGGTTTA TTTCTTTCTTCTTTAATGTTCTTGGCACTTAGGCGGCTCCGTCCTC CGTCTGAAATTGCCGATCCTATTATTTGCGGAGGGCTCCTTAGAAG GGCTCCTTAGTAAGCAGTTTGCGTTCCTGATATAACTCCGTTCAGA ACAAGGATAAAGTCGCAATAACCATTACTAAGCACAGTGTTGTAAG TAGGACAACTCGAACCTATATAAGGGTTGTGAACTGTGCTTGATTC TTGCCCATCATATGCAAAAAAGTACGTACTTGATATATACAACAAC TGTAGTTCAGTATAGCGAAGTTTAAATTTAGAAGATG >YER065C Chr 5 reverse complement (SEQ ID NO: 40) TGGAAATGTAAAGGATAATGAGTGAGCATATAAAATGGAAGAAAAA ATAATAATAGGATTATGTATAAAATATCGATTCCCTTTTGTAGATT TCGAGATCTTCGAGGAGAACTTCTAGCACGTTGTTTACATATCTAA TGTTGTAACACGGCCTTTGTTATCTTGTGAATATATCCATCACCTA CGTCGCTTGAGGTTTCGTATCAAAGAAAGAGAGTTCAAACATAATC ATACGTGTTTCACTCCAAATTTGATCACAAATGGCCACCCATTATA GCTTGTTATTATTTACTTCTTCTTGAGTTCATTTTATTGAAAGATG CCCGCTGGGAACAAAACATAAATAAAATTCAAGAGTACAATATAGC GTAGCATAGTTGCGAGCAAGGGAAGGCAACACAGTTAAAATGACAA TGTTAGAAGGAAAAACTAAATCAAGCTCCCATAGGAAATTTCTTGT GTCAGTAATATGTCTCGAGAAAATAATAATAATTGAATCTATTTAT TGAAAAGTAAATATCTCGTAACCCGGATGCTTTGGGCGGTCGGGTT TTGCTACTCGTCATCCGATGAGAAAAACTGTTCCCTTTTGCCCCAG GTTTCCATTCATCCGAGCGATCACTTATCTGACTTCGTCACTTTTT CATTTCATCCGAAACAATCAAAACTGAAGCCAATCACCACAAAATT AACACTCAACGTCATCTTTCACTACCCTTTACAGAAGAAAATATCC ATAGTCCGGACTAGCATCCCAGTATGTGACTCAATATTGGTGCAAA AGAGAAAAGCATAAGTCAGTCCAAAGTCCGCCCTTAACCAGGCACA TCGGAATTCACAAAACGTTTCTTTATTATATAAAGGAGCTGCTTCA CTGGCAAAATTCTTATTATTTGTCTTGGCTTGCTAATTTCATCTTA TCCTTTTTTTCTTTTCACACCCAAATACCTAACAATTGAGAGAAAA CTCTTAGCATAACATAACAAAAAGTCAACGAAAAATG >YDR114C Chr 4 reverse complement (SEQ ID NO: 41) TTCCTAAGCCTTTGAGATATATCAAAATTGCTGCCTTTACCAACGA

CGAAAGTAAATTGGAAGAGCTTCGTGAGAAATACCCAAATCATTTG ATTGGCGGAGCAGATCTTGTTGCCAAAATTAAAAGCGGTGAAATTA GCGTTGATTTTGACAAAGCATTTGCAACTCCTGATATTGTTCCAGC TTTACAATCGCAGGTGGCCAGGATACTTGGTCCTCGTGGGGTTTTA CCCTCTGTCAAAAAAGGTACGGTGAGTGATGATATAAGCTCCTTAC TTCAAGAAAGTCTAGGATCTATGCCTTTCAGGCAAAGGGGAAACTC TATCAGCATTGGAGTCGGCAAATGCTACTTCACTGATCGAGAAATT TTACAAAACATTATATCCGCTAGAGCGGCATTTAAAACTGCTGTTG ATAATCAAAAATCTAAGAAACCAAATATACTGAGTAAAACCACATT ATCAAGCACACATGGCCCCGGTATTGTAATCGATTTTGCTTAATCA GCGAATCAGTTTTGTCTTGTTGGACTTTTTTAATTGTATATATATA TATACTGGTGCATTTTCTTTCTTTTTATATAAAATCATGTACATAC AAAGTAACCGTCTTTTTAAAGTGGAATAAAGTAACTGCTCTTTTAT TTTTGAATAATAGTGAAAGTGTATGTTGCATAATCATTAGATACCT ATGTACAAGAAGTATTCAAATTTATCTGAATAGTATGTGAAATTTC AATGAGACAAAAACCACCTACCTTTGAGCTTCCTCCTTTTCAATAT CTTAGAGCCCTGTTTGCTCTTGGCCCTAGCCAAGAAACCAAAAGTT CTCTTCCGTTTCAATGTACTAGGTTGATAGGTGTTACCCCTTGATT TCCATCTTCTTTGACCTATTAAGCCAAATCCCAACGGTGTGAAGGA CGGAGTCTTCAATGGTGAACTGTTTAAGAGCATACCGGTTTGTGGG CGTAACACAGATAGAGCAGAGAAAGAAGATATAGATG YBL065W Chr 2 (SEQ ID NO: 68) CGGTCCAGAAAAGCAACTGAGATTGGGAGTATAATTCGGTGGCGTT ATTGGAATACATAATAGGAAAATACGGCAGATACCTAGTCACGAAA ATATGGTGTAATCTATTCGCTTTTTCAATGGAAATACTAATATCGC CCAGTACAAACTCATCTACATTTGCATGCGGCGAAGGCAATAATGG CATAGTCGTGGTGGTGGCTACTACCGGCGTCTTCGTCCTATCTGCA TTGTTATTTGTTGCTACGTGGCTTGTTGCTGCAAATGGTGGTTGAT TTGTTGTCGTTGTAACGGTGGTCGACGTAGTATGAGGGGAATATGT TTTTTGAATTGGAGAGAAGGGGCCGTTCGGAGTGTTACCTGCAGAG TTGTTCTTATAAAAAGCCATTTGCAAAGCAGGAGGTAAAGATTCTT TTGAATTATTAGGCAATGCTGAGTCATTTAGCAGCGGGGGCAGCTT ATTTGGCTCTGTTGCAACCAAGCCTTTCGAATCTTGCGCTAAAGAA GATGCGCGCAACGTCATGTGAGAAGATGCTTCATTATTTGCTTTAA ATTTATTCGTATTGCTGCCCTGATTTGCTTGTAAGAGTTGGGGTTC CCTGGACAAATAAGTTTGAACTGAAACCTTAGAATCTCGTTGAGCC GCGGAAGAAGTTGGAGAACCTGAGGAAGGAGAAGAATCTGGGTTAG GGATAATAGTACCCGGAGTTGGAGTTGGATGCAGATTGAGCTTATT CAAAAGGCTATTGCCCATGGGAATCTGTTGTAAAAGATGAACGAAA ACGCTGTCATTGGCCAGAAGAGTATCGAGTTTAGATTTGATTTCAT CCACATCTTGTCTCAGTAGTTGCAACTGTGAGCCCTTCTTAGGCCT GAATTGAGGATTGATTTCACAGTGGAGACCAATTTTTTCGCATCTG GAGCAAGGATGAGGGAAATTTTGACTAGCATCGCATTTGATTTTGT GCTGTCTACAATGTGTACATG

TABLE-US-00004 TABLE 3 Baseline promoters identified Affymetrix S. cerevisiae Probe ID Gene Synonym Proposed function 4464_AT YHR082C KSP1 Serine/threonine protein kinases 6604_AT YDL126C CDC48 Microsomal protein of 7242_AT YBR106W PHO88 CDC48VPAS1VSEC18 family membrane protein involved in inorganic phosphate transport 10388_AT YLL043W FPS1 Suppressor of tps1Vfdp1 7639_AT YPR108W RPN7 Regulatory particle of the proteasome 4130_AT YIL041W 11172_AT YJL166W QCR8 Ubiquinol cytochrome-c reductase 6311_AT YDR165W 9999_AT YLR330W 6540_AT YDL058W USO1 Integrin analogue gene 4531_AT YHR012W VPS29 10644_AT YKL053W 10766_AT YKL196C YKT6 v-SNARE 6583_AT YDL103C QRI1 9874_AT YLR427W 10368_S_AT YLL020C

[0104] Baseline promoters identified in the experiments set forth above are as follows:

TABLE-US-00005 >YHR082C Chr 8 reverse complement (SEQ ID NO: 52) TCTAAATATCGTCCCGTTACCCTCATCGCTACTGCCGGGCGTTCCC AACCCCTTCCGAGGCAGATTATATTTATTTATCTTTTTAACAATTT GTCCCTATATAGGCGGGCCGAACACAGCACGTGAAAGAACTCTCAG GCTTCCACAACAGGCCATATCAAGTCCACACTTCCCTCATTACTAG CATTTTTACACAAGCAGTCCACGCATTCCGCAACAGTGTTCACCTT TCTTTTCCCTAACTTATCTTATTATTTGTTTGTTGATCGCAAACAG ACCCTTTTTTTTGGTGAGCGCATTTTACACAGTCTCAAGTGTCCTC TACTATAAAAATACAACCTCAAACAGTACTTACTGGCGTCCGCAGA ATATTACTGCACTCTCAATCTGTAAAGAATATAACAAGTGACCCAT TCCCTTGTTTTATTCAACTTCGAAATCTCTCTGGCTATCTTTGCAT GCTTATCTAACTTTCACGTGACCCGGATATTGTTCTCTGCTCAAAA AAGAACTGCAAAGAAGGAAATAGAAAAATAGCATACAGGCTCAAAG CTATAGTTTTCTGAAAAGGGACACCACGAATACAGTAGTATCAAAG AGAAAAAAGACTTCTTTATACTTACAGAAGGTTCATTTTCTGATTC TACTCTTCCAATCTAGTGTCGCAAAAAAACAAAACTTACTGGTATT AGCTGGCAAAAAAAAAAAGAATAGGTTATAATTAAAGACATCTTTT CTCTATAAATTTTTTCTTAGAAGAAAAAGCCAAAAAAAAAAAACCT GCTTCATACCCGCCATCAAATCTTATAGGCCTTATAGACTGCATAT TACCGGATTCTTTCTCTCCGTTAACCCTACTATTCTTTCACTATAC TTTAACCTAAAATAAAAAAGGAAAAAAAAAATTAAAAACTTCCAAA AACTTAGAAATTTCAAATACAAAACAAAAAGACACGTAAAGTTAGT GCAATATTTTTTTCTTACAATTTTTTGAAACTCGATG >YDL126C Chr 4 reverse complement (SEQ ID NO: 53) AGAACATTATGAAGTAAAAGGACAATCAGCACGCCTTCCAGACTTT TAAGAAACATTGATGGAGCCATTGATATCGGCACCGTACCTAACAA CAACAAAAATGTCTGCTCCTGCTACGCTTGATGCTGCCTGTATTTT TTGCAAGATTATTAAAAGTATGTCACATTACTAATAAAGAGCTTAC ACTCACACCAATGATGGCGATAGTCTCTATGTAGTACATATACATA AAGCAGAATACTAACAATCGATCCGCTATGCAACAGGCGAAATTCC ATCCTTCAAATTGATTGAAACAAAGTACTCGTATGCTTTCTTGGAC ATCCAACCTACTGCTGAAGGTCATGCTTTAATCATTCCTAAGTACC ATGGTGCGAAGTTGCATGACATCCCGGACGAATTCCTTACCGATGC TATGCCGATTGCCAAGAGACTGGCCAAGGCAATGAAGTTGGACACT TATAATGTGTTGCAGAATAATGGTAAAATTGCGCATCAAGAAGTCG ACCACGTCCACTTCCATTTGATTCCTAAGAGAGATGAGAAAAGTGG TTTGATTGTAGGGTGGCCAGCCCAAGAAACGGACTTCGATAAGTTG GGCAAGCTACACAAGGAATTGCTTGCCAAACTAGAAGGCTCCGATT AGAGTAATGCATGCTATGATTTCTTTTAGCGTTTTCTTTTCATATT TAAGTTTATACATATGGGTGTGTTTGCTTCCATTCATATCCACTCT ATAATGCTAACAATCATGTTACTAGCCATCGTTGCTATCGATACCT TATGAACAGCTCTAACTCCTTCCTTTTTAACCTACCGCCTTTTGCG CACTACCCGGCAACCCCTCGAATGTGAATTCGGTGGCAAAAAAGGA CATATATCAGGGCCGTGTATTTAAGAGATCCGCAGTTGATGTAGTC AATTAATCTAGTTCTATTAAGATTTGACTCAACGCCATTGACTCGA TAACTGGCTCAACTACAAGACAGATATACAAATCATG >YBR106W Chr 2 (SEQ ID NO: 54) CGAACTATAGGGAGATTGGTCCTCAACAATATATTTCTTCCTTGTC GACCCATTAGGTGTATGGGCGAGTTGCTGCAGGGAAGACAACGAAT CCCTAGAAGCGCACTTGTAAAGATCTTGCTCTTGTAAGTAGCGATG ACGGTCATGAAGATGAAAGGGTGCGGTTGAAGTCAAGTTGAACGTG ATCGGATACTGATTTCTAGAAACAGGGGGGGCTGGTGTTGGTTCTG GCGAAGCCGCTTGCTCCGACTGCTTTGATGTCACAGCTTTGGGTTT CTCCGCTACACTGTCTACCTTAGGATTATTGATCATGACTCAAGCT TGCGATATGTGTTGGTGTCATGCACAAGACGCCACAAATGATAGAA CAGAAAAGAAAGTGAACTAATCTTCCAAGACGAAGAAAACCAAAAT CCGGGATGAGTTGAAAGTCAAAAAGACTGTATATATAAATTTCAAC TTTTGTAGAAGATGCAGAAAAAGAAAATGATATGGTATGCAGAAAA AGAAATAAACCGCTATTATCCTCGCGGTTTGTCATTATAACAGGCA ATTACACTAGAGAAAGCCGCACACCTCCCTCCGTTTCTTTTGCCCT GCGAGTTTTTCCGGAAAAGAAAAAAAAAACGAAAATTAAAACCCGC CTGCCCCGCGGGGTGGGGGAGGGGTCACCGGAACAAATCGGATAAT CCCTCGCCTGCCTTAGATATCGTTCTGAACGGCTGAAATTATGAAA GAAGAAGAACATCACTTTACACGGATCGCACGCCCATAATTCTTTT TTTTTTTTTTTTCATATCTTCGACGTTTGCCACTGCCTTCTCTTTT TCTTTCTTTTTTGGCGGCCGGTGGCCAAACGCGCCAAAACCGAAAC GCTTATAAAATGTAGTTGCCTTGCTCTTTCATTCGATATACATATA AGAACGCTCACTGTTATCTTACATTAGAAGCTAGAAACTATAACAG TATAACACAGCACAAGAGAACCGAGCAGCCCGCCATG >YLL043W Chr 12 (SEQ ID NO: 55) AGTAAAAAGAATAGTAATTATTACAATGGAGAAGATAAGATAAAGT TAGCGGCAACAAATAAAGAACTCATCAGAGTTCTTGGCTTCTCTAT GAGTGAAAGTGTTTCAAAGGTGTTTTTTTATGAGACAACAGTAATT CCCCTCCTTCAGAACAGAGTGTAGTGATTGGCAGTGAAGCTATCCC TCTTTGCCACCCAATTTTGACGGCAGTTCTCATAGCATCTCAAAGC AATAGCAGTGCAAAAGTACATAACCGTAGGAAGGTACGCGGTAGGT ATTTGAGTTCGTTGGTGGTTATCCTCCGCAAGGCGCTTCGGCGGTT ATTTGTTGATAGTCGAAGAACACCAAAAAAAATGCTGTTATTGCTT TCTCCGTAAACAATAAAACCCGGTAGCGGGATAACGCGGCTGATGC TTTTATTTAGGAAGGAATACTTACATTATCATGAGAACATTGTCAA GGGCATTCTGATACGGGCCTTCCATCGCAAGAAAAAGGCAGCAACG GACTGAGGGACGGAGAGAGTTACGGCATAAGAAGTAGTAGGAGAGC AGAGTGTCATAAAGTTATATTATTCTCGTCCTAAAGTCAATTAGTT CTGTTGCGCTTGACAATATATGTCGTGTAATACCGTCCCTTAGCAG AAGAAAGAAAGACGGATCCATATATGTTAAAATGCTTCAGAGATGT TTCTTTAATGTGCCGTCCAACAAAGGTATCTTCTGTAGCTTCCTCT ATTTTCGATCAGATCTCATAGTGAGAAGGCGCAATTCAGTAGTTAA AAGCGGGGAACAGTGTGAATCCGGAGACGGCAAGATTGCCCGGCCC TTTTTGCGGAAAAGATAAAACAAGATATATTGCACTTTTTCCACCA AGAAAAACAGGAAGTGGATTAAAAAATCAACAAAGTATAACGCCTA TTGTCCCAATAAGCGTCGGTTGTTCTTCTTTATTATTTTACCAAGT ACGCTCGAGGGTACATTCTAATGCATTAAAAGACATG >YPR108W Chr 16 (SEQ ID NO: 56) ATAATTGCGTTTAAACGCCTTTCCTTTTCTTCATCCATTTTCCTGG TATTTATCTCATCGTCTCTCTTAATTCTTAATTTACTACCTTCATC TGGGATTATGAACTGTGGATGTTCCATATCACATTCATCCTTCCCT AAAGGACAAAATCCGGTCATGTATCTTTGACAGAAAACCTTCTTAA TATGCCGTCTAGGACAAGAACTCCCCAGAGGACAGAATCCCATTTC GTAATTTTCACATTTTGGTATCTTGCTAGCGGGATCTATGTGTAGA TATTGACAATCTGGACTTTGTGTACAGTACCCGTTTTTGCTGAAGA AGACACATTCAGGCATTTTTCGAAGATTGTATTCATGTAAGTATTC ACATTGGTCATTCTTTTTGCACAACCCTCGAAGCCAATGTCTACAA ACAATTTTATTCTGAAATATTGGTAACACATGCTTTTTTGGACATA ACGGTCCCCTCGGACATGATTTAGGGCCTTCTCTAGAATTGTAAAA TTCACAAATAGGTCTGTCAGGATCGAGTGAAAACGAATACTCTTGC CTGAGGAAAGGTTCAAATTTAAAAGGATATTTTGCTGTATCGGGGT GAATTAGGCTCATTACATAAACTTATTGATTTTATTCGTCCTAGAA TACTTGTTTAAGATACAGTGCAGAAATCTTTAGCTTATAATTCAGA AATGTGATATTTTGAAGCGATTGGAACAACAAAGTACAGTGCATTC TATATAATTATTAAAAGTTATAGTGGACTATTGTAATAACACTTGT TTTCCCCATATCATAACCGACGGCGCGTAAATGCATGCTCAATCAA GTTTCCGAATAAGTTAAGTTTGCCACCCATTGAGGATTAATATACA CAAGGCAGCATTGAAAAACCTAATTGTTAACACTACACAAATCTCT ATTGTTGTAGTAAACTGCGCTTTTTACCACTGTTACAATAGTTACT AATACACGCAAAAATTCTGGATAAACACGGCAAAATG >YIL041W Chr 9 (SEQ ID NO: 57) GCACGTGAATGTGATGTCTTGTGATGGCGGGTGAATTAGGACCGGG GTCCGCTGAGTGTTGAACTTCACAAAGCATATATCATTGACATAAT CAGAAACGTGCTTGATCAATTGTGCTATGGGGAGGTCCCGGTGCAA GATTCCAATCATCCTTTTGTTCGTGTCACCTTTGTTCTGTGCCATC AACGACAAATAGTGCGTCACAAGCAGCTTCATCGTGATTCTCTCCT TCAGGTGGAAGTTCAAGAACTGCGAAATTTGAAACTTTGGGTAACA CGATTGGATTTCCTGAAGACCTTTTGCCAATACCACAATGGCGTCC TCGTGGTCGTCCAGCAGTTCTGTGAACTTGGCCTGTATCTTGGGAG GATTGTGCAACTCGTACGGGTATGCGATTGATAGCAACGTTTGCAA GCTTTTCAAATACAAAGAGTTGGTTCTCTCAATATGAGGGTTGATT ACCGCATTATACGGTAGCCTCTGAATGGCATTAAGCCGTTTACACG TCAATGAAAGCAACAGGTTGATTGTCTTGATCGTCAGCATGTACTC CTCCTTCTTGGTCAGCGGCGGCCTGTATTGCAGGAAATACTCGTAG TTTAGGGGCGCAATTGGTTTACTAGCGTAGTCCTGTATCAGCAGCT CAATGTTCGACCTAATCTTGTAATGCTGGTCGAACGACAGTTGCGA CAGCAGCTCGTGTGAGGGTCGCTGGCGATGTGCCCAGCGCATTCCC CCACATTTCCATGAACGCATAATCTTCCACATACTACCGTGAAGGC GTCTTGATACCACGTCTTCCAGTTATGGTCTTGACTCACCAATGTT CTCAGTTTAATGTTGTTTGCTTCATACTGGCAGACATTTTCCCTTA TTACCGTGAGAAGCGAGCGGTGGATTAATCGGGATGTCAAAAACAA GAAAATTGCAACCTTCTTCACCTATAACCTATATGATTTGTAGGCA GAGGAGTGGAATAAGCAACAAATCATAGTCATCAATG >YJL166W Chr 10 (SEQ ID NO: 58) AAATCTCACTTCAGAAACGAAAAATACTACATAGATATCACCGAAT TGTTCCATGAGGTCACCTTCCAAACCGAATTGGGCCAATTGATGGA CTTAATCACTGCACCTGAAGACAAAGTCGACTTGAGTAAGTTCTCC CTAAAGAAGCACTCCTTCATAGTTACTTTCAAGACTGCTTACTATT CTTTCTACTTGCCTGTCGCATTGGCCATGTACGTTGCCGGTATCAC GGATGAAAAGGATTTGAAACAAGCCAGAGATGTCTTGATTCCATTG GGTGAATACTTCCAAATTCAAGATGACTACTTAGACTGCTTCGGTA CCCCAGAACAGATCGGTAAGATCGGTACAGATATCCAAGATAACAA ATGTTCTTGGGTAATCAACAAGGCATTGGAACTTGCTTCCGCAGAA CAAAGAAAGACTTTAGACGAAAATTACGGTAAGAAGGACTCAGTCG CAGAAGCCAAATGCAAAAAGATTTTCAATGACTTGAAAATTGAACA GCTATACCACGAATATGAAGAGTCTATTGCCAAGGATTTGAAGGCC AAAATTTCTCAGGTCGATGAGTCTCGTGGCTTCAAAGCTGATGTCT TAACTGCGTTCTTGAACAAAGTTTACAAGAGAAGCAAATAGAACTA ACGCTAATCGATAAAACATTAGATTTCAAACTAGATAAGGACCATG TATAAGAACTATATACTTCCAATATAATATAGTATAAGCTTTAAGA TAGTATCTCTCGATCTACCGTTCCACGTGACTAGTCCAAGGATTTT TTTTAAGCCAATGAAAATGAAGAAATGCGTGATCGGAAATTACGGG TAGTACGAGAAGGAAACTTGAGCCACCCCCCAAATTTTATTCATAT AATAATAGGAAAAGCAACGACCTCATCTCTCGAACATTGTTTACTT GAGCAAGTCCGATTAAGAGTAAGTTGTCGTACGTTAAATACAAATA ATCAACAAAACACTACACAAAAACTTCTACGATAATG >YDR165W Chr 4 (SEQ ID NO: 59) AAAAAACTGAAATATAGGGTTTGTTAATCCTGGTAAAAATCTGATG TGACATCTTCTGTACTTAGGTGGTCTTACCATGAAGTCAGCATCGA TACAATTGATGTTATATTTCGTTGGTTCCAATATGTAAATTGCCTC GATGGAGGATTGTCCTTTTCTTGTTGGGGAATCAATCAAATCAACA GATGTGACATTATTTAAAAGTTCTTGGGGTGTGAGGAAAAGATAAC TCAATATTGTCTCCACAGTTTTATCGATAATAAGAAACTTCAAGTT ATTTTTCGTCTCAATCTGATTCAAAACCCCTATCAAATAGTTCCTC TGTAATTCAATTAAATCAGACATCGTTCCGCCAAACCAAGCATGTG CACACTCTTCTACTTTGTCAGTGGATTCTAATTATTTTCAAGGTCT TACAAAGCAATGTCTTACTAGTTTCAATAGGGACTTAAACTGATCG TTTAAGCAAAAGAAAAACACCGTGCTGTGTGACCATCTACCAATAA TTGCGAGAACATAAGACGACGCCGCCATTCACCTCTCTATCACTTA CACCATGTTATAGGGATAAGTGTGTAGTCGATCGGCTATTCGATGA TTTTTAAAGAGTGCCTGTAATAATAGCTGTATCGCAAGTAAGGAAT ACAAGATTACTGATATTTTGATCCAGGAGGATGGACATGTTAGATA GAAAAACTAAGAGGGCTACTACATCCGGTTTAGTATTCTGTTATTG GGAATGCTTTTCCCAAGACGCAAGCAAGAGGTGACACATAAACATA GTTTTCTTATTGTATCGTTACATATTCTTATTTTACGCTGCTGTCA TTAAATATGGCACTTATCTCAGATACATTTCTTTTAATCAGCGAAA AAAATGGCGAGGTGAAAAAAATCGATGAGATGAAAAAATTTTTTAC TAGTAAAGGCGTATTGATGATATATTAGCAGCTAAAGTATAGCAAG GTTTGTCAATTTGAAGCAGTCCGCGTGTTTTACAATG >YLR330W Chr 12 (SEQ ID NO: 60) CTAACTATAATAACTGGTAGCTTTGTCACTCGTACCAGGAAAAGTG AAGATTAAACTGAATTTTAAAATGAACGATCGATTAGTTACGGAAG AGCAAGAGTTGTTTACAAAATTGCGCGAGATTGTAGGTTCAAGTAT TCGCTTTTGGGAGGAACAACTGTTTTATCAAGTTCAAGATGTAAGC ACCATAGAAAACCACGTCATTCTCAGTTTAAAATGTACAATTTTAA CGGATGCTCAGATAAGTACGTTCATAAGCAAACCCAGAGAGCTTCA TACGCATGCCAAAGGATATCCTGAAATCTATTACCTTTCCGAGTTA TCAACAACTGTCAATTTTTTTTCTAAAGAGGGAAACTATGTCGAAA TAAGCCAGGTTATTCCTCATTTTAATGAATATTTTTCCTCTTTAAT AGTGTCTCAATTGGAATTTGAATACCCGATGGTCTTCTCCATGATT TCAAGGCTCCGATTGAAGTGGCAACAAAGTTCGCTCGCTCCGATAT CCTACGCCCTAACGAGCAATTCAGTACTTCTTCCAATAATGCTTAA CATGATTGCCCAAGACAAATCTTCAACAACCGCGTATCAAATTCTG TGTCGAAGAAGAGGTCCTCCAATTCAGAATTTTCAAATTTTTTCCT TACCGGCTGTAACGTACAATAAGTAGCATGCATAAAATATAATTTA ATCAAATACTTTTGGGCAATTAAAATTTTAGTTAACAATAGTTATG CAATGCGCTTTATGTTCATATGATACCGTTTATAAGCTATTGCCAT ATCCTTATCTTATTGCTTCCAGTAGCCTCGAGTCGACCACTAAAAA GATGTCACTTAAGACGGAAATTATGTAGCTGCACTTCTTTTTTAAC AAGTTCGGTCGGCCCTTCAAGTTCTCCTTTCTAAAGCCTCATTATT TATTGCGTAGATGCTAAATGTTATCGCGGTTTAGCTTGCATGTTAC GTTTCCGTTTTAGAACCTGGTCGAGTAGCGAATAATG >YDL058W Chr 4 (SEQ ID NO: 61) TTCGCCAACCATCATACCCGAATGTTTCATTAGCGAACTGAATGAG AGCATGCCCTGGTATCAGCTTAGATAAGTTGTGCTTCCCATATTTA TTATTGTGGTAAATATTGTACGTGTACCTTTCGATCTTGGACTGTA GAAGCCCAATCCTCTGCACCGACCAAGCGCTGGCAGGTCTTCCATT CCAATCTTCGATGATTTGGAACTCTTTTATATCCAAGCCCGGTGCT GTGCCGTATGTAGTCGAATCATACGATATGCTCGAACTGGGCTTCG CTTGTATCGTCATTATTTTGTCTGTTTATCCTGAAATATGCTCTTC TCCTCTACGTAACCCTTTAATGGTCCAAAGCATGTGCTAAACTGCC ACAGACTCCCTCAATGATGTTCTTATCCTTCCTTGCCGTTACTGCT TCCTATCATATCTGCCCTTGCCAAACTGTGGCTTCCTCTAATCAAT TTGCCCCAGTACATTGAAAAGCACGTGACGTGACACCAACTTGAAA GACATTAGTGTCCAACGCGATATAATGGTCAATAAAATACCCAATT TTATCAAGTGAACATGATATTATTCAATACTATAGTACTTTAAAGA AAACTTCAACAAGTTGCTTCATTGCTATATTATACAATTATGGGTG ATGCCGGTCGGCTAACCTTTCTTTCGCAGCGCCACATACAAGAACA TATGGTAATTACTAAGAACTTTTTGGAAACTATTTCCATGAAGAAA ACAAAATTTACTGGCTTCTGTCTTCGAAGTAAATTTAGCGAACTTG ATACTTTCGTTTGGACAGTCGTTTAGATTTGCAACTGTCTGTTCTT ATTTCTTGCTATTATTACCAGAAATAAAGCCTAAAGCGCGTGGTTC TTACGAAAAAAATAGACCTTGCACATTAACAGGGTTTAGACATCAC AGAGACTGAATACTGGAGAGAAGACAATTCTTGTTCACGACTTCGA GTGATTAATATCTATAACAACCCTCCTATCAAGAATG

>YHR012W Chr 8 (SEQ ID NO: 62) TGAAAGGCAAATTTACGCTCTTCAAGACACCAATTTAGGATTGGTG GCTACCGCGGAGATACCTTTGGCAGGTCTAGGGGCAAACAAAGTTC TAGAGTTAAACTCGGGAGAATGTTCTAAGAAACTAGTTGGAGTAAG TAGATGTTACAGAGCTGAGGCAGGTGCCAGGGGAAAAGATACGAAA GGTCTCTATCGCGTTCATGAGTTTACTAAAGTAGAATTATTTTGCT GGAGCAAGCCAGAAACCAGTGCAAAGGTCCTTGAGGAAATAAAGCA ATTTCAGATTTCTGTAGTTGAGGAATTAGGAATACCGGCCAAAGTA CTAAATATGCCATCAAACGATCTTGGTAATCCCGCTTTCAAGAAAT ACGACATCGAAGCTTGGATGCCAGGAAGGGGGAAATTTGGCGAGAT AAGTAGTGCCTCCAATTGTACCGATTTCCAAAGTAGAAGATTAAAT ACAAAGTACAGGGACGATAACACAGGAAAGCTAGAATATGTGCACA CGCTGAATGGCACAGCAATGGCTATCCCAAGAGTGATAGTAGCACT AGTAGAAAATTTCTATGACCCAAGCACCGGTAAGATATCTGTTCCT GAATGTTTGAGGGAGTTTATGAATGGCCAACGATACATTTAATAAG TAAGAAAATCTTGTAAATATGTAATCTTATGTTAACCGTAGCATCA TTGTGTTGGACGAAATCCTCTGTGATGTTCTGTGTGATTGAAATTG TATGGTATTTTCGATCATACGAGTATTTTTCCTAAAGATGAAAGAG AACTCGATTCCTAAACAGTTGTTTGTAGGGCATAACGTTGTATCGT AAATACTTACCATACGCTTAGGTATATTCCTTTAGATTTCCGTAAC ACCTTTCAGTTTTACTATTCCGCGTGGCGAGGTAAAGATCATAAAA ATACAAGTTTGTTATAGCATTTCCTGCAAATAATTGCTGTAACTAG TGGCGAAAAGGTCATAGAATTATTCGCCTAAATTATG >YKL053W Chr 11 (SEQ ID NO: 63) CCGGAAGTAATTTTATCAATTATAGTTTCCAAATCATCATATTCTT GAACTATATCAATTAAATCATCACTCGTCCAGTCAGGGAACAATTC TGTAAGCGTATCTATTTTGGACTTTAGCGCAGGATTTAGTTTTTTA CTACTATGACTATTATGATTAGACTTCCTAAATTGTGTAGACATTA TATATATATGATGATGTAGATTATATTGAGAAAACGACCAAACAAA AATAAATATGTAAGTACTTTATGATGGTGATTTTTTTGGGGTAATT GGTAAGAGTTTTTCTTGTAGCTTCAAAAGATCAAATATAAAATACG AATGTTTCTGAAATTACTGTAAAAGACTTAGGAAAAGGAATGAAAC GTTTATATGGGAGAGAACGAAAATTTTTCCTTTTCCCGCCACTACT TTTTGCCACCATTTCCCGTTATTTATTTGGGCGAGTGCTCACCTCC GACGGAATCACGGGTGACGGATATCCTAAAAAGGTAAAGAATTGAA ACAGATCTATTAATATACGGATCACTATACATTATTATAAGTCGAT ATTGCAGTATTAGTATTTACATGTTGAATAATGCACATTCTGTGCT AAAATATATACTTCATTTGTCAACTTCTTTTAGTTTGCCGCCATTT TCAAACGGCGCCTCCTCCCTAGCTTCGTCTAGAGCAGGCTTAATAC CTTGTTTGACGAGAGCTGCGTTGACACATGTAGTATAAGCGTACCA TTGTTTTGAGCACTCGTTCTCAACGGATTTTCCCTTCAGGAATTTT TCGCTATACCATTCATTAAAACAACTATCGTATTTCGTCTTCAGGT CAGTGCATTCAGGCGCAAAACTAGCTGACATTATATTCCCCATATA AAACTGGTATTATTGTTATTGTAATTCAAGTTAAAACACAAACAGA TGTTTTCTAATGACCTCTCCCGGCATATATCTGGCGCACTTAGAAT AAATTTCTACATGCAAATACTCTGAATATTCTGAATG >YKL196C Chr 11 reverse complement (SEQ ID NO: 64) TTCTTCTTCTCCATTATTATCTTCAGTAGTTGTCTTGTCATCAGAT TGTCCCTGTTGCGATTTTTCATCATCTGAATGTTCTGGATCTTTTT TTTCAGAAGATCCAGCATTGTTGTCTAGTGTTTTGTCACTAGTATT TTCTTCCGAGTTCTCAGAACTTATGTTTTCATCCTTTTGATTGTTA GCGGTGGCATTGTCTTCATTGGATTGCTCATCATCTTTGGTTGATA CCTTTGATTCATCAGTATCTTTATCTTCGGAAGACTTGTTGTCTTC TTCTGCTAGAACAACCAATTCACCATCTTCAGCTACTTTTGAAGCA CCAATTTTATCACCCCCTAATTGAGGGCCAGCTTCAGTTTCATCGT TTTTGCTGTCGTTGTCATCTCCATTTTCATCGCTTTTGCTGTTGTT GTCATCTTCATTTTCTGGTGATTGCTCACCACCACTGGAAAGCTCT TCCTCTGCGGTTTTATCGGATTCTACCTTCCTTGAGGCGAAAAGAG GCTTCCTATTAGGAGCAATAAAATATAAAGCACCAGCCATAGAAAG AATCCCCATTATAAAGCCCGCTGTTTTTTCCTGATTGGAGTTCCTA CCGAACTGAGGGGAGGACGCCATGAGACGTCTTGTTTGGTGTCGGC ATAACCCCCTTGCCACTTGAATTGACGGCCTGTTTCTGCACGCATT CCTGACGACTAAGTTGCGAAGCATTTTACTGATAATATACACTCTT TGGATCGAGCCTACTTCCAGTTGGTAATTGGTGTTCCACAATTTCA GCATTATATGTTTTTAAACCAAAATTCGGCTCCTTTTCCCTTTTTT TCTTATTGGGTGGCGTGCCGTACAGAACGATTGGCTTGGTGTGAAA TCAAGAGCAAGCACAATAGATATCAACATGAACAATATACAAAAGT CTCTGGCACAGTTTGACTGCGTTAGACCAGGCTAGGGCATTTCTGA AGCTTTACGTATCACTAGAGAAGTTATTTTGGCAATG YDL103C Chr 4 reverse complement (SEQ ID NO: 65) GAAAGATGACCTCTTTCAAACGCAGTACGCAGTTTGTTGACCATAT GCGGATAGGTGACGTATATTTTCCAGAATGGTAATTTGGTATCTCC GGAATAACCCCAGATAGACTGTTTAGATACAACTTCAATCGAATCA ATAGCGTGGTCAAATGTTTCGTTTAAATAGTGCACAAACTTGTTGA TTTGCTCCTGATCGTTAGCGTCGGAAGAATTGGGCGCTGGGACGTA AAGATAGTTCTTGAACCCTGTAACATTACAAAGTACAGAGTGTCCT TCACTAGTGACACCAAAAAACCTTACCACGGTAGATGTATTTTCAT CTTTGATACCATTCAGTACGCTCTGTTCCGCATCAATTTGTTGGAA AGAAATATCATACAAACTTGGGTCAAAATCGGTTGGAAGTTTCTTA CGCTCGAATGATGACAGGTCATGCTCTTCTTGGTCGGCCATATCAT GTTCCATTTGCGATACGTCTTGTTCAAAAGTAGACTCTAATTGCGT ACCCATTAAATCTGTATCCTTTGCTTTGAAGCCTTGACTATTATAT TTTCGAAAAGAATCACTCGGAATAATCTCTATTGTTGAAACAGGTT CACTTCCAACACCATGATCTATTGATTGCCGTTTGATTTTCTTTTC CAACTGGGGAGTATCCTCGTCATCGATCTTCACATCAACCATGGGA AGGGATCTTTTTTCACTCATTGCTGTGCGTATATGTATAAAGATTA ATGCTTAATAGCAAGTGCTCAATATCTATTTTCCTTTATCCTTGAA AATTGCCTTAGATCAGTAGTACTGAGTGTTTGTTCTTCATAAGCGA ATAGCAGATGTCCTCATTGAACATTTTATAGAATAAAAAGTTACGC GTAATACGAAAAATTGCCTATTACGTTAAGGCATACTTTTACCACA CAAAACCAAGATCAACCGTCAAGCAAGAACGCTGCAAAGAAACGCA GATATAAAGGAGAACACCAGATCGAACTGCAACTATG >YLR427W Chr 12 (SEQ ID NO: 66) TCTTGAATGTCGACATATGCCCATCATCAGTGAGGAATACTCGCGT GAAGGATCTCATCTGCGACCTGAGTGATGATGAAGAAGTTGCAGCA CTACTGAATTTGTTGAAAAGAAAGTATAAAAATGAAATCCGATTGA TTGTGAACAATGCTGGAGTAAGGGCCAACTTCACCGGATTCAACGG CATGGAACGGGATAATCTTGATAAGATTTTTAAGATAAACACATTT GCACCACTTCAGTTCATTCAAGAACTGGCCCCTAGTAGACACTCAA CTAGACAGTGTTATATTGTCAATATCGCAAGCATTTTGGGCATATT GACGCCGGCCAAAGTAGCAGCTTATGCGGCGAGCAAAGCAGCATTG ATAGCCTTTCATCAGTCGTACAGTTTTGAATTGCAAAACGAAGGCG TAAGAAATATCAGAACACTATTAGTGACCCCAGGGCAACTGAATAC GGAAATGTTTGCAGGATTCAAGCCTCCTCGCCAGTTCTTTGCCCCT GTAATAGACATTACTACTCTAGCTGCCAAGATAGTCCGTTATTGTG AGCTGGGTCAGAGGGGACAGCTAAATGAACCCTTTTATTGTAGTTT TGCTCATCTTTTGATGTGCGTACCTTATTCGCTACAACGCATTGTA AGAAGCTTCTCTCGCATAGATTGCTGCCTCCCGGACGAGTAGAAAG CTATACATAGTAAATAGAATATTTATAGATGAATCCGAGTAGACAG CCTTGGTGTTTGCTTATACATTCTTTGCAATTATGCACGCCCTCAT TACCGTTGCTCATATTTTTGGGCATTAATTGTATTTTGAAAAGTGC TCGTTCAGGCCCGTGTAAAAAAAGGTGATGAAGCAAACATTATAAT AAACACTTCTGAGAAGCCACGTGTAGAGGGGTAAGCTATATCGTAA ACACCGTTGGATGTGGACCACGGTGCACTGATAAAATAAAGATATA GTAGTAGAATCTGTTACTAATCTTAACACTTTTGATG >YLL020C Chr 12 reverse complement (SEQ ID NO: 67) GCTGTAGATAGATATAGAGAAGCCGCCAAAACAGAACTAAGAATTC TACAGACTATCCTGAATAATGACCCTCAAGGTCAGTTCCAGTGCCT CTTGCTAAGGGAGTGCTTCGATTACAAAAATCACATTTGTTTGGTG ACAGATCTATACGGCAGGTCCATTTACGATTTTATGTGCTCCAACG GCATTGCCAGGTTCCCCGGCTCTCATATTCAGGCCATTGCCAGACA GCTAATCAGATCTGTCTGCTTCTTGCACGATTTGGGCATAATACAC ACGGATTTGAAACCAGAAAATATCCTGATTTGTGACGAAACCCATA TTGCTCAAAAATTGCCTTTGAAAACCGTACAGTCGCTAAGCAAGAG ACGCCGTGAAGCCAGTAAGGGGAAGCGCAAAATCTTGAAAAATCCA GAAATCAAAATCATTGATTTCGGTAGCGCAATTTTCCATTACGAAT ATCATCCTCCTGTAATATCCACTCGTCACTATAGAGCCCCGGAAAT TGTCCTTGGCTTGGGCTGGTCGTTCCCCTGCGACATTTGGTCCATC GCGTGTGTCCTAGTAGAACTGGTTATTGGCGAATCTCTTTACCCCA TTCATGAAAATCTAGAACATATGGCTATGATGCAACGAATCAATGG AACCCCTTTCCCCACAGACATTATTGATAAGATGTTTTACAAATCT AAACATAAATTGGGCAACTCTCCATCAGACCTAAATTCAACGGTGA TAAAGCATTTCGACAGAAAAACTTTAAGCTTACAATGGCCTGAAAA AAATAAACGCGGAGATACCATAACCACCGAAAAGTCAATGAAAAGG GTCTTGCAGTCATGTGATCGCTTAGATATTTACATCTCAAAGGTCT TGAAACAGGATTACGGCGATAGCTTAAGCATCAATTGGAATCTACC GCCGGAGAAAAACTGGTCTTTGATAAATTCGAAATTGGCATGGAAA AGACAAACACATTCCTCTTCTTCCTCAACTACTGATG

Example 2

Ratiometric Screening Assay (Luciferase and .beta.-Galactosidase)

[0105] In this example, the ability of a substance to modulate the chromatin modeling function of the YCR052W gene is determined using a ratiometric assay.

[0106] S. cerevisiae strain W3031a cells are transformed with a plasmid comprising a hybrid which includes the responsive promoter YOR387C (SEQ ID NO: 1) operably linked to the E. coli lacZ gene along with a plasmid comprising a hybrid which includes the baseline promoter of YHR082C (SEQ ID NOs: 52) operably linked to the Photinus pyralis luciferase gene lacking the peroxisomal targeting sequence (see Leskinen et al., Yeast 20:1109-1113 (2003)). The cells are grown, in microtiter dish wells containing 100 .mu.l culture, while shaking at 30.degree. C., to exponential phase and the culture is split in two. One culture is contacted with a substance to be tested for the ability to modulate chromatin modeling and the other culture is not. The cells in each culture are further incubated for another 2 hours.

[0107] 100 .mu.l of 1 mM D-luciferin in 0.1M M Na-citrate (pH 5.0) are pipetted into each well. The plate is shaken briefly and then the luminescence is measured wuing a Victor mulitlabel counter in luminescence mode (Perkin-Elmer Wallac; Turku, Finland) using a one second counting time. After the measurement of the luminescence, CPRG (chlorophenol red .beta.-D-galactopyranoside) .beta.-galactosidase test buffer (for example, 50 or 150 mg/ml of CPRG in HBSS (Hank's balanced salt solution)) is added. Then, the expression of the lacZ reporter gene is measured by measuring the chlorophenol red reaction product, optical absorption at 540 to 580 nm, after another 2 minutes to 24 hours of incubation.

[0108] The levels of expression, in each culture tested, of the lacZ gene is normalized to the level of expression of the luciferase gene. The normalized level of lacZ expression in the presence of the substance being tested is then compared to the normalized level of expression of the lacZ gene in the absence of the substance. If the ratio is above or below 1, this indicates that the test substance is modulating the chromatin modeling activity of the cell.

Example 3

IC90/MIC Calculation

[0109] In this example, a baseline promoter of the invention (SEQ ID NO: 53) was used to determine the IC90 of various known anti-fungal compounds. The IC90 value determined was then compared to a visually determined MIC value.

Setting up the Plates:

[0110] 1. Picked a single colony of yeast Y229-1 (P.sub.CDC48 (SEQ ID NO: 53)-PHO5-Renilla Luciferase) and inoculated 10 mL YPD (1% yeast extract, 2% peptone, 2% dextrose) containing 100 .mu.g/mL G418 (Geneticin, GIBCO, Invitrogen Corp.). [0111] 2. Incubated the cells overnight at 30.degree. C. with shaking (250 rpm). [0112] 3. Measured optical density of the culture at 600 nm (OD.sub.600) and diluted an aliquot to OD.sub.600=0.1 in YPD. Made an additional 1:100 dilution of the 0.1 OD.sub.600 culture in YPD. [0113] 4. Transferred 12.5 .mu.L of serially diluted compound or no drug control in 2% DMSO to one well of a black/clear bottom sterile 384 well plate. Covered with a sterile lid. [0114] 5. Added a 12.5 .mu.L aliquot of diluted Y229-1 cells to each well of the 384 well plate. Final DMSO concentration was 1%. [0115] 6. Covered the 384 well plate with a sterile lid, placed in a plastic bag to limit evaporation, and incubated for 24 hours at 30.degree. C.

Preparing the Luciferase Assay:

[0116] A Promega Renilla Luciferase Kit was used in these steps (E2820, Promega Corp., Madison, Wis.). [0117] 1. Add 12.5 .mu.L 1.times. Lysis buffer per well. [0118] 2. Add 25 .mu.L Assay Reagent per well of 384 well plate. Read light output immediately on an appropriate device (e.g., LeadSeeker, Amersham Biosciences, Piscataway, N.J.).

TABLE-US-00006 [0118] TABLE 4 Correlation of IC90 calculated from luciferase light output and MIC determined visually 5FC AMB CSP FLU TRB VOR IC90 1.9 0.3 0.02 0.3 1.4 0.008 (.mu.g/mL) MIC 2.5 0.3 0.015 0.2 1.56 0.015 (.mu.g/mL) IC90, inhibitor concentration at which there is a 90% drop in signal relative to the uninhibited control; MIC, minimum inhibitor concentration at which there is an approximately 90% drop in cell number relative to the uninhibited control; 5FC, 5-fluorocytosine; AMB, amphotericin B; CSP, caspofungin; FLU, fluconazole; TRB, terbinafine; VOR, voriconazole.

Example 4

High Throughput Screen

[0119] In this example, a baseline promoter of the invention (SEQ ID NO: 53) is used in a high throughput screen to discover compounds with antifungal activity.

Compound Preparation

[0120] 1. Prepare compounds in 5% DMSO. [0121] 2. A control inhibitor, amphotericin B is prepared at 25 .mu.g/mL (in 5% DMSO) to produce 5 .mu.g/mL (final concentration).

Culture Inoculum Preparation

[0121] [0122] 1. Inoculate 10 mL YPDU (1% yeast extract, 2% peptone, 2% dextrose, 80 .mu.g/mL uridine) supplemented with 0.1 mg/mL G418 (from 50 mg/mL stock) with yeast strain Y229-1 (P.sub.CDC48 (SEQ ID NO: 53)-PHOS-Renilla Luciferase). [0123] 2. Grow Y229-1 overnight at 30.degree. C. with shaking (250 rpm). [0124] 3. Measure the optical density of the yeast culture at 600 nm (OD.sub.600) and determine volume of yeast culture needed for OD.sub.600=0.1 in 5 ml YPDU. [0125] 4. Further dilute this 5 mL culture 1:20 in YPDU (this volume is sufficient for approximately 5000 assay points).

High Throughput Assay Set Up

[0125] [0126] 1. Add 5 .mu.L compound or 5% DMSO to a sterile 384 well plate (e.g., Matrix Technologies, Hudson, N.H. catalog #4331). [0127] 2. Add 20 .mu.L of dilute inoculum to each well containing compound, amphotericin B or DMSO. [0128] 3. Cover plate (e.g., Matrix Technologies catalog #4320) and incubate 24 hr at 30.degree. C. [0129] 4. Prepare 1.times. Lysis Reagent from Promega Renilla luciferase kit (catalog #E2820) by diluting 5.times. stock in deionized H.sub.2O. [0130] 5. Add 12.5 .mu.l 1.times. Lysis Reagent to each well. Incubate at room temperature for 1 hour. [0131] 6. Prepare Assay Reagent as described by manufacturer. [0132] 7. Dispense 25 .mu.L Assay Reagent into each well. [0133] 8. Read immediately on an appropriate luminescence detection device.

Example 5

Ratiometric Dual Luciferase Assay

[0134] In this example, a Renilla luciferase and a firefly luciferase reporter is linked to a gene responsive and a baseline promoter, respectively, and used in a ratiometric assay to determine whether a substance inhibits fungal cell growth.

[0135] Strain construction. A double recombinant strain comprising a chromsomally integrated YOR387C promoter/Pho5-Renilla luciferase hybrid and a chromsomally integrated YHR082C promoter/Pho5-Firefly luciferase (--SLK) hybrid is constructed. The yeast strain, Y229-1, is transformed with plasmid pSPRT190 (SEQ ID NO: 87), comprising gene responsive S. cerevisiae YOR387C promoter (SEQ ID NO: 1) operably linked to Pho5-Renilla luciferase. The YOR387C promoter/Pho5-Renilla luciferase hybrid integrates into the Y229-1 cell's chromosomal TRP3 locus. The pSPRT190 plasmid comprises the KanMX gene for selection. The recombinant strain is, in turn, transformed with plasmid pSPRT50 (SEQ ID NO: 86) comprising baseline S. cerevisiae YHR082C promoter (SEQ ID NO:52) operably linked to Pho5-Firefly luciferase (-SLK). The YHR082C promoter/Pho5-Firefly luciferase (-SLK) hybrid is allowed to integrate into the Y229-1 cell's chromosomal HO locus. The pSPRT190 plasmid comprises the KanMX gene for selection

[0136] Assay. Test and control double recombinant yeast cells are mixed in growth medium and diluted to OD.sub.600 of 0.2. Two experiments are set up: (i) double recombinant strain contacted with the substance being tested for the ability to inhibit fungal cell growth and (ii) double recombinant strain contacted only with a blank. Then, 25 .mu.l of the diluted yeast strains are added to microtiter wells containing a compound to be tested for the ability to inhibit fungal cell growth or a blank (10 .mu.l compound [dissolved in 100% DMSO] per well). Yeast and compound are incubated for 3 h at RT, followed by the addition of 25 .mu.l of firefly luciferase reagent (Promega, Madison, Wis.) to each well, and incubated for 1 hour. Luminescence (firefly luciferase reporter) is determined using a Viewlux plate reader (Perkin Elmer, Wellesley, Mass.).

[0137] After reading the firefly luciferase counts, using a Victor2 plate reader (Perkin Elmer, Wellesley, Mass.) equipped with an injection system and interfaced in a Thermo-CRS stacker-based robotic system (Thermo-CRS Ltd., Burlington, Ontario, Canada), 25 .mu.l Renilla luciferase reagent (Stop & Glow, Promega, Madison, Wis.) are added to each well individually, and luminescence is determined immediately (within seconds, due to the short half-life of the Renilla luminescence).

[0138] The relative levels of expression from the YOR387C and YHR082C promoters, in the presence and absence of the substance being tested for the ability to inhibit fungal cell growth, are compared.

[0139] In this assay, the compound being tested for the ability to inhibit fungal cell growth is selected if the responsive promoter (YOR387C) expression level (Renilla luciferase) decreases or increases in relation to the expression level from the baseline promoter (YHR082C) (fire fly luciferase) when the relative expression levels in the presence of the substance being tested are compared to the relative expression levels in the absence of the substance being tested.

[0140] Alternatively, the plasmid pSPRT47 or pSPRT192 can be used to construct the assay strain. Plasmid pSPRT47 comprises a Pho5-Renilla luciferase construct to which a promoter can be operably linked, an HO targeting sequence, and the KanMX gene for selection. Plasmid pSPRT192 comprise a Pho5-Renilla luciferase construct to which a promoter can be operably linked, a TRP3 targeting sequence, and a hisG:URA3:hisG consruct for selection and counterselection (e.g., using 5-FOA).

[0141] The present invention is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims.

[0142] Patents, patent applications, publications, product descriptions, Genbank Accession Numbers and protocols are cited throughout this application, the disclosures of which are incorporated herein by reference in their entireties for all purposes.

Sequence CWU 1

1

8811006DNASaccharomyces cerevisiae 1gccagggaag cctatatctg attccctgtt tcataatcca atgcagccac tagcttataa 60ttatttgaac tatttgtcga acatcacagt aataaaatcc ccagaaagtt ccacttgctg 120catattggca cctgttgatt cactctccat cacttttttg ttagccgccc agcctagaaa 180gtctttaaat acatctgaaa tttttttttt tttaacagtg cacccgtgca tcatacctca 240tgcaaggtac ctttttttct caaaggtatt gtcttccatt gaagtggcac tatggcatga 300tgaaccctga gcatttctga attcaacaga accaaattgt ccagaaataa atctgtccga 360catgaattat gaaacttttt ttcaattaag tgaagagaat tttgcagcgt cttaccatta 420ttttgaccca ttggtcgcat gtttgcgctt tgacttcgag aaccatgtta aagcttactt 480gtacgacaac caatgaagta tattacggca gtttttttgg actgggtcaa aaaaagtgtt 540gcataatcaa atcaggaaca cattaaaatg ttgtaaaatt tgtcttagta tcacctgagt 600ggttattcat tacgtactac tgtcaaaata ttcggatctt tcctaaacgg gcttttgaat 660tagtgttgct tctattcctg gaatggaagg taatactttc atgcattctc gcttttcgga 720cttttaacaa taaattaaaa acaatgatac tttcatcaac tacctataca ccctgcgggt 780caattatttt tttttcgaat aaccgctgag gttggaaata tagaaacata ttccagatct 840gtattttcag ttgctagaaa aaggttaata taatcattaa ggttttcagc atataacagg 900tataattgat atataagcat cgtaattttc attcaaaatg gagagctact gcttctgata 960gattgtacaa tctcaagaaa tcaagaacaa caaccatacc atgagt 100621003DNASaccharomyces cerevisiae 2ttgtgtttag acttaagtat gaaaatttta tgtatgagct gtggctatgt atccgctggc 60aaataggtct gctttttcta cactttccac cctcaaccta acagagcccg ctggcacaaa 120taatcgatag taggacaaca gagctactcc ttcttatgcc ccgccccttt gagcttgttg 180tattgctctt gatagttgtg tttttcactt tcatcagcat cggtagtctt gccgtccttg 240tcttgactag ccattttctt aaaagcgtca ctcactacct ttgcatcgcc ctgcaatttt 300tcctttgagc tctgaaatat ttcgctcact ttttgttggt ctgtattcat tctggatgtc 360ttggttgtag aaatttcttt tattggttca ttaaagtcaa ggtaaatggc gagaactaga 420atagagtttt attcttttta ccgttatata gataattcta gccgggggcg gtcgcccctg 480agattcccga catcagtaag acatagtact gtacgattac tgtacgatta atctatccac 540ttcagatgtt caacaattcc ttttggcatt acgtattaat acttcatagg atcggcaccc 600tcccttaagc ctcccctaaa tgctttcggt acccctttaa gacaactatc tcttaacctt 660ctgtatttac ttgcatgtta cgttgagtct cattggaggt ttgcatcata tgtttaggtt 720tttttggaaa cgtggacggc tcatagtgat tggtaaatgg gagttacgaa taaacgtatc 780ttaaagggag cggtatgtaa aatggataga tgatcatgaa tacagtacga ggtgtaaaga 840atgatgggac tgagagggca attatcatcc ctcagaatca acatcacaaa catatataaa 900gctcccaatt ctgccccaaa gttttgtccc taggcatttt taatctttgt atctgtgctc 960tttactttag tagaaaggta tataaaaaag tatagtcaag atg 100331003DNASaccharomyces cerevisiae 3gaggtttcaa catgccaaca atggaagtgg ttaagagacg ttttctggtt tctgggcagc 60tgttacatag aatctctgat ttacatgctc aagtattcgc aaagatcggt atgatgggaa 120aataggtgaa ttttgggata atgactgaga ttataccgtt gttaatgcta taatattaat 180tatacagaat atattagaag ttctcctcga ggatatggga acccacagaa gcgaatcgat 240gtttctacat aaaagaaaaa aataatctca ttttatcttc ggttttgaat cttttcattt 300ttttttccta ttacattatc aattctggca tttcagtgtt tataaaaaga tcaaattgct 360gtttgaaact cattgcgcta attccataat tttgcaccat gtatgctcat gactccatat 420aggacaacat actggtagga atattatcaa gtgaacgata acggttcttc tcccaacaag 480aagtaagcct ggtgagtgta ttttgaagct ttttggaggg gcggccacgg aataagatat 540gaacacatac tggcaattgg gctgagatct gattacattg tcgacagatt cccatgaagg 600tgtttgagag aattttgatt gagtcgttat acaaattgct gtggacacgt acgcataaag 660tagttcgggc agctatgttt gccacgtagt agctacaata ttaagcatag cagactaaat 720gcaattggct gtgttgaaag aaacttctga actgagattc aagtaacgtg attgtgtgcg 780ccattttaca caggctgcgc ggcaaatcaa aaccaaagat acttctccgg aggtatacgt 840gttgcatttt caacagacta tacgagtttt ttctgatcgt tgtatattta agtgcagctt 900ggacttacaa gctctatact aggataatga tctcattgga ttcaagagaa agaaactcta 960tactggcgcc aaattagcag tgtcaaattt cgaaaaggtg atg 100341003DNASaccharomyces cerevisiae 4ttcttttttt tttttttttt ttctttttgg gaacggggga aaaggtctca ctagtatata 60aaggaaagag agtacagcac gaatgagcca gctgcaggaa aggggctagg ttaaaaaata 120aaaacccagc agaaagcaaa caaccaaata taatttagaa atggacagag accatattaa 180tgaccatgac catcgaatga gctattccat caacaaggac gacttgttgt taatggtttt 240ggcggttttc attcccccag tggccgtctg gaagcgtaag ggtatgttca acagggatac 300actattgaac ttacttctct tcctactgtt attcttccca gcaatcattc acgcttgcta 360cgttgtatat gaaacgagta gtgaacgttc gtacgatctt tcacgcagac atgcgactgc 420gcccgccgta gaccgtgacc tggaagctca ccctgcagag gaatctcaag cacagcctcc 480agcatatgat gaagacgatg aggccggtgc cgatgtgccc ttgatggaca acaaacaaca 540gctctcttcc ggccgtactt agtgatcgga acgagctctt tatcaccgta gttctaaata 600acacatagag taaattattg cctttttctt cgttcctttt gttcttcacg tcctttttat 660gaaatacgtg ccggtgttcc ggggttggat gcggaatcga aagtgttgaa tgtgaaatat 720gcggaggcca agtatgcgct tcggcggcta aatgcggcat gtgaaaagta ttgtctattt 780tatcttcatc cttctttccc agaatattga acttatttaa ttcacatgga gcagagaaag 840cgcacctctg cgttggcggc aatgttaatt tgagacgtat ataaattgga gctttcgtca 900cctttttttg gcttgttctg ttgtcgggtt cctaatgtta gttttatcct tgatttattc 960tgtttcattc cctttttttt ccagtgaaaa agaagtaaca atg 100351003DNASaccharomyces cerevisiae 5gaagttacaa ataataacaa caaagttaat aacagtagta gcaaccctga tatttccacc 60aactcggtag ttcataacgc aatgcaattt acaaatacaa acaacaatac aagtagcact 120gtggatataa acgatcccaa aaatattgca ccccctccta caacctctgt ttcagcccca 180agcactccaa ccttgtcctc atcaagtcaa atggcgaata tggcttcgcc tagtaccgat 240aatggtgaca atgaggagaa aaatggtggt aagaagaaga gatttggcct attcaaaaaa 300aaaaataaat caaagaaata atatccttcg acagcttaat gaacacgcat gtaaatgttt 360tgtaaacagt ttgttttttc gtttttgtat ctgttaattt tctattattt atttttttag 420tttttttttg cggtagaatt gggttatcac tgaatctatt ttattttttg ggttggtttc 480tccctgtttt cagtttgttt gaattggtgt ttaacaaaat ctggaattat tcactataat 540tatttcctct ttttagtttg accaaataaa ctcaactatc ttgtgttatt tctttgtatt 600atagctttac acatatttaa ctatccatac cttttacttt ttgtatatac tgttaatttc 660ataaaacacg ttttagtacc agaaaatcgt gtcatagcac cgttttagca gtgattttta 720aaattgtcca aggtgccaat aaatactggt gggaacaaca ttttaattag aatagctaaa 780accttctaag aaaactatcc cagcgtagaa agaaagaaat ctctatcagc cgcgcaagtg 840cagtatctct tatttttgca cggccccgtc gctatattgt cacacgcatt tgaattagtg 900actcaataat aatacagatt tgtgacgtat aaagaaacca cagaaaaact gcgtatgtcc 960gaagcacagg tccactagta atagagccca aaaatctgac atg 100361003DNASaccharomyces cerevisiae 6aggttgccac atacatggcc aagaccggta agtcagcctt ggaagcagaa aaggaattgc 60ttaacggtca atccgcccaa gggataatca catgcagaga agttcacgag tggctacaaa 120catgtgagtt gacccaagaa ttcccattat tcgaggcagt ctaccagata gtctacaaca 180acgtccgcat ggaagaccta ccggagatga ttgaagagct agacatcgat gacgaataga 240cactctcccc ccccctcccc ctctgatctt tcctgttgcc tctttttccc ccaaccaatt 300tatcattata cacaagttct acaactacta ctagtaacat tactacagtt attataattt 360tctattctct ttttctttaa gaatctatca ttaacgttaa tttctatata tacataacta 420ccattataca cgctattatc gtttacatat cacatcaccg ttaatgaaag atacgacacc 480ctgtacacta acacaattaa ataatcgcca taaccttttc tgttatctat agcccttaaa 540gctgtttctt cgagcttttt cactgcagta attctccaca tgggcccagc cactgagata 600agagcgctat gttagtcact actgacggct ctccagtcat ttatgtgatt ttttagtgac 660tcatgtcgca tttggcccgt ttttttccgc tgtcgcaacc tatttccatt aacggtgccg 720tatggaagag tcatttaaag gcaggagaga gagattactc atcttcattg gatcagattg 780atgactgcgt acggcagata gtgtaatctg agcagttgcg agacccagac tggcactgtc 840tcaatagtat attaatgggc atacattcgt actcccttgt tcttgcccac agttctctct 900ctctttactt cttgtatctt gtctccccat tgtgcagcga taaggaacat tgttctaata 960tacacggata caaaagaaat acacataatt gcataaaata atg 100371003DNASaccharomyces cerevisiae 7cttagtatac gattgtgttc ttgcccacca tctactaaca aaatatggca agattaaacc 60tagtagcgca acataacaaa ccactaataa tggagatgca cttccatcta ccaaaaatct 120tggtagagcg ataccatgtg aagtagattg tgggccatct ggatgaccgt atttcaaata 180gttttgccta accaattcgt cagtaaggga ttcgtaagcc ttcgtaatct gaacataagt 240ttcttccatc acacttttct catcaggtgt taggcccttt gctaatttat ctggatgaaa 300tttaacagat aattttctat aagcagattt gatgtctcta tcggaagcac tagtagagat 360accaaggatt tcataaggat caaataattt tgtagcagcg tctttaatcg cgtcattact 420attaatcctt tgcagaagaa ttgcaactaa gatccaaccc acaataatta taatatttct 480cctgctccat attttggact tcttattact atttttatca aacttccttc taaattgttt 540gatttcatca ctggtgtatt cttcattcaa gttcttgaaa acttcctcat taaactcctt 600actcttccct gaattcccat cttcagcatt ggccccaaaa aaaatttggt atatttgaag 660cagtgtcata ggcccgacga ccatcaagag ccccgttaaa atgaaggacg gccacgtctc 720actagcctca tcatactcgt aatttgtagg cattgtgctg taatatgcag tatatttatt 780ttgttgcgaa ggccttcttt ggtcaattat aactgactat tgttccagtc gcatctttta 840ttcgttcagt gatcttcgac gtgttcaaga caaatttttc agaaaacgcc tttccgtaac 900gagtgaccaa ttcgcgttat aagagcgatt gtgtcagtaa tgaagtcaga ttgtgacatt 960ataaagctaa gacgttaata actcaaaata gaaaagaagc atg 100381003DNASaccharomyces cerevisiae 8aaataagagg tttggccaaa acgtggtcat ccaaggttga tggattcttc tcttctaata 60ttattaataa tggatcgaaa catatttgag gcaaagctag ttcccattct tttgccaaga 120aagcggaggg agaatgatcg taaagagtca caacgtccct aggaaacagt ttttggaaca 180atttctgaaa tgtattcaaa ataggaataa tatcacttga atagctgttt tcgtgaacgg 240atgtcgtttg accgatcgaa acagaaaagg atttggcatt tgcagtcgtg aactgtttgt 300atgagccatt gtccaaccgt cttatgtcat aatcggtgaa aatgctgaaa atatttgaca 360gcgaaagatc aactgaagcc ttgatgaatg gctccaaata tataaacccg ctactttcaa 420atagtatctt tgttgtctta ttcatcatag gttttatatc tctcaatacc tgcgggattt 480cttgcagtga agacgcactc attattatca agtcgaatac caagccacca ttttcattat 540taaggtctac taaatctagg agcgattgga aatggttttg aatctgaaac cgttccgtcc 600cataaaatag tgaactaacc tcgtagttgg cattttttga gttgttcaca agataaaatt 660ctatattttt ggcatgttga aacctggatg tgtacagaat gagatttggg tgatctccgc 720ataccaaaac ccttaatgca gatgtcatta ttcaatatac ctatcgcgag atatgccggg 780aataaaatgt aggaaacaaa aagaaaaata tatgcacagt agttcaaaca gaatagaaat 840gacggagagc aaatatttgg gtagaatcac agactttagt gttggttaca agcttttcga 900atggatgtag tttgtaatca aaggacacta ataatagcga aaaaaaaaag ggcaagtatg 960ttggcagtcg cctctttttc aatttagcgg taagttttta atg 100391003DNASaccharomyces cerevisiae 9cgcaaatgat gagaaatagt catctaaatt agtggaagct gaaacgcaag gattgataat 60gtaataggat caatgaatat taacatataa aacgatgata ataatattta tagaattgtg 120tagaattgca gattcccttt tatggattcc taaatcctcg aggagaactt ctagtatatc 180tacataccta atattatagc cttaatcaca atggaatccc aacaattaca tcaaaatcca 240cattctctac attactagta tattatcata tgcggtttaa gaaaatggta taaagattaa 300gaaacagtca tgaaaattta gtgaagctga aatgccagta ttgataatac gatagaataa 360tgaatgacaa agtatataag gaagatgaag taacattatt atggagaact atcgactccc 420ttttgtgaat ttctatatcc tcaaggagaa ttgcttgtat actatgtata tataatatta 480taacccttga caacaatgga ataattagtc cttaaacgtt agactggctg ggacagcacg 540acctctgttg gctaatttta cttttcccac aaccgtagat cttgatttca tgactgtttt 600cgtggtaatg tccgaatgat acatatataa gttatatgct ttcactttat aagtattagc 660gtttttactc accatccact gctttgagaa gatgtggtca gcaaccacgc aatacatcac 720atattttggc acgggtgatg taccgatcta atggctaagc ttccttttgg aagctgatag 780agatccagat ttgcatctct atcgctattg tcgtcatcga cactgctcac ttagtgctgc 840aggtaaattc cgtttttttc caaattaata tttatgaacg ttatgatgtc aagttttttc 900aagaagtaat tatccgcgaa aaaaagaata taaaaaatac aaatgtgcat agatcctcac 960atagtataca actaaaaagc aaacaaaaga acatcctcaa atg 1003101003DNASaccharomyces cerevisiae 10caatgattct gaaatactcc ttttacaacc tttgcaaaga taatgtcttt cagtctgata 60ttacgagcga cctagaacca ctaatccata ttcttcattc aacttactcc attttccttg 120gcaaacaatg ccccacaatc atatacgtca taactataag ggatatgtct ggaatgcggc 180caagatagaa ttaaagggct gcagaacacc actactgata ctcattgcca aggctaggag 240gcaccatccg tttcattttc tttgaggtaa gccaatcatg aaatagtata cacatccata 300acggacgtac ggacgaaata agtgccgttg tcccactatt ccaccgcatt tggcccattt 360ggctcacttt gactcaactt gcgtcatttt aactgatatg aagggtccga ctttgtcctt 420tttcggccac cgcatacccc acggcgatgc ctccgctacc tgcatttgag tagcatctcc 480gtttcgcggg gtattcggcg ctacgtcgcc tgttcgagcg gctctgttcg ttgcatgaaa 540ctaaaataag cggaaagtgt ccagccatcc actacgtcag aaagaaataa tggttgtaca 600ctgtttctcg gctatatacc gtttttggtt ggttaatcct cgccaggtgc agctattgcg 660cttggctgct tcgcgatagt agtaatctga gaaagtgcag atcccggtaa gggaaacact 720tttggttcac ctttgatagg gctttcattg gggcattcgt aacaaaaagg aagtagatag 780agaaattgag aaagcttaag tgagatgttt tagcttcaat tttgtcccct tcaacgctgc 840ttggccttag agggtcagaa ttgcagttca ggagtagtca cactcatagt atataaacaa 900gccctttatt gattttgaat aattattttg tatacgtgtt ctagcataca agttagaata 960aataaaaaat agaaaaatag aacatagaaa gttttagacc atg 1003111003DNASaccharomyces cerevisiae 11cttagtatac gattgtgttc ttgcccacca tctactaaca aaatatggca agattaaacc 60tagtagcgca acataacaaa ccactaataa tggagatgca cttccatcta ccaaaaatct 120tggtagagcg ataccatgtg aagtagattg tgggccatct ggatgaccgt atttcaaata 180gttttgccta accaattcgt cagtaaggga ttcgtaagcc ttcgtaatct gaacataagt 240ttcttccatc acacttttct catcaggtgt taggcccttt gctaatttat ctggatgaaa 300tttaacagat aattttctat aagcagattt gatgtctcta tcggaagcac tagtagagat 360accaaggatt tcataaggat caaataattt tgtagcagcg tctttaatcg cgtcattact 420attaatcctt tgcagaagaa ttgcaactaa gatccaaccc acaataatta taatatttct 480cctgctccat attttggact tcttattact atttttatca aacttccttc taaattgttt 540gatttcatca ctggtgtatt cttcattcaa gttcttgaaa acttcctcat taaactcctt 600actcttccct gaattcccat cttcagcatt ggccccaaaa aaaatttggt atatttgaag 660cagtgtcata ggcccgacga ccatcaagag ccccgttaaa atgaaggacg gccacgtctc 720actagcctca tcatactcgt aatttgtagg cattgtgctg taatatgcag tatatttatt 780ttgttgcgaa ggccttcttt ggtcaattat aactgactat tgttccagtc gcatctttta 840ttcgttcagt gatcttcgac gtgttcaaga caaatttttc agaaaacgcc tttccgtaac 900gagtgaccaa ttcgcgttat aagagcgatt gtgtcagtaa tgaagtcaga ttgtgacatt 960ataaagctaa gacgttaata actcaaaata gaaaagaagc atg 1003121003DNASaccharomyces cerevisiae 12cataagaaac aaattttgta agtttcttgt gccttttgag tttgaaatca ttgaccagaa 60caatgagaac tctaaacacg acaaatggat cttaaatcaa ttttcttgaa aacatcttcc 120agtttcgata ttcgcacatt tgccggtaaa atagtgcaat ctgcctatac ctttaaaatg 180ggatcttgaa cgcgtacctg aaggtttttt taaataaggc cgaacctaaa tgttgccttc 240aaaattaacc tgtatcaaat tttgaagccg aagttggtat cctcacattg tctaacctca 300tggtctccta aagtccggcg atcactttcc gttgcgtgac tattgatgat cagactgtca 360acaatgtcgt tccgggcctc catagcttga agaattttcg ttgacggaac tagaggaatg 420gcagatggag atgaccttag tttcatgtcg ccttgatagt tatcaaagag tacagaaaca 480agacgtctct tgctcaataa taaggattgg atcaggtgct tacaaatttt attcgtcata 540caaacaatta ctaatatttt tttaatatta agcgtacccc tatttgattg gctctcttct 600aaattcatac gttttaaaat ccgctttcaa ccgtcaacat aaaattagta agcagacctc 660gttccaagac ccaactaagt tgcactaaat atcctcgaac aaattggggg cagatttttg 720aaccatataa aagtcatgac aatatttcca gatcaaggac agttgcagtt cttcctttca 780tcggccagct gacgaattga ctgagcggct ttgtatttca ctagaataca cttcctatag 840ctacaaaata ttattcaata atattagtga attatttaaa cctctacctg aaccacctac 900cgagttggga cgtctcaggg ttctttctaa aactgccggc ataagagttt caccgctaat 960tctgggagga gcttcaatcg gcgatgcatg gtcaggcttt atg 1003131003DNASaccharomyces cerevisiae 13agaacatcca aattcggaac tactaagaag atatgggtat gttgaatggg acggttcgaa 60gtatgatttt ggagaagtgt tacttgaaaa tattgtcgag gcgttaaaag agacttttga 120gacgaatact gaatttttgg acaggtgtat tgatatctta cgcaataacg ccaatattca 180agaattctta gaaggtgaag aaatagtact agattcatat gattgttata ataatggtga 240attgttgcct caactaatac ttttggtcca aatcttgaca attctttgcc aaattccagg 300tttatgcaaa ctggacataa aagcaatgga aaggcaagtg gagagaattg taaagaagtg 360tttacaattg atagaaggtg cccgcgccac tacaaactgt agtgccacat ggaaacgttg 420tattatgaag cgtctagccg attaccccat aaaaaagtgc gtttctatcg aaaaaccttc 480gaaaggaaac tcattaacaa gggaagaact aagagatgtt atggctcgga gagttttgaa 540aagcgaaata gattcgctgc aagtttgtga agaaaccatc gacaagaatt acaaggttat 600tcctgatgaa aagctgctaa ctaatatttt aaagagaaag ttgacagagg aagaaaaaag 660ctctgtcaaa cgtccttgcg tgaagaagtg agcggttgtt ctaaccacta tttaaagccg 720caattagtaa tgcaaaaagt tggccggaat tagccgcgca agttggtggg gtcccttaat 780ccgaaaaagg acggctttaa caaatataaa ctccgaaaat ccccacagtg acagaattgg 840agaaacaacc agttttgata tcgccataca tataaagaga tgtagaaagc attcttcact 900gtaatgtcca aatcgtacat ttgaatttct tgtaggttta tttaaaaggt aagttaaata 960aatataatag tacttacaaa taaatttgga accctagaag atg 1003141003DNASaccharomyces cerevisiae 14gttgaacttt attcaaatat catcgaagta agaagatata ctactaaaga ctccctttgc 60tctatattcg agtcaggctc caccagtcat ttcgaaatta accagttaca ggtcaaaaga 120ctaaacttac tgcaaaacca atttgcttct gttttcactt ctttccaccc caaagataat 180acaaagggca tacatatcaa ttttttttca cctgtcacta ggataactga ccttcaatat 240tccttttttt atacgaatca gatactgttc ggtacacgat atctaattaa aatgattcaa 300aactttgtaa caggtaaagt tttcactaga accaatcaat ccaagtgaat taggggaaac 360catagttgtt gatttgtaga aacctcacat tgtacattgt tggtttgttg ggcatatcag 420aacgagagat tttccaacat tcaatataca ctaaacccta tgacgagtcc cacagatggc 480gtaaggtttt tatgatttca gcagggtacg acgactagta ccatattaac attttttagt 540gtttctaatt tgggaaaagg tccgtgtttt ttctcctagc aaccgtttag tgccaagggt 600taggcaattg aacgaggcca agacaatatt ggctttgctt ctattacttg gctaacattg 660tgtctgcagg tcgaaaggca cctttactgt aaggaacatt cttgcgctct aaacatacga 720agatatgggg aatatgaagc gtgtttctta tacgaagtgc agcatcgttc aaggaaaata 780cacccccata gtaataatgg ctaagtggcc aggaattaga atatgtgaga tatgagtgca 840aaatgagtga ccagtaatag cctgtttggg atgtaattgc tcaaaaaatt tatataaata 900cagcggtttg atcagctttg tttgagacat ttctctgttc ttttccttcc agttaagctt 960atatctccac taagcaacaa cccaaaaaac aacaaataca atg 1003151003DNASaccharomyces cerevisiae 15cagacttgtt gtctgtgctg ttacttgcac ttgctgcatt gctatttgcg ttcaaatcac 60ctttttcgat gaggaggtcc ctttgcttct ccaccatcgc ctttgtgtaa cgcaacattg 120tccaatcgaa caagtggtcg ttgtgatact ctagtttaat actcagatct ttaaacagcc 180ttgccaagaa caaataatct ggcttctcat cgaatttcaa attcttacag taagccatat 240attcttgaaa ctctaatggt aaacctgaac atagagtttc cacgctaacg tttaatttct 300tttccatgat acgatcatac ttttgtttct

tggtggttgc tttcaaaccc tgccatggca 360aagaaccctt acaaaaatag atcaagacat aacctagtga ttctaagtca tctcttctac 420tttgctctat tccaagatgc gtattgacac ttgcataacg agctgtacct gtcaaggact 480tgttctccct gtaaggaata tgacgatgtg tgttgaaatc tcggtatttc tttgatagac 540cgaaatcaat aacatgaacg gtgctaccac ggcgtcctac ccccattaaa aagttgtctg 600gtttgatatc tctatgaatg aacgaccttc catgtatata ctgaatacgg caaaacattt 660gcaaagccag catgataacc gtcttaaagg agaaccttct gtgacagtag ttgaataaat 720cttccaaaga tgggcctaga agatcgatga ccatagcatt atattcaccc tctctgccaa 780accatctgat gaacgggatt cccacaccac cgcttaagta tctgtagacg cgggactcat 840agtccaattg aggatgtctg gacctgatcg attccagctt gatggctact tcttcaccac 900taattaagtt cgtgccgtgg taaatgtcac caaaggaacc actcccaatc ttcctgccaa 960tacgaaattt ccttcctact cttaagtcca tctcttttta atg 1003161003DNASaccharomyces cerevisiae 16tcactcaacc acctccaaaa aataacaggt tcatctaaag taaaagactt taacttgctc 60ttagtttcca aattaaatat ctgcacgata gtaccatttg ctctaacgga aataaccatc 120tgagatggat gcatgatagc agaatcaccg cccatattct tccttgtcac ttcattgcct 180ttggccaaat ccacgattgc aacagagttt gtaccgtcct ttgtttctct aacagtgacg 240aagtggtcac tctcgaaagt agttgatctg aagtcaagga attgagggga aattcctaag 300gacatcagat cgaccaattc ggtaaattca atgggtaggt cactcattgg ttagaacttt 360cgtgataatt tatttttata gttgaatatc ttctttctct ctcaactctg atccggattg 420tcgaggtttc aataagttac tctgaacaac taatcaaaat atctccttat ttctgtagat 480tccttcagtt ccacttttta cttttcttaa ttctctttgt atttattcct agcgacgaaa 540aatgcgagat ctcgaccaaa aaaagggggt agggtaataa aattaaccct attatttttt 600aactttaaaa cctataatgt gctaatattt tattataaac ctcctttttt tgcgttcaaa 660ccctgacaca ttttaagccc tatatttacg gtattagttg attaaactcc gaagcgaaag 720gaattcggtc attagcggct aatagccgtt ggggtaaatc acctacaagc aagtacacaa 780gagaacgttg gcgttgttaa gtcaaagcac taatacattg gggctttaag agtgtttata 840aaggtctaac ctgtaaaaat tatttaaaca acttgaacag gccttaaagt tttcctcatt 900ccgctcatca tcactaatat tgctctccgt ttttgaatac acacttgaca ctaataagta 960tcacagaaaa aaagaaaata taataaatta gtattgcgat atg 1003171003DNASaccharomyces cerevisiae 17aaaacggctc ctagttatcg tcagttttga taattagtaa ctagaatata gtatcaccaa 60gaacaggcca ggtaatatac tagaagttgt gtataactac taatattttt atacatatag 120atgccaagtc aaggtccaat tagtagattt ttcactctac cttgcattat tacctgaaag 180atcgtttgtg tttccttaaa ttcgccagag gtgcaaacga atgtaaatat ctacatcaat 240ttacggtttc acgcccgttt cgtttctaat ggcaactcat gtaaactgtg ataaacccgt 300tatttcagtt ttattttctg ctagtataaa ggatgatagt agccatttcg ctggaatatg 360tatcgggttt aaaagatggc atagttcgaa acattttcgc acaagattct aactgtcttc 420gaacgtcgta gaaaccgcaa cgcaagaaat gacagcgcaa taaaatttat tttactaact 480gatagaacaa atgtaaaaaa tttcataata tcaagtagaa ttctttattc tctttgtgaa 540ttcctaaacc catgaaaggg acttgtagta taagctggat acctattttc attggcttcg 600tttccaaatg acacaaaacc atcacaaaag gaaatagtcc ttccatagtt acccaatcat 660tctgttgcat attaaatgaa cagctccttg ttgataatgc cagtgtggca tattcaccgc 720tgcagttatt tcttttcata tataatgagt catttgtttc tgtcatcact tttctatact 780ttctcttccc cgcgtgtttt ccgtacacca acaatatatg ccataataca cgtaacattt 840ttttataaaa agaaaaggta agtgatatat ataaaatagc gccatgagta ggaaactttt 900ctgttactgc agatatgtgc cagactggct caggtggcat aaacacagat taatagtatt 960ggcgttgctg aaataagaag atctgtaaca atatcttaca atg 1003181003DNASaccharomyces cerevisiae 18tctaaaaatg ttcaggacta catacatcaa ttaggtttca ttccaaaagt accttttgtc 60aatttatacc caaatgccaa ttcacaagca ttagacttat tggagcaaat gctcgcgttt 120gaccctcaaa agagaattac cgtggatgag gccctggagc atccttactt gtctatatgg 180catgatccag ctgacgaacc tgtgtgtagt gaaaaattcg aatttagttt tgaatcggtt 240aatgatatgg aggacttaaa acaaatggtt atacaagaag tgcaagattt caggctgttt 300gtgagacaac cgctattaga agagcaaagg caattacaat tacagcagca gcaacagcag 360cagcaacagc aacagcaaca gcaacagcag ccttcagatg tggataatgg caacgccgca 420gcgagtgaag aaaattatcc aaaacagatg gccacgtcta attctgttgc gccacaacaa 480gaatcatttg gtattcactc ccaaaatttg ccaaggcatg atgcagattt cccacctcga 540cctcaagaga gtatgatgga gatgagacct gccactggaa ataccgcaga tattccgcct 600cagaatgata acggcacgct tctagacctt gaaaaagagc tggagtttgg attagataga 660aaatattttt aggacaaaaa actataagta accggggaag tatagaatca ccatagatgt 720aagcttacag acaatgtgta tatatgatgt atatgaacgt atacaaatat atatatatat 780acgtgctctt gttgtagctc gtatatcaaa ttcctcctcc gacgcttatc ttaatcgtac 840tccgcggaag tttgttatcg cctcttgaat tctttctttt cgttcattta tgattagtca 900tctatagaca atattcatta tttaagcacc tagaatacta aactaaatgt ctaaatatga 960cacaaggaag ataagataaa aaaaaccaag cgcttagaat atg 1003191003DNASaccharomyces cerevisiae 19catcgggatc ttccgactcg tcatcagacg tcgaggtcat tatgcactcc ccgagcgatc 60ctgaatacgc tttaaaatca caaactctaa gaagctcgag tcagaccgtc attaatagta 120agagaccagt aaagatagaa gacgaggaag aagccgtagg aatgtcacag ctcaattata 180ggtcgtcatt aagacaagct cctccaagag ctccctcaac tttgtcatat aatcactcga 240agaacaacga aacgccaatg caagatattt tcacaaatgg cgaaacagca aataacagaa 300agaagaagag aggatctttt gcaaggcata gaacgatacc aggatctgac gtcatggccc 360aataccttgc acaagtgcaa cattcgacat ttatgtatgc agccaatatt ttgggcgcct 420ctgcggaaga caacacgcat cctgacgagt agtatagctg tgctgagcct gaagtataat 480gcatatccat cggactattt agacaaagcc caaggaagcc taaggcggcc tgccaaggtg 540tttctccctt tttttctccg atttctttgt ataaactaaa taatatagtg attactaatg 600gaatggcggt attatgcacc taacctgttc attctgccac agattacgta agcgatttat 660tgccggcact tgttgtctta atgaccgagt caccaatgtg gaacgataat tttctctgac 720tcaaacctgt taattttttt ctacttcgtt tcgttagcga cgacgtcaag ccgcaggatc 780ctgtctgcct tgacctcttc tctaccttca gaacttacac ttttcaggta agatgacctt 840tatataaaag ttgacactat tacagttgtt tataaacgtc tgaagaatga gacgttttta 900taaaatgaat aaaatgcata ttctaagttt aaaacaacat tttcaaagtg tacgattgta 960aaaagagagg caattagaga atctcaaaca ggtaataata atg 1003201003DNASaccharomyces cerevisiae 20gaaatccaat gagaataccg cataatcttt cccaattacc ttgatattta caaaagacca 60tagatcctta ccctggtaaa gcttgtaatt ctgtgaatcc gttccctcca attggatttg 120attagtggaa gtcaacttgg acagtaatgt actacccggg tttttatgca ctccatagat 180caaaggatat ggaaaccaaa attccgtcga caattgtggt gactcaaaga tcaaatggtg 240agtagtcaaa tgtaaagtac cttgtgtggc cgtacctctt ctatgcagca ctacattaga 300tactttggca atcttgatgt actccatctt tgcggaatgg tatactattt cttttccctc 360tttttagcac tattacaccc cgcccacaaa ataaaaataa taacgacgac ctaatctcac 420caagtgaccc ttgtaaaacc tccttttctt tataatgttt cttttcttac taatatttgg 480tacatttagg gtagtgataa aagaatggca acattgttat tattgtgaaa aatgaggaaa 540atagaaaatc agaaacccta aaaagtgatt ttaccctatc agaaatattc aaatgtccta 600attaaaaata gtaaatcccc taaacattca gattgtaaac tagggttgag aaaatgactc 660atccaccact gtcttctttc ctgcggcatt ctatagatta ttgtgaatga ctcttattga 720tgagatggca ataacttttg aatatcagag ataggaacct ccatgtcgta acgattgtgt 780caccttgagt aagcatcgag aaaatccaat cttttttttt ccgtcataag catttctgcc 840atgctatttg tatatatata attactaata cgtcttctat agtatgcctt atctcttttt 900tgaagcgcta tttaagttta agcatcgaaa aactaacatc tatagttaaa attagttcta 960taaaggaaga gcaatacagt acatagacag gaagaaaaga atg 1003211003DNASaccharomyces cerevisiae 21gaattacgag aagcccaatt gaccatcgaa aagctacaaa ggaaacaact acactacaaa 60aggctactcg atgaccaaag aatggtcctc gaagaagtgc aaccgacttt tgataggtat 120gaagccacaa tacaagaaag agagaaagag atagaccatc tcaagcaaca attggagctc 180gaacgcagac agcaagccaa acaaaagcag ttttttgacg ctgagaatga acagctactt 240gctgtcgtaa gccaactaca cgaagagatc aaagaaaacg aagagagaaa tctttctcat 300aatcaaccca ctggtgccaa cgaagatgtc gaactcctga aaaaacagct ggaacaatta 360cgcaacatag aagaccaatt tgagttacac aagacaaagt gggctaaaga acgcgaacaa 420ttgaaaatgc ataacgattc gctcagtaaa gaataccaaa atttgagcaa ggaactattt 480ttgacaaaac cacaagattc ctcatcggaa gaggtggcat ccttaacgaa aaaacttgaa 540gaggctaatg aaaaaatcaa acagttggaa caggctcaag cacaaacagc cgtggaatcg 600ttgccaattt tcgacccccc tgcaccagtc gataccacgg caggaagaca acagtggtgt 660gagcattgcg atacgatggg tcataataca gcagaatgcc cccatcacaa tcctgacaac 720cagcagttct tctaggcagt cgaactgact ctaatagtga ctccggtaaa ttagttaatt 780aattgctaaa cccatgcaca gtgactcacg tttttttatc agtcattcga tatagaaggt 840aagaaaagga tatgactatg aacagtagta tactgtgtat ataatagata tggaacgtta 900tattcacctc cgatgtgtgt tgtacataca taaaaatatc atagcacaac tgcgctgtgt 960aatagtaata caatagttta caaaattttt tttctgaata atg 1003221003DNASaccharomyces cerevisiae 22tgatgcagtt ggagtcggta gcgatgttat aggaggagga ggtgcactag gaggcaaagg 60aggcgccata gcatccgtat gggggggtgg tgcgttaaaa gcattcgatg atgtttgctt 120atgtaatttg gattcaattt catccagaaa cgacatacca ttttggctac tctgtttagg 180cgggtttata gatggagaaa taggagaagg tcttacgtta tcatccttag atgaacctat 240tacatcctct tgtttatctt gggtagtgta tccagtatca ccaccaacca cgaatctatc 300atctctcttc ttttggatct cagcaagaaa tggtaagggt cccccaggtg ttacggccga 360ggaagaactg gatgaagata ttttggattg cttactggac gctgagggtt tgtttgtcgt 420gagtgttgga ggaggaggag gagccgatgg tactgacgtt gcaaccgaag gaggaggagg 480aggtggtagt ggtgctaaag gaatagatga tgctgacaag gcagaggatg ttgaaaaagc 540accaggtggt gggggaggag gaggtggtgg cgcgggcatt gacgatgctt tgttaggagg 600aactgatgta gtatttggta acggtggtgc taaagttggg ggaaccgggg ttgcttttac 660gctgttagtc gacgcagagc tcatggctgc tggtagtggt ggtggaggcg gagctggagc 720tgaagttgct tttttaggtg cagaggtcac atttggtaac gatggtggag gtggtgcagt 780aggcggtaat ggcggagcat gtgatgtagg aatgggcgga gcagatgatg gaagtggtgg 840ttgtgaagga gatttatgat tttcggtttg aatctttgtg gaagaaacgc cctcgacggc 900tcctcgttca gacctcctgg cattaatttc tgccaaaaat ggcaacccgc ctgcaggaac 960ttcagaagat ggtggtgaga ctgcgttatc tgtaggttta atg 1003231003DNASaccharomyces cerevisiae 23tgaataagcc tgtataactg cgcatgtaag aatagtggct gcaatagatc ccacagcagt 60cagtgctcca gcctgctctt tcaaatccgt cgtcgtaagt ctatcaacag gtaatcggtc 120aaatgtgaca ttatttgaga ttcccaacca aaatgtgggg taccaaagta ttacttttgc 180tatgggcgat ccattttcta gtgttctttt caccgcactc ttccaaacga cgtataaaac 240aaagcataaa ggtaaaagtc tttgaaatcc cacactgaaa agctcataca cgctagctgg 300gtcatgtgca tccgttagta atggagggtc tagagataat acaagagtcc aatagcccac 360tatcgtgttt atccagtacc cgtaaatact gtcatacaaa taaaatattg gcagtccaaa 420aagcatattc aatgcgacca cagctgctcg aggatcataa cagcccgaca ggataccgcc 480ttgtatatct ctgaatgaat atgaaccggg aaaaaatgaa ttgaatgcta ctgaaaaccc 540agtgttatac attccttttt ttgatggaaa agaattttgg gccccttgca tagaaacttt 600ggtacagcca ccgtaaaatg gtgagataac acctgcatgt actgcagagg cgcatggaaa 660cgagtcactt ctataagggt aggacacgac catcgggtct tcttcgctaa acagggcacc 720tccgccaatt tcataccctg tatatttgac tctcctattc cctacggcaa tggcggagta 780tgtccatcca cctctatcac acagtgctgg acatctgatc atgtattctt tattatcaag 840tggaccgcag tttttagcat ttaaaccaca ttcgttattg gtaccctccc agttcaagta 900ggaattgcaa cttaaagaca atataggaat cttttctgag ccatcatttg gatggaagta 960tggcggcttg ataagatagg ggtatatgag agaataaaaa atg 1003241003DNASaccharomyces cerevisiae 24ctggctattt atataagatg ttgctctaat tccatgagtg atgtcccatc gcatgatgaa 60gaagttatga atgaagtgaa caatatcatc gaattacaac aacggcccat gcaaatgacc 120aagtctaccg tacgtaccag gagaagacca ccaccacctc ccattccttc cactcaaaag 180ccatcgttga cagaagagca aaccgaaagt ataagaatgt cacgccgtaa taaagatgag 240aacaatgcta aaagagttgc cccaccaccg ttgccgaaca gacagttacc taacttagac 300gctaatactt actatgtacc atcctcacaa aatgactatg gcatgtatgg tgctttcatg 360gataaaaaag cagatgaatg gaagagaaga gtaatggact caattcaaaa attgagcaat 420caagacacca cattgatgtt cttttcggat ccggcattaa gtttggaaga cagtattcgc 480agaattaggg agaagtattc aaactaaata cactgttatt tatatacatc gggagggagt 540ttaaaaattg tatacactaa agtgacctta tgaattggag ccattttcaa cgttttagag 600tgatgttgca tccttttcat cagatcggga aattaaaaaa acggttatag aagggctaaa 660tgtaaatatg taaattttat gaagtcaaga gtaaagaaaa tcttcggttg ccgatcaaat 720acactcttac aaaataccct aaactcagtt tatctttcca ttccaactga ttatcgcgta 780cgccttggtg accaaccata ccctaaaatg tcaatttccg gggcggaagg ggtccttaaa 840ctgcaaagcc tcttcccatg taaataaaat aaatccgtag aatttattaa atattgtcat 900attataagtc gggaaaggcc ttctgaatgc acgtatattg accaaataga gttagattca 960aattatttat tacatttttt cagcatcgaa gttaagtaga atg 1003251003DNASaccharomyces cerevisiae 25ggcgaaagag ctgtgtatga gaataacgag accggtgtca ttaagaacct ggaattgcaa 60aaggccacca tccagggtta cgacaatgac atgaggccag tcatccttgt gagacctaga 120ttacatcatt cttccgacca aactgaacag gagctggaaa aattctccct gttggtcatc 180gagcaatcaa agcttttctt caaagaaaac taccccgcat ccaccaccat cttgttcgat 240ctgaacgggt tctccatgtc caatatggac tatgcccccg tcaagtttct aatcacttgt 300tttgaggctc actacccgga atctttgggc catctactta tccataaggc cccttggatc 360tttaacccga tttggaacat catcaagaat tggctggatc cggtcgtcgc gtccaagatt 420gttttcacta agaatatcga cgaattgcac aagtttatcc aaccccaata catccctagg 480tatctgggcg gagaaaatga caatgatttg gatcattaca ctccaccaga tggctctttg 540gacgtccatc tgaaagacac cgagactcgc gctatgatcg aaaaggagag agaagaattg 600gtcgaacaat tcttgactgt cactgcccaa tggattgaac accagccatt gaacgatcca 660gcatacattc aactgcagga gaaaagagta caactttcca ccgctctttg tgaaaactac 720tccaagttag atccgtacat cagatcaaga tccgtttatg actacaatgg ttctctaaaa 780gtttgagcca agccacgcga cgctccatac tgtatagacc tttattataa aaacatctat 840ttctttatat gtccctctat cttatttttc ttttactttt atttgtataa tacgcgaaaa 900attatagaat catttattat caaaaacaat caactatgaa atgaaaaaca atacgcctgc 960taatacggtt cgcccttcaa tttttgtttt ttttacatga atg 1003261003DNASaccharomyces cerevisiae 26agataagaat atgagggtaa caatgaatga gaactcactt tgtaatcacc agttgaagaa 60tggtaaacaa ggctagtaat acatcctggt atttcggtct catgttcaaa ataatcagtg 120gtaatttata ttatgtatat cttttccttg tttctttgtt aagcttttgt gtaaacatac 180tttagtaatt gtgacgtttt ttggcacttc gcacaggcgt gactagtttc tgtgaacaga 240gggcgtctat tcatgatctt cacaaatctt gggggagtta atttactctg cttccacatt 300acattgatgc gcagtgatct actgacgcct gctggtggtg agtacacatt agataaatac 360ctagggtgtg cagcaataga ccttaaacaa gggtgagctt tgcctattag agaagaacct 420ctaactgcgc ttttcaataa tagccaccga acaattggca tattatgcaa cctgtgtttt 480taagtacctt tttatgtcag attttttgaa ctatccttcg attgttattt cttgatataa 540cgtttacatg atttcttaat ttacaacgcg gacgaattag attgaaatta tttagcatat 600ctgtctaaga gcacattaga tcgaagtacc gtagcacatc tgccatacta tcaaatgcat 660catcacgaaa aggcgcagtg ttgatggata gtaaatatga aaaggatctc ttcttaggtg 720ttccaagcct cgcttcacgt gtaacataca cagtttagaa gtttaccaaa ccgcggcaag 780gcgctgtaag gttcaagagg ctttgaatta tgctatctta ctatcttgcc gcaagttgct 840gtcaggtgta gttcctaggc ggctcgttga caagaccctt ctgcccaatg acttctatat 900aaagtatggt tttcttttta aatacagtaa ttccatgaaa aaaagagggc caaaaagatc 960aagcaataaa ccaaccgata tataaaacac agaactgcag atg 1003271003DNASaccharomyces cerevisiae 27acagaagtaa gtaccggggt acctaaatat acgcataaaa gtctctttct tttttttttt 60ttttttttta gcttcctaca tttcgttaat aatattatat agattatatt tatatttaag 120aaaagtaata tcagcatatt atgaatagac aaaaaagtct aaggtcaaga tttattaaat 180gttagattat taagattaca attaacaaca tttgttgtta cttcataaaa tttcgttact 240tcataaaaga actacagtcc cccacttcta aatgagtggt tgtaggggtt catatacctc 300ccatactgtt ggaataaaaa tcaactatca tctactaact agtatttacg ttactagtat 360attatcatat acggtgttag aagatgacgc aaatgatgag aaatagtcat ctaaattagt 420ggaagctgaa acgcaaggat tgataatgta ataggatcaa tgaatattaa catataaaat 480gatgataata atatttatag aattgtgtag aattgcagat tcccttttat ggattcctaa 540atcctcgagg agaacttcta gtacattcta catacctaat attattgcct tattaaaaat 600ggaatcccaa caattatctc aaaattcacc aactcttcac atacatacct gcggtagcaa 660gataggtaca ctttttctac gtttcacgaa ggtagcgata ggtacctcac tcattgtagg 720tgcgggggta gcgatggagg tttctgtacc attaccacca cagccactat actcacgtag 780tgaagtccct agcgtggaat tgtgtggtat cgttgctatc tgtcgttcgc caccctcggt 840atatccaacg tgcaggccaa tatcactctc taagaaaatc gtatcaggat tggtacggac 900aaactcttca tagcctacgt cgaaatcaaa ttctgctaaa gctgtgactg tagttaaacc 960taaaaccgcg attattgctt gaaaaactgt ggagaaattc atg 1003281003DNASaccharomyces cerevisiae 28tgtcatcgcc gccagaacgt gctccttact gtgggacgtg ccactggtgg gagtaaacca 60ctgcattggt cacatcgaaa tggggagaga aatcactaaa gctcaaaatc ctgtggtact 120gtatgtaagt ggtggaaata cacaagttat tgcatactcg gaaaaaaggt accgtatctt 180tggtgaaacg cttgatattg ctatcggtaa ttgtcttgat agatttgcaa gaactctgaa 240gatacctaat gagccctcgc ctggctacaa catcgagcag ttagctaaaa aagcccctca 300caaagaaaac ttggtagaac ttccctatac agtaaagggg atggatcttt cgatgagtgg 360tatattggct tccatcgatt tacttgccaa ggatctattt aagggcaata agaaaaataa 420gatcctattc gacaagacaa cgggcgagca aaaagtcact gtagaggatc tttgctactc 480tctgcaagag aacctattcg ccatgctagt tgaaataaca gaaagagcta tggctcacgt 540taactccaat caagttttga tcgtaggcgg tgttggttgt aacgtgcgat tacaagaaat 600gatggcgcaa atgtgtaaag acagggccaa tgggcaagta catgctacag ataataggtt 660ttgtatcgat aacggagtta tgattgccca agcaggacta ctagagtata gaatgggtgg 720gatcgtgaag gacttttctg aaactgttgt tacgcagaaa ttcagaaccg atgaagtata 780cgcagcctgg cgtgattaac gatttttgtt acagttagcc taatgttcac actacgaata 840tatatatata tttatatatg ccatacacct tacatttaca gctcagtgta taaccttgtg 900gaagcgcgaa aataagcaag agacatttga aaataatcaa taaacaaagc tcaaaaaaat 960tagatcatca cctaacaaaa taagacgtgg caattacaga atg 1003291003DNASaccharomyces cerevisiae 29ggcaacatag cagtacgtcg ccaaaaagaa cgaaaacaaa atagatatta tgcataaact 60aacgtgattt tcatacagat attgcaattc aggcaattgt ccatcagtca atttccatct 120gatagccaaa actaagacca aagttgtaga catggcaatt ccattgatct tatacgaaag 180cttcgaacca tcccttaact gaacaccctt catgactctg cccggtaaaa tgacgtccaa 240aactgccagt attccatacc acaggcaata gacagtccat aattcacgat tgcccagata 300gtagcgcaat ggcttgatac cgttccaaag ctcaactata tcgaaattct ggaaaaatcc 360cttaataaaa taatcgggcc ttatcatttg attcaagatg atagtgaaaa caggcagccc 420tatgctgatg cctaaggcac caatcagccc accaaattca aactctgtag ttctgggatt 480caaagctgat accatccttt tattctctac accgaatttg tctttactcc tatgctgttt 540acaaggtcta tctgataagc aattgcgcaa gaaaatagta gaatgaaaac tgattattaa 600aaacaaacgt aaactcaagc ctcacttgat gctcagacgg agtacgtgaa aaacgtccgt 660tatgcaaaac cctttatatg cacaaccttc

acacaatgca aatttccgat gatgcctaca 720tacaaaagag cgaaaggcga tataaatttt tttcacggga ttttcgttta ggtgaaaata 780aaatgaacga cagagcatgc agagtccggg taatacatat gtttcaatac tgtttcaata 840ctgtttcaga agtgcgtcac atattaattt taacttataa ctggcctgtt gctggcaaga 900ggtatatata tatgacgaat gtgaccaaca taagtcctta agataatccc gaaatatttg 960gttaggatga ttccctttcg aatttgtgaa cgttgatgat atg 1003301003DNASaccharomyces cerevisiae 30ctagcggtct acattcgcta tcaactgaac gaatagtgat gcaatctgaa ccttaaactt 60ttcgctcgct tttactttcc agaaaaaatt ttcttcattg ggattcctct gctgacaaac 120gggctcacag aactgaggaa acgagaattt tgttaatcaa agcaacatta cgggaaggaa 180cggaaccgtc tcgttgctgt gggcgcgagt tcgacgcaag aaaaaaatgc tgcagcatcg 240tcttttgtga acgccaagaa ggagtccggc gaaggtattg ggcgtcacaa ccttttattc 300tccgcagtgt ctcttgccta caaagcctgc agaagctttt atgccggggt gtacgtatgt 360taatcagtta ccctttccta ctgtgtgccg cacccctcat ttgctctcga tacgagaagt 420tccgcgccga ttctggcctt tttgttttct ggctagccta ctttcagggg acgtgccttc 480ttatgccgct gtaaattaca gcagagattt agatctgagt gaaaacgtgg cgaggaaaaa 540gggtacaccg ttaaaagcgt agacacaatc ccactttgtt gtgcctagtc ttctctgctg 600tattttaatt ttctgtttga acttttttcc gttcttttcc atcattgttt aatttttact 660ttgagtgggc ttctcaaaag aaaaaaatag ctggtattgt atttttaccg taggcgtttt 720ctttgtattt ttcccaagag cagcagcacc ttttatatac cttggttaca cattgtaagc 780ctcaaaaatc gtcctatgta agtgtcttat cgcatcatac ttaaggtcaa acctgtaaag 840cgcgcttcta gttttatttc tactactcgc cttggctctc gagatcgctt aggtagttta 900atagttagtc acacccaccc acccattcgc ttagaatata gaatatagag cagttgcagt 960acacgactca ttttagcaac gataagagta taaattggaa atg 1003311003DNASaccharomyces cerevisiae 31tccttataac ctgtaaaaaa aaaaaaaaaa aaaaaaaaga agggtttaaa taaaaatcgg 60acttactcaa agggttgaaa agcactttaa tataggtttt tagtttcggg taagaagatg 120tgtcaaaggt ctcgaaaagg aaacattagg gcaaatacgt aaaggttgcc ttcgtatctc 180gtttccacag caacgagaaa cgagatacga aggcaactga ttcccagcat ataaaaggcc 240atgaattttt ggcgtttcct attgtctttt cgaaactatt tctttcattc ctttcctttc 300ttgttctttt acttataaga aaaataatat acgtatatat ataactacaa accacatcag 360caataaaaaa aaactatatg accatggacc aaggccttaa cccaaagcaa ttcttccttg 420acgatgtcgt cctacaagac actttgtgct caatgagcaa ccgtgtcaac aagagtgtca 480agaccggcta cttattcccc aaggatcacg ttccttctgc caacatcatt gccgtcgaac 540gtcgcggcgg tctttctgac attggtaaga atacttccaa ctaagagcat gcttctcttt 600ttttttgtag gccaatgata ggaaagaaca atagattata aatacgtcag aatatagtag 660atatgttttt atgtttagac ctcgtacata ggaataattg acgttttttt ttggccaaca 720tttgaaattt ttttttgtta cctcgcgctg agcccaaacg ggctccacta cccgccgcgg 780tcgccatttt gggaagtcat ccgtcccaaa aaggaaatag ccataacata tcgttactgt 840tttggaacat cgcccgtttc gcccgattcc gcctcagcgg gtataaaaag agatcttttt 900ttttcctggc tgtcccttcc catttttaaa tgtcttatct gctcctttgt gatcttacgg 960tctcactaac ctctcttcaa ctgctcaata atttcccgct atg 1003321003DNASaccharomyces cerevisiae 32aatggcaaac tgagcacaac aataccagtc cggatcaact ggcaccatct ctcccgtagt 60ctcatctaat ttttcttccg gatgaggttc cagatatacc gcaacacctt tattatggtt 120tccctgaggg aataatagaa tgtcccattc gaaatcacca attctaaacc tgggcgaatt 180gtatttcggg tttgttaact cgttccagtc aggaatgttc cacgtgaagc tatcttccag 240caaagtctcc acttcttcat caaattgtgg gagaatactc ccaatgctct tatctatggg 300acttccggga aacacagtac cgatacttcc caattcgtct tcagagctca ttgtttgttt 360gaagagacta atcaaagaat cgttttctca aaaaaattaa tatcttaact gatagtttga 420tcaaaggggc aaaacgtagg ggcaaacaaa cggaaaaatc gtttctcaaa ttttctgatg 480ccaagaactc taaccagtct tatctaaaaa ttgccttatg atccgtctct ccggttacag 540cctgtgtaac tgattaatcc tgcctttcta atcaccattc taatgtttta attaagggat 600tttgtcttca ttaacggctt tcgctcataa aaatgttatg acgttttgcc cgcaggcggg 660aaaccatcca cttcacgaga ctgatctcct ctgccggaac accgggcatc tccaacttat 720aagttggaga aataagagaa tttcagattg agagaatgaa aaaaaaaaaa aaaaaaaagg 780cagaggagag catagaaatg gggttcactt tttggtaaag ctatagcatg cctatcacat 840ataaatagag tgccagtagc gacttttttc acactcgaaa tactcttact actgctctct 900tgttgttttt atcacttctt gtttcttctt ggtaaataga atatcaagct acaaaaagca 960tacaatcaac tatcaactat taactatatc gtaatacaca atg 1003331003DNASaccharomyces cerevisiae 33ttcttttttt tttttttttt ttctttttgg gaacggggga aaaggtctca ctagtatata 60aaggaaagag agtacagcac gaatgagcca gctgcaggaa aggggctagg ttaaaaaata 120aaaacccagc agaaagcaaa caaccaaata taatttagaa atggacagag accatattaa 180tgaccatgac catcgaatga gctattccat caacaaggac gacttgttgt taatggtttt 240ggcggttttc attcccccag tggccgtctg gaagcgtaag ggtatgttca acagggatac 300actattgaac ttacttctct tcctactgtt attcttccca gcaatcattc acgcttgcta 360cgttgtatat gaaacgagta gtgaacgttc gtacgatctt tcacgcagac atgcgactgc 420gcccgccgta gaccgtgacc tggaagctca ccctgcagag gaatctcaag cacagcctcc 480agcatatgat gaagacgatg aggccggtgc cgatgtgccc ttgatggaca acaaacaaca 540gctctcttcc ggccgtactt agtgatcgga acgagctctt tatcaccgta gttctaaata 600acacatagag taaattattg cctttttctt cgttcctttt gttcttcacg tcctttttat 660gaaatacgtg ccggtgttcc ggggttggat gcggaatcga aagtgttgaa tgtgaaatat 720gcggaggcca agtatgcgct tcggcggcta aatgcggcat gtgaaaagta ttgtctattt 780tatcttcatc cttctttccc agaatattga acttatttaa ttcacatgga gcagagaaag 840cgcacctctg cgttggcggc aatgttaatt tgagacgtat ataaattgga gctttcgtca 900cctttttttg gcttgttctg ttgtcgggtt cctaatgtta gttttatcct tgatttattc 960tgtttcattc cctttttttt ccagtgaaaa agaagtaaca atg 1003341003DNASaccharomyces cerevisiae 34cgctcccacg acatgcgcat ctcttccaaa aacactacca ctttctactg actcactggc 60catttgagaa ccacagagac ttggtagatt ccatcgctgt aaacaatggg aaactaaatt 120caacgtcttc aaggagcgtc tggctgaagg cggattggat aacactgttt aacgttaaaa 180acccttgggt ccaaacgccg ccatcgttaa tgcgtctgag tgggacagat cttgatacct 240tcacaccaga gaggatattc ctgataaatt ctcttggaaa ccactacaaa tttttaatag 300cgaacagtca tctaagctac aatcacaaaa aatacccctc ccctggcgtg caaattcctg 360tcaggaacgc tcttggcgaa gtttctccgg ccaaacaaat tgcccaactt ttcgcaagac 420agctgtctca tatttacaag agcctcttca tagaaaaccc cccgctctct cctgagaacg 480agctggcatt gactgccgtc ttctatgacg agactgtaga gcgacgcctt agaaggctct 540atatgcgagc ttgtgcaagg gcatatacga ctactaatgc cgactccacc acggagcctt 600tgatgtttca ttgcacccgg tgggaagttg attagttgtt gttggctgtt atactggagt 660aaatgtcacg tgccactgtg gccgtgtcag gtcacgtgaa gagagaaatt cggccacagt 720tgtggtccta aacaaggact gaaaaagatc gcagaaacta gcaacgtcgg atagcggtat 780ggttgaacca aagtccagtt tttagtcata gccggttgag ggatgatctg ccgttcagtg 840ttctgcgttc aataatacgc atatatatat atatcaaggt atcaacacaa tacttgaaca 900ggttaggctc gtactaaagc ctggaagttt ttatctttct gtaacatttt tctttcttga 960ggtgtgtgtg tgtatagatt agcagggaat tatctaagat atg 1003351003DNASaccharomyces cerevisiae 35cgactaacct ttttcttggc agtatggaga ctgactaggt ctcccaaaca ttcattgtaa 60ctgctgttta aagattttgt tctaacctaa attcaagtga gaagctgaac atgtgtctct 120acttatgata tcacgacagc aaatactaat cttgccataa atagtctagc gttttgcaac 180ttacctctag atatatttta tttcttgagg aaccgttttc gtcggtaata acaaaatact 240actgaaacgc cacagcattg agagaatacg ttatcgatta cggctttctt ctcgctccag 300atgtcgcggg taagatattc acctcaaact tttcttgttg agtgtcgtca caaatctaga 360acctacatgc catctcaacg atttttctgg agaaaggcct cactccgttc cgtacgtaat 420gcatagataa agtatcagga tcttcacgat gctcgagagt tacttagtag tctgagttta 480tgcgaaaaaa actccgccgt tgtaataatc gggaatacac agaagtagta ctgcactatc 540actgggatac tcaaaaacct tctttttaac ttttctatcc cacaaataga acataggaaa 600gaacattgac tcctccactt gaagttaaat tacaggaaca aacgcctaac tataatttcg 660acattgttgc atcaacgaat cgaccgaaag aaaaatctgg agttgcagtt atcacttgta 720tgtgcactaa gatttatatt tttactcctg agatctgcca aatcggtagc ttattgaact 780gcgttccttt ttcccctgag ttctcgaggt acctgcggct ttgtctgtgc catctccccc 840actttaaagt accccacgtt actaccgcgt ttttccccac ccccggctta ataaattagc 900tatatcttgt tgacttaaat acggagaaaa gaagaaaacc ttcaagaaat gcttcattgt 960cttgtcaaaa gagctaaagt aaaagagctc tagttcgaag atg 1003361003DNASaccharomyces cerevisiae 36ctgtcgagtg ctggtggcgc ttgatagcgg tattgtactt aataggtatc gccttcattg 60gtttgaaatt ctcgatcaaa ttctgcagga tagggtcctg agcaggcaca gaggcttgtt 120tcagagtaag ggtctccaat ttctgtttaa gggcatgatt ttccgattct ttcgcttgaa 180gttcattttg gaggcggttt agtttcgttt cgtagttttt aacgacctta ctcagtgact 240ctatggtttc ctccagcact tgcaacttgt tgtttttgcg ttctctgtag gccctttggg 300cgtctctatt ctgccgtttt ttcttctgta gctcctcatc attttcttca gtttcgtaat 360cttcgtgaag tcgatgaact cttttcctcc gctgagctgc tctatggggc aaccttggag 420gcagtttcca atttttggac acgtggatct tggacaaaag agcgaggtgg ctttcctcag 480actccttagg ttttatcaga ggtagagcca tgactgtgat aatatgctag ttacactgtt 540tatgttgtgt gaacttgttg taatatggtt aacttcactt tcagtgattg atatgatagc 600gacatcactg ccgtgcaaaa agaccattcc attactgcac ctttttgtcc ttttccgtgg 660aataaaagtt cactcgtcag ttccatgcat tctggaaaaa aatgatctga aagatgccac 720agttgtgggg cccgcccggc ccaataggta aactaaaata caatagaagg ggtactgagt 780gcacgtgact tatttttttt ttttggtttt aggtttcgct tttttcacct ttttctactt 840tctaacacca cagttttggg cgggaagcgg aaacgccata gttgtaggtc actggcgtga 900gtcaaggccg ggcagccaat gactaagaac acgaggtaac ttgaatttaa ctatttataa 960ccagtggtag ttacgaagac aaattgtttt gttcgtcaat atg 1003371003DNASaccharomyces cerevisiae 37caattttgaa aattgacata taaaactctg attctgcaaa gcctcttgcc ccaaaaagat 60tcaatagcat gcttaaaacg aacgcgattg caacccaggc agcaggattg accgatggtg 120cccaataaga gatggtaagc gaacatccta ccagctcgct agggtaagat atgagccaca 180tcaataagta gttaattcct atactgaagc cgactgatgg gtctataaat ctactggcgt 240gcagcgcata ggagccggaa acagggtact gacatgaaag ttcggcccca cactgaacaa 300cacagagcat agatgcgccg accaacaaga aaccaattag caaagaagca ggtccggacg 360ctagtgattc ccctaaacca atgaaaagac ccgtccctag agtacctcca atggctatca 420tggtcaggtg tctttgatct aggacctttt tatacggctg gttggctaag tcccattgta 480ttttttcttc ctctgaaagc tccgaataca gcaaaccttc ttggatcgct ggtgaatcat 540ttcgcttgaa agagttcttg aatctgtgta ttagattatt tccttcattc gaaggcgtac 600ttaacacgct agtggaaaac tgaaccttcg aaagtttggt agattcaaat tcatccattt 660cgggtatctt tcatggtatc ctgatggaga actcttgacg gtgattactt aaccacccaa 720atctgtaaaa tatatacgca tttatttcct ggcatctctt cgctatcccc gcaaaaagtt 780aatgaaaaaa agccattcct gcaggaactg tggaaaagta aaaactgtgg catgaaagta 840ctaccaaatt gtggcgaggt attcaatggt aatagcaaaa cagcaacaac gccaatttga 900aaatgtacta ctaaggaaga taatttaaac agacaagttg tagaagaaat ctgaatcagc 960aacttttagt gtgcaacttg aaaaagtaat caaaaaacag atg 1003381003DNASaccharomyces cerevisiae 38cagttttctt tttgaatgaa ggagaaaagt gttctagaaa tatgttttag ttctaagtat 60cgttgtctgg agcaagcaaa gaaaagcaga cctgtatgtg caactttctt gttttccatt 120aaaatctcaa gaaccggccc cttgactgtg ctcatatatc aagtatcggt tttaaagtcc 180cctaattgtg ataattgcaa gaatgacagt caaaaagata tttttctttt ctttcttttt 240acctatcctt catgaaaata cctatgctga tactgaatat cttcatttgc agctatgcaa 300tatttcagat actgcatttt acccaagagt ttctttactg gtggttggat tttttttaag 360acgagaagat taccagtcct ggatgttcat gaatgtgcct attgcgtcat cagcgactcc 420gcgccaagaa aagaaatact cgcatgctcg gatttataga atcgcataat ggaaatagct 480tccttaaagg atggagataa ggaaaaaatg acaagaacaa ggaagtactt gggagctttc 540tccgacatgt taaatatttg aaactcacgc agctctcctg gaaagttgca tctggaaagg 600taaggttgtt ttttgttcag acatcaaaat cggctcttgt agacaatgtc acagatccac 660aagttgaaaa aaaagtttcg atgaactgga taaggggaga ggtcacaaac aaagtgtagg 720gggtgagtag tatagtggta acttgttcat ttacctaaat aacattctca ctagaaaaga 780gatattgaaa gactcctcgt ttacctaact tggctggttc ttaggtatat aatagaaaca 840tggatctggc aggttattac ttacagtttg cattcccacc aggtaacaat tttcattata 900tatagttatt ttttaccacc acttcttctt ctttcacttt gtcttgcaat agaaatacca 960aaacaaggtg aggaaaaaat cgaatctcaa cgataaaaat atg 1003391003DNASaccharomyces cerevisiae 39cggttggatc ctcacttgtt ttaacacctc caaataacaa gtttttaatg aaggacattt 60gttctctata atattccgat gtacgtgtgt gtggctgatg agatttagac tggttagact 120atttgacgcg tctattatag cttactgcaa caagaaaatg atcgttgata tataaactct 180cagatgtata tatcgttctg gaaacatcga gcataataca atacaattca acaaaaatgc 240gagaaggcac tgatgtcttg tcgttaaaga accaaaaacg cggacactac gaccgtctta 300tttccggtag aaaaagggta catacagttg aaggaacgaa gaaaattaaa attagaaaaa 360aaagtaaaat aaaacaagga aggtagggta atatggtctc gtttcctttg tcgctccgca 420aataaaggag cttattcccg cacgctcaca tggtaatttg cgccaaatca cggatgtgga 480aaactgatca cgtgcttcga tcgccaacta ctgagcgtcg tcccacactg atctggcaca 540gcttacctcg ccttgaaaat tttaatctgt cctgctcgtt tgttgtatat tgcttcttct 600cagaatatgc ccgcgataac tgacaaagag ggttcgacgt ttcagagatt ctactcttga 660ccactgtttc gtgtagccgc tcaaggttta tttctttctt ctttaatgtt cttggcactt 720aggcggctcc gtcctccgtc tgaaattgcc gatcctatta tttgcggagg gctccttaga 780agggctcctt agtaagcagt ttgcgttcct gatataactc cgttcagaac aaggataaag 840tcgcaataac cattactaag cacagtgttg taagtaggac aactcgaacc tatataaggg 900ttgtgaactg tgcttgattc ttgcccatca tatgcaaaaa agtacgtact tgatatatac 960aacaactgta gttcagtata gcgaagttta aatttagaag atg 1003401003DNASaccharomyces cerevisiae 40tggaaatgta aaggataatg agtgagcata taaaatggaa gaaaaaataa taataggatt 60atgtataaaa tatcgattcc cttttgtaga tttcgagatc ttcgaggaga acttctagca 120cgttgtttac atatctaatg ttgtaacacg gcctttgtta tcttgtgaat atatccatca 180cctacgtcgc ttgaggtttc gtatcaaaga aagagagttc aaacataatc atacgtgttt 240cactccaaat ttgatcacaa atggccaccc attatagctt gttattattt acttcttctt 300gagttcattt tattgaaaga tgcccgctgg gaacaaaaca taaataaaat tcaagagtac 360aatatagcgt agcatagttg cgagcaaggg aaggcaacac agttaaaatg acaatgttag 420aaggaaaaac taaatcaagc tcccatagga aatttcttgt gtcagtaata tgtctcgaga 480aaataataat aattgaatct atttattgaa aagtaaatat ctcgtaaccc ggatgctttg 540ggcggtcggg ttttgctact cgtcatccga tgagaaaaac tgttcccttt tgccccaggt 600ttccattcat ccgagcgatc acttatctga cttcgtcact ttttcatttc atccgaaaca 660atcaaaactg aagccaatca ccacaaaatt aacactcaac gtcatctttc actacccttt 720acagaagaaa atatccatag tccggactag catcccagta tgtgactcaa tattggtgca 780aaagagaaaa gcataagtca gtccaaagtc cgcccttaac caggcacatc ggaattcaca 840aaacgtttct ttattatata aaggagctgc ttcactggca aaattcttat tatttgtctt 900ggcttgctaa tttcatctta tccttttttt cttttcacac ccaaatacct aacaattgag 960agaaaactct tagcataaca taacaaaaag tcaacgaaaa atg 1003411003DNASaccharomyces cerevisiae 41ttcctaagcc tttgagatat atcaaaattg ctgcctttac caacgacgaa agtaaattgg 60aagagcttcg tgagaaatac ccaaatcatt tgattggcgg agcagatctt gttgccaaaa 120ttaaaagcgg tgaaattagc gttgattttg acaaagcatt tgcaactcct gatattgttc 180cagctttaca atcgcaggtg gccaggatac ttggtcctcg tggggtttta ccctctgtca 240aaaaaggtac ggtgagtgat gatataagct ccttacttca agaaagtcta ggatctatgc 300ctttcaggca aaggggaaac tctatcagca ttggagtcgg caaatgctac ttcactgatc 360gagaaatttt acaaaacatt atatccgcta gagcggcatt taaaactgct gttgataatc 420aaaaatctaa gaaaccaaat atactgagta aaaccacatt atcaagcaca catggccccg 480gtattgtaat cgattttgct taatcagcga atcagttttg tcttgttgga cttttttaat 540tgtatatata tatatactgg tgcattttct ttctttttat ataaaatcat gtacatacaa 600agtaaccgtc tttttaaagt ggaataaagt aactgctctt ttatttttga ataatagtga 660aagtgtatgt tgcataatca ttagatacct atgtacaaga agtattcaaa tttatctgaa 720tagtatgtga aatttcaatg agacaaaaac cacctacctt tgagcttcct ccttttcaat 780atcttagagc cctgtttgct cttggcccta gccaagaaac caaaagttct cttccgtttc 840aatgtactag gttgataggt gttacccctt gatttccatc ttctttgacc tattaagcca 900aatcccaacg gtgtgaagga cggagtcttc aatggtgaac tgtttaagag cataccggtt 960tgtgggcgta acacagatag agcagagaaa gaagatatag atg 1003421716DNASaccharomyces cerevisiae 42atggattcta gaacagttgg tatattagga gggggacaat tgggacgtat gattgttgag 60gcagcaaaca ggctcaacat taagacggta atactagatg ctgaaaattc tcctgccaaa 120caaataagca actccaatga ccacgttaat ggctcctttt ccaatcctct tgatatcgaa 180aaactagctg aaaaatgtga tgtgctaacg attgagattg agcatgttga tgttcctaca 240ctaaagaatc ttcaagtaaa acatcccaaa ttaaaaattt acccttctcc agaaacaatc 300agattgatac aagacaaata tattcaaaaa gagcatttaa tcaaaaatgg tatagcagtt 360acccaaagtg ttcctgtgga acaagccagt gagacgtccc tattgaatgt tggaagagat 420ttgggttttc cattcgtctt gaagtcgagg actttggcat acgatggaag aggtaacttc 480gttgtaaaga ataaggaaat gattccggaa gctttggaag tactgaagga tcgtcctttg 540tacgccgaaa aatgggcacc atttactaaa gaattagcag tcatgattgt gagatctgtt 600aacggtttag tgttttctta cccaattgta gagactatcc acaaggacaa tatttgtgac 660ttatgttatg cgcctgctag agttccggac tccgttcaac ttaaggcgaa gttgttggca 720gaaaatgcaa tcaaatcttt tcccggttgt ggtatatttg gtgtggaaat gttctattta 780gaaacagggg aattgcttat taacgaaatt gccccaaggc ctcacaactc tggacattat 840accattgatg cttgcgtcac ttctcaattt gaagctcatt tgagatcaat attggatttg 900ccaatgccaa agaatttcac atctttctcc accattacaa cgaacgccat tatgctaaat 960gttcttggag acaaacatac aaaagataaa gagctagaaa cttgcgaaag agcattggcg 1020actccaggtt cctcagtgta cttatatgga aaagagtcta gacctaacag aaaagtaggt 1080cacataaata ttattgcctc cagtatggcg gaatgtgaac aaaggctgaa ctacattaca 1140ggtagaactg atattccaat caaaatctct gtcgctcaaa agttggactt ggaagcaatg 1200gtcaaaccat tggttggaat catcatggga tcagactctg acttgccggt aatgtctgcc 1260gcatgtgcgg ttttaaaaga ttttggcgtt ccatttgaag tgacaatagt ctctgctcat 1320agaactccac ataggatgtc agcatatgct atttccgcaa gcaagcgtgg aattaaaaca 1380attatcgctg gagctggtgg ggctgctcac ttgccaggta tggtggctgc aatgacacca 1440cttcctgtca tcggtgtgcc cgtaaaaggt tcttgtctag atggagtaga ttctttacat 1500tcaattgtgc aaatgcctag aggtgttcca gtagctaccg tcgctattaa taatagtacg 1560aacgctgcgc tgttggctgt cagactgctt ggcgcttatg attcaagtta tacaacgaaa 1620atggaacagt ttttattaaa gcaagaagaa gaagttcttg tcaaagcaca aaagttagaa 1680actgtcggtt acgaagctta tctagaaaac aagtaa 1716434179DNASaccharomyces cerevisiae 43atgactaacg aaaaggtctg gatagagaag ttggataatc caactctttc agtgttacca 60catgactttt tacgcccaca acaagaacct tatacgaaac aagctacata ttcgttacag 120ctacctcagc tcgatgtgcc tcatgatagt ttttctaaca aatacgctgt cgctttgagt 180gtatgggctg cattgatata tagagtaacc ggtgacgatg atattgttct ttatattgcg 240aataacaaaa tcttaagatt caatattcaa ccaacgtggt catttaatga gctgtattct 300acaattaaca atgagttgaa caagctcaat

tctattgagg ccaatttttc ctttgacgag 360ctagctgaaa aaattcaaag ttgccaagat ctggaaagga cccctcagtt gttccgtttg 420gcctttttgg aaaaccaaga tttcaaatta gacgagttca agcatcattt agtggacttt 480gctttgaatt tggataccag taataatgcg catgttttga acttaattta taacagctta 540ctgtattcga atgaaagagt aaccattgtt gcggaccaat ttactcaata tttgactgct 600gcgctaagcg atccatccaa ttgcataact aaaatctctc tgatcaccgc atcatccaag 660gatagtttac ctgatccaac taagaacttg ggctggtgcg atttcgtggg gtgtattcac 720gacattttcc aggacaatgc tgaagccttc ccagagagaa cctgtgttgt ggagactcca 780acactaaatt ccgacaagtc ccgttctttc acttatcgcg acatcaaccg cacttctaac 840atagttgccc attatttgat taaaacaggt atcaaaagag gtgatgtagt gatgatctat 900tcttctaggg gtgtggattt gatggtatgt gtgatgggtg tcttgaaagc cggcgcaacc 960ttttcagtta tcgaccctgc atatccccca gccagacaaa ccatttactt aggtgttgct 1020aaaccacgtg ggttgattgt tattagagct gctggacaat tggatcaact agtagaagat 1080tacatcaatg atgaattgga gattgtttca agaatcaatt ccatcgctat tcaagaaaat 1140ggtaccattg aaggtggcaa attggacaat ggcgaggatg ttttggctcc atatgatcac 1200tacaaagaca ccagaacagg tgttgtagtt ggaccagatt ccaacccaac cctatctttc 1260acatctggtt ccgaaggtat tcctaagggt gttcttggta gacatttttc cttggcttat 1320tatttcaatt ggatgtccaa aaggttcaac ttaacagaaa atgataaatt cacaatgctg 1380agcggtattg cacatgatcc aattcaaaga gatatgttta caccattatt tttaggtgcc 1440caattgtatg tccctactca agatgatatt ggtacaccgg gccgtttagc ggaatggatg 1500agtaagtatg gttgcacagt tacccattta acacctgcca tgggtcaatt acttactgcc 1560caagctacta caccattccc taagttacat catgcgttct ttgtgggtga cattttaaca 1620aaacgtgatt gtctgaggtt acaaaccttg gcagaaaatt gccgtattgt taatatgtac 1680ggtaccactg aaacacagcg tgcagtttct tatttcgaag ttaaatcaaa aaatgacgat 1740ccaaactttt tgaaaaaatt gaaagatgtc atgcctgctg gtaaaggtat gttgaacgtt 1800cagctactag ttgttaacag gaacgatcgt actcaaatat gtggtattgg cgaaataggt 1860gagatttatg ttcgtgcagg tggtttggcc gaaggttata gaggattacc agaattgaat 1920aaagaaaaat ttgtgaacaa ctggtttgtt gaaaaagatc actggaatta tttggataag 1980gataatggtg aaccttggag acaattctgg ttaggtccaa gagatagatt gtacagaacg 2040ggtgatttag gtcgttatct accaaacggt gactgtgaat gttgcggtag ggctgatgat 2100caagttaaaa ttcgtgggtt cagaatcgaa ttaggagaaa tagatacgca catttcccaa 2160catccattgg taagagaaaa cattacttta gttcgcaaaa atgccgacaa tgagccaaca 2220ttgatcacat ttatggtccc aagatttgac aagccagatg acttgtctaa gttccaaagt 2280gatgttccaa aggaggttga aactgaccct atagttaagg gcttaatcgg ttaccatctt 2340ttatccaagg acatcaggac tttcttaaag aaaagattgg ctagctatgc tatgccttcc 2400ttgattgtgg ttatggataa actaccattg aatccaaatg gtaaagttga taagcctaaa 2460cttcaattcc caactcccaa gcaattaaat ttggtagctg aaaatacagt ttctgaaact 2520gacgactctc agtttaccaa tgttgagcgc gaggttagag acttatggtt aagtatatta 2580cctaccaagc cagcatctgt atcaccagat gattcgtttt tcgatttagg tggtcattct 2640atcttggcta ccaaaatgat ttttacctta aagaaaaagc tgcaagttga tttaccattg 2700ggcacaattt tcaagtatcc aacgataaag gcctttgccg cggaaattga cagaattaaa 2760tcatcgggtg gatcatctca aggtgaggtc gtcgaaaatg tcactgcaaa ttatgcggaa 2820gacgccaaga aattggttga gacgctacca agttcgtacc cctctcgaga atattttgtt 2880gaacctaata gtgccgaagg aaaaacaaca attaatgtgt ttgttaccgg tgtcacagga 2940tttctgggct cctacatcct tgcagatttg ttaggacgtt ctccaaagaa ctacagtttc 3000aaagtgtttg cccacgtcag ggccaaggat gaagaagctg catttgcaag attacaaaag 3060gcaggtatca cctatggtac ttggaacgaa aaatttgcct caaatattaa agttgtatta 3120ggcgatttat ctaaaagcca atttggtctt tcagatgaga agtggatgga tttggcaaac 3180acagttgata taattatcca taatggtgcg ttagttcact gggtttatcc atatgccaaa 3240ttgagggatc caaatgttat ttcaactatc aatgttatga gcttagccgc cgtcggcaag 3300ccaaagttct ttgactttgt ttcctccact tctactcttg acactgaata ctactttaat 3360ttgtcagata aacttgttag cgaagggaag ccaggcattt tagaatcaga cgatttaatg 3420aactctgcaa gcgggctcac tggtggatat ggtcagtcca aatgggctgc tgagtacatc 3480attagacgtg caggtgaaag gggcctacgt gggtgtattg tcagaccagg ttacgtaaca 3540ggtgcctctg ccaatggttc ttcaaacaca gatgatttct tattgagatt tttgaaaggt 3600tcagtccaat taggtaagat tccagatatc gaaaattccg tgaatatggt tccagtagat 3660catgttgctc gtgttgttgt tgctacgtct ttgaatcctc ccaaagaaaa tgaattggcc 3720gttgctcaag taacgggtca cccaagaata ttattcaaag actacttgta tactttacac 3780gattatggtt acgatgtcga aatcgaaagc tattctaaat ggaagaaatc attggaggcg 3840tctgttattg acaggaatga agaaaatgcg ttgtatcctt tgctacacat ggtcttagac 3900aacttacctg aaagtaccaa agctccggaa ctagacgata ggaacgccgt ggcatcttta 3960aagaaagaca ccgcatggac aggtgttgat tggtctaatg gaataggtgt tactccagaa 4020gaggttggta tatatattgc atttttaaac aaggttggat ttttacctcc accaactcat 4080aatgacaaac ttccactgcc aagtatagaa ctaactcaag cgcaaataag tctagttgct 4140tcaggtgctg gtgctcgtgg aagctccgca gcagcttaa 417944675DNASaccharomyces cerevisiae 44atgtctgtta ttaatttcac aggtagttct ggtccattgg tgaaagtttg cggcttgcag 60agcacagagg ccgcagaatg tgctctagat tccgatgctg acttgctggg tattatatgt 120gtgcccaata gaaagagaac aattgacccg gttattgcaa ggaaaatttc aagtcttgta 180aaagcatata aaaatagttc aggcactccg aaatacttgg ttggcgtgtt tcgtaatcaa 240cctaaggagg atgttttggc tctggtcaat gattacggca ttgatatcgt ccaactgcat 300ggagatgagt cgtggcaaga ataccaagag ttcctcggtt tgccagttat taaaagactc 360gtatttccaa aagactgcaa catactactc agtgcagctt cacagaaacc tcattcgttt 420attcccttgt ttgattcaga agcaggtggg acaggtgaac ttttggattg gaactcgatt 480tctgactggg ttggaaggca agagagcccc gaaagcttac attttatgtt agctggtgga 540ctgacgccag aaaatgttgg tgatgcgctt agattaaatg gcgttattgg tgttgatgta 600agcggaggtg tggagacaaa tggtgtaaaa gactctaaca aaatagcaaa tttcgtcaaa 660aatgctaaga aatag 675451095DNASaccharomyces cerevisiae 45atgtctgccc ctaagaagat cgtcgttttg ccaggtgacc acgttggtca agaaatcaca 60gccgaagcca ttaaggttct taaagctatt tctgatgttc gttccaatgt caagttcgat 120ttcgaaaatc atttaattgg tggtgctgct atcgatgcta caggtgttcc acttccagat 180gaggcgctgg aagcctccaa gaaggctgat gccgttttgt taggtgctgt gggtggtcct 240aaatggggta ccggtagtgt tagacctgaa caaggtttac taaaaatccg taaagaactt 300caattgtacg ccaacttaag accatgtaac tttgcatccg actctctttt agacttatct 360ccaatcaagc cacaatttgc taaaggtact gacttcgttg ttgtcagaga attagtggga 420ggtatttact ttggtaagag aaaggaagac gatggtgatg gtgtcgcttg ggatagtgaa 480caatacaccg ttccagaagt gcaaagaatc acaagaatgg ccgctttcat ggccctacaa 540catgagccac cattgcctat ttggtccttg gataaagcta atgttttggc ctcttcaaga 600ttatggagaa aaactgtgga ggaaaccatc aagaacgaat tccctacatt gaaggttcaa 660catcaattga ttgattctgc cgccatgatc ctagttaaga acccaaccca cctaaatggt 720attataatca ccagcaacat gtttggtgat atcatctccg atgaagcctc cgttatccca 780ggttccttgg gtttgttgcc atctgcgtcc ttggcctctt tgccagacaa gaacaccgca 840tttggtttgt acgaaccatg ccacggttct gctccagatt tgccaaagaa taaggtcaac 900cctatcgcca ctatcttgtc tgctgcaatg atgttgaaat tgtcattgaa cttgcctgaa 960gaaggtaagg ccattgaaga tgcagttaaa aaggttttgg atgcaggtat cagaactggt 1020gatttaggtg gttccaacag taccaccgaa gtcggtgatg ctgtcgccga agaagttaag 1080aaaatccttg cttaa 109546804DNASaccharomyces cerevisiae 46atgtcgaaag ctacatataa ggaacgtgct gctactcatc ctagtcctgt tgctgccaag 60ctatttaata tcatgcacga aaagcaaaca aacttgtgtg cttcattgga tgttcgtacc 120accaaggaat tactggagtt agttgaagca ttaggtccca aaatttgttt actaaaaaca 180catgtggata tcttgactga tttttccatg gagggcacag ttaagccgct aaaggcatta 240tccgccaagt acaatttttt actcttcgaa gacagaaaat ttgctgacat tggtaataca 300gtcaaattgc agtactctgc gggtgtatac agaatagcag aatgggcaga cattacgaat 360gcacacggtg tggtgggccc aggtattgtt agcggtttga agcaggcggc ggaagaagta 420acaaaggaac ctagaggcct tttgatgtta gcagaattgt catgcaaggg ctccctagct 480actggagaat atactaaggg tactgttgac attgcgaaga gcgacaaaga ttttgttatc 540ggctttattg ctcaaagaga catgggtgga agagatgaag gttacgattg gttgattatg 600acacccggtg tgggtttaga tgacaaggga gacgcattgg gtcaacagta tagaaccgtg 660gatgatgtgg tctctacagg atctgacatt attattgttg gaagaggact atttgcaaag 720ggaagggatg ctaaggtaga gggtgaacgt tacagaaaag caggctggga agcatatttg 780agaagatgcg gccagcaaaa ctaa 80447663DNASaccharomyces cerevisiae 47atgacagagc agaaagccct agtaaagcgt attacaaatg aaaccaagat tcagattgcg 60atctctttaa agggtggtcc cctagcgata gagcactcga tcttcccaga aaaagaggca 120gaagcagtag cagaacaggc cacacaatcg caagtgatta acgtccacac aggtataggg 180tttctggacc atatgataca tgctctggcc aagcattccg gctggtcgct aatcgttgag 240tgcattggtg acttacacat agacgaccat cacaccactg aagactgcgg gattgctctc 300ggtcaagctt ttaaagaggc cctaggggcc gtgcgtggag taaaaaggtt tggatcagga 360tttgcgcctt tggatgaggc actttccaga gcggtggtag atctttcgaa caggccgtac 420gcagttgtcg aacttggttt gcaaagggag aaagtaggag atctctcttg cgagatgatc 480ccgcattttc ttgaaagctt tgcagaggct agcagaatta ccctccacgt tgattgtctg 540cgaggcaaga atgatcatca ccgtagtgag agtgcgttca aggctcttgc ggttgccata 600agagaagcca cctcgcccaa tggtaccaac gatgttccct ccaccaaagg tgttcttatg 660tag 66348736DNAAequorea victoria 48aagctttatt aaaatgtcta aaggtgaaga attattcact ggtgttgtcc caattttggt 60tgaattagat ggtgatgtta atggtcacaa attttctgtc tccggtgaag gtgaaggtga 120tgctacttac ggtaaattga ccttaaaatt tatttgtact actggtaaat tgccagttcc 180atggccaacc ttagtcacta ctttcggtta tggtgttcaa tgttttgcta gatacccaga 240tcatatgaaa caacatgact ttttcaagtc tgccatgcca gaaggttatg ttcaagaaag 300aactattttt ttcaaagatg acggtaacta caagaccaga gctgaagtca agtttgaagg 360tgatacctta gttaatagaa tcgaattaaa aggtattgat tttaaagaag atggtaacat 420tttaggtcac aaattggaat acaactataa ctctcacaat gtttacatca tggctgacaa 480acaaaagaat ggtatcaaag ttaacttcaa aattagacac aacattgaag atggttctgt 540tcaattagct gaccattatc aacaaaatac tccaattggt gatggtccag tcttgttacc 600agacaaccat tacttatcca ctcaatctgc cttatccaaa gatccaaacg aaaagagaga 660ccacatggtc ttgttagaat ttgttactgc tgctggtatt acccatggta tggatgaatt 720gtacaaataa ctgcag 73649945DNARenilla reniformis 49atggcttcga aagtttatga tccagaacaa aggaaacgga tgataactgg tccgcagtgg 60tgggccagat gtaaacaaat gaatgttctt gattcattta ttaattatta tgattcagaa 120aaacatgcag aaaatgctgt tattttttta catggtaacg cggcctcttc ttatttatgg 180cgacatgttg tgccacatat tgagccagta gcgcggtgta ttataccaga ccttattggt 240atgggcaaat caggcaaatc tggtaatggt tcttataggt tacttgatca ttacaaatat 300cttactgcat ggtttgaact tcttaattta ccaaagaaga tcatttttgt cggccatgat 360tggggtgctt gtttggcatt tcattatagc tatgagcatc aagataagat caaagcaata 420gttcacgctg aaagtgtagt agatgtgatt gaatcatggg atgaatggcc tgatattgaa 480gaagatattg cgttgatcaa atctgaagaa ggagaaaaaa tggttttgga gaataacttc 540ttcgtggaaa ccatgttgcc atcaaaaatc atgagaaagt tagaaccaga agaatttgca 600gcatatcttg aaccattcaa agagaaaggt gaagttcgtc gtccaacatt atcatggcct 660cgtgaaatcc cgttagtaaa aggtggtaaa cctgacgttg tacaaattgt taggaattat 720aatgcttatc tacgtgcaag tgatgattta ccaaaaatgt ttattgaatc ggacccagga 780ttcttttcca atgctattgt tgaaggtgcc aagaagtttc ctaatactga atttgtcaaa 840gtaaaaggtc ttcatttttc gcaagaagat gcacctgatg aaatgggaaa atatatcaaa 900tcgttcgttg agcgagttct caaaaatgaa caaagatcta tctag 945502387DNAPhotinus pyralis 50ctgcagaaat aactaggtac taagcccgtt tgtgaaaagt ggccaaaccc ataaatttgg 60caattacaat aaagaagcta aaattgtggt caaactcaca aacattttta ttatatacat 120tttagtagct gatgcttata aaagcaatat ttaaatcgta aacaacaaat aaaataaaat 180ttaaacgatg tgattaagag ccaaaggtcc tctagaaaaa ggtatttaag caacggaatt 240cctttgtgtt acattcttga atgtcgctcg cagtgacatt agcattccgg tactgttggt 300aaaatggaag acgccaaaaa cataaagaaa ggcccggcgc cattctatcc tctagaggat 360ggaaccgctg gagagcaact gcataaggct atgaagagat acgccctggt tcctggaaca 420attgcttttg tgagtatttc tgtctgattt ctttcgagtt aacgaaatgt tcttatgttt 480ctttagacag atgcacatat cgaggtgaac atcacgtacg cggaatactt cgaaatgtcc 540gttcggttgg cagaagctat gaaacgatat gggctgaata caaatcacag aatcgtcgta 600tgcagtgaaa actctcttca attctttatg ccggtgttgg gcgcgttatt tatcggagtt 660gcagttgcgc ccgcgaacga catttataat gaacgtaagc accctcgcca tcagaccaaa 720gggaatgacg tatttaattt ttaaggtgaa ttgctcaaca gtatgaacat ttcgcagcct 780accgtagtgt ttgtttccaa aaaggggttg caaaaaattt tgaacgtgca aaaaaaatta 840ccaataatcc agaaaattat tatcatggat tctaaaacgg attaccaggg atttcagtcg 900atgtacacgt tcgtcacatc tcatctacct cccggtttta atgaatacga ttttgtacca 960gagtcctttg atcgtgacaa aacaattgca ctgataatga attcctctgg atctactggg 1020ttacctaagg gtgtggccct tccgcataga actgcctgcg tcagattctc gcatgccagg 1080tatgtcgtat aacaagagat taagtaatgt tgctacacac attgtagaga tcctattttt 1140ggcaatcaaa tcattccgga tactgcgatt ttaagtgttg ttccattcca tcacggtttt 1200ggaatgttta ctacactcgg atatttgata tgtggatttc gagtcgtctt aatgtataga 1260tttgaagaag agctgttttt acgatccctt caggattaca aaattcaaag tgcgttgcta 1320gtaccaaccc tattttcatt cttcgccaaa agcactctga ttgacaaata cgatttatct 1380aatttacacg aaattgcttc tgggggcgca cctctttcga aagaagtcgg ggaagcggtt 1440gcaaaacggt gagttaagcg cattgctagt atttcaaggc tctaaaacgg cgcgtagctt 1500ccatcttcca gggatacgac aaggatatgg gctcactgag actacatcag ctattctgat 1560tacacccgag ggggatgata aaccgggcgc ggtcggtaaa gttgttccat tttttgaagc 1620gaaggttgtg gatctggata ccgggaaaac gctgggcgtt aatcagagag gcgaattatg 1680tgtcagagga cctatgatta tgtccggtta tgtaaacaat ccggaagcga ccaacgcctt 1740gattgacaag gatggatggc tacattctgg agacatagct tactgggacg aagacgaaca 1800cttcttcata gttgaccgct tgaagtcttt aattaaatac aaaggatatc aggtaatgaa 1860gatttttaca tgcacacacg ctacaatacc tgtaggtggc ccccgctgaa ttggaatcga 1920tattgttaca acaccccaac atcttcgacg cgggcgtggc aggtcttccc gacgatgacg 1980ccggtgaact tcccgccgcc gttgttgttt tggagcacgg aaagacgatg acggaaaaag 2040agatcgtgga ttacgtcgcc agtaaatgaa ttcgttttac gttactcgta ctacaattct 2100tttcataggt caagtaacaa ccgcgaaaaa gttgcgcgga ggagttgtgt ttgtggacga 2160agtaccgaaa ggtcttaccg gaaaactcga cgcaagaaaa atcagagaga tcctcataaa 2220ggccaagaag ggcggaaagt ccaaattgta aaatgtaact gtattcagcg atgacgaaat 2280tcttagctat tgtaatatta tatgcaaatt gatgaatggt aattttgtaa ttgtgggtca 2340ctgtactatt ttaacgaata ataaaatcag gtataggtaa ctaaaaa 2387513075DNAEscherichia coli 51atgaccatga ttacggattc actggccgtc gttttacaac gtcgtgactg ggaaaaccct 60ggcgttaccc aacttaatcg ccttgcagca catccccctt tcgccagctg gcgtaatagc 120gaagaggccc gcaccgatcg cccttcccaa cagttgcgca gcctgaatgg cgaatggcgc 180tttgcctggt ttccggcacc agaagcggtg ccggaaagct ggctggagtg cgatcttcct 240gaggccgata ctgtcgtcgt cccctcaaac tggcagatgc acggttacga tgcgcccatc 300tacaccaacg tgacctatcc cattacggtc aatccgccgt ttgttcccac ggagaatccg 360acgggttgtt actcgctcac atttaatgtt gatgaaagct ggctacagga aggccagacg 420cgaattattt ttgatggcgt taactcggcg tttcatctgt ggtgcaacgg gcgctgggtc 480ggttacggcc aggacagtcg tttgccgtct gaatttgacc tgagcgcatt tttacgcgcc 540ggagaaaacc gcctcgcggt gatggtgctg cgctggagtg acggcagtta tctggaagat 600caggatatgt ggcggatgag cggcattttc cgtgacgtct cgttgctgca taaaccgact 660acacaaatca gcgatttcca tgttgccact cgctttaatg atgatttcag ccgcgctgta 720ctggaggctg aagttcagat gtgcggcgag ttgcgtgact acctacgggt aacagtttct 780ttatggcagg gtgaaacgca ggtcgccagc ggcaccgcgc ctttcggcgg tgaaattatc 840gatgagcgtg gtggttatgc cgatcgcgtc acactacgtc tgaacgtcga aaacccgaaa 900ctgtggagcg ccgaaatccc gaatctctat cgtgcggtgg ttgaactgca caccgccgac 960ggcacgctga ttgaagcaga agcctgcgat gtcggtttcc gcgaggtgcg gattgaaaat 1020ggtctgctgc tgctgaacgg caagccgttg ctgattcgag gcgttaaccg tcacgagcat 1080catcctctgc atggtcaggt catggatgag cagacgatgg tgcaggatat cctgctgatg 1140aagcagaaca actttaacgc cgtgcgctgt tcgcattatc cgaaccatcc gctgtggtac 1200acgctgtgcg accgctacgg cctgtatgtg gtggatgaag ccaatattga aacccacggc 1260atggtgccaa tgaatcgtct gaccgatgat ccgcgctggc taccggcgat gagcgaacgc 1320gtaacgcgaa tggtgcagcg cgatcgtaat cacccgagtg tgatcatctg gtcgctgggg 1380aatgaatcag gccacggcgc taatcacgac gcgctgtatc gctggatcaa atctgtcgat 1440ccttcccgcc cggtgcagta tgaaggcggc ggagccgaca ccacggccac cgatattatt 1500tgcccgatgt acgcgcgcgt ggatgaagac cagcccttcc cggctgtgcc gaaatggtcc 1560atcaaaaaat ggctttcgct acctggagag acgcgcccgc tgatcctttg cgaatacgcc 1620cacgcgatgg gtaacagtct tggcggtttc gctaaatact ggcaggcgtt tcgtcagtat 1680ccccgtttac agggcggctt cgtctgggac tgggtggatc agtcgctgat taaatatgat 1740gaaaacggca acccgtggtc ggcttacggc ggtgattttg gcgatacgcc gaacgatcgc 1800cagttctgta tgaacggtct ggtctttgcc gaccgcacgc cgcatccagc gctgacggaa 1860gcaaaacacc agcagcagtt tttccagttc cgtttatccg ggcaaaccat cgaagtgacc 1920agcgaatacc tgttccgtca tagcgataac gagctcctgc actggatggt ggcgctggat 1980ggtaagccgc tggcaagcgg tgaagtgcct ctggatgtcg ctccacaagg taaacagttg 2040attgaactgc ctgaactacc gcagccggag agcgccgggc aactctggct cacagtacgc 2100gtagtgcaac cgaacgcgac cgcatggtca gaagccgggc acatcagcgc ctggcagcag 2160tggcgtctgg cggaaaacct cagtgtgacg ctccccgccg cgtcccacgc catcccgcat 2220ctgaccacca gcgaaatgga tttttgcatc gagctgggta ataagcgttg gcaatttaac 2280cgccagtcag gctttctttc acagatgtgg attggcgata aaaaacaact gctgacgccg 2340ctgcgcgatc agttcacccg tgcaccgctg gataacgaca ttggcgtaag tgaagcgacc 2400cgcattgacc ctaacgcctg ggtcgaacgc tggaaggcgg cgggccatta ccaggccgaa 2460gcagcgttgt tgcagtgcac ggcagataca cttgctgatg cggtgctgat tacgaccgct 2520cacgcgtggc agcatcaggg gaaaacctta tttatcagcc ggaaaaccta ccggattgat 2580ggtagtggtc aaatggcgat taccgttgat gttgaagtgg cgagcgatac accgcatccg 2640gcgcggattg gcctgaactg ccagctggcg caggtagcag agcgggtaaa ctggctcgga 2700ttagggccgc aagaaaacta tcccgaccgc cttactgccg cctgttttga ccgctgggat 2760ctgccattgt cagacatgta taccccgtac gtcttcccga gcgaaaacgg tctgcgctgc 2820gggacgcgcg aattgaatta tggcccacac cagtggcgcg gcgacttcca gttcaacatc 2880agccgctaca gtcaacagca actgatggaa accagccatc gccatctgct gcacgcggaa 2940gaaggcacat ggctgaatat cgacggtttc catatgggga ttggtggcga cgactcctgg 3000agcccgtcag tatcggcgga attccagctg agcgccggtc gctaccatta ccagttggtc 3060tggtgtcaaa aataa 3075521003DNASaccharomyces cerevisiae 52tctaaatatc gtcccgttac cctcatcgct actgccgggc gttcccaacc ccttccgagg 60cagattatat ttatttatct ttttaacaat ttgtccctat ataggcgggc cgaacacagc 120acgtgaaaga actctcaggc ttccacaaca ggccatatca agtccacact tccctcatta 180ctagcatttt tacacaagca gtccacgcat tccgcaacag tgttcacctt tcttttccct

240aacttatctt attatttgtt tgttgatcgc aaacagaccc ttttttttgg tgagcgcatt 300ttacacagtc tcaagtgtcc tctactataa aaatacaacc tcaaacagta cttactggcg 360tccgcagaat attactgcac tctcaatctg taaagaatat aacaagtgac ccattccctt 420gttttattca acttcgaaat ctctctggct atctttgcat gcttatctaa ctttcacgtg 480acccggatat tgttctctgc tcaaaaaaga actgcaaaga aggaaataga aaaatagcat 540acaggctcaa agctatagtt ttctgaaaag ggacaccacg aatacagtag tatcaaagag 600aaaaaagact tctttatact tacagaaggt tcattttctg attctactct tccaatctag 660tgtcgcaaaa aaacaaaact tactggtatt agctggcaaa aaaaaaaaga ataggttata 720attaaagaca tcttttctct ataaattttt tcttagaaga aaaagccaaa aaaaaaaaac 780ctgcttcata cccgccatca aatcttatag gccttataga ctgcatatta ccggattctt 840tctctccgtt aaccctacta ttctttcact atactttaac ctaaaataaa aaaggaaaaa 900aaaaattaaa aacttccaaa aacttagaaa tttcaaatac aaaacaaaaa gacacgtaaa 960gttagtgcaa tatttttttc ttacaatttt ttgaaactcg atg 1003531003DNASaccharomyces cerevisiae 53agaacattat gaagtaaaag gacaatcagc acgccttcca gacttttaag aaacattgat 60ggagccattg atatcggcac cgtacctaac aacaacaaaa atgtctgctc ctgctacgct 120tgatgctgcc tgtatttttt gcaagattat taaaagtatg tcacattact aataaagagc 180ttacactcac accaatgatg gcgatagtct ctatgtagta catatacata aagcagaata 240ctaacaatcg atccgctatg caacaggcga aattccatcc ttcaaattga ttgaaacaaa 300gtactcgtat gctttcttgg acatccaacc tactgctgaa ggtcatgctt taatcattcc 360taagtaccat ggtgcgaagt tgcatgacat cccggacgaa ttccttaccg atgctatgcc 420gattgccaag agactggcca aggcaatgaa gttggacact tataatgtgt tgcagaataa 480tggtaaaatt gcgcatcaag aagtcgacca cgtccacttc catttgattc ctaagagaga 540tgagaaaagt ggtttgattg tagggtggcc agcccaagaa acggacttcg ataagttggg 600caagctacac aaggaattgc ttgccaaact agaaggctcc gattagagta atgcatgcta 660tgatttcttt tagcgttttc ttttcatatt taagtttata catatgggtg tgtttgcttc 720cattcatatc cactctataa tgctaacaat catgttacta gccatcgttg ctatcgatac 780cttatgaaca gctctaactc cttccttttt aacctaccgc cttttgcgca ctacccggca 840acccctcgaa tgtgaattcg gtggcaaaaa aggacatata tcagggccgt gtatttaaga 900gatccgcagt tgatgtagtc aattaatcta gttctattaa gatttgactc aacgccattg 960actcgataac tggctcaact acaagacaga tatacaaatc atg 1003541003DNASaccharomyces cerevisiae 54cgaactatag ggagattggt cctcaacaat atatttcttc cttgtcgacc cattaggtgt 60atgggcgagt tgctgcaggg aagacaacga atccctagaa gcgcacttgt aaagatcttg 120ctcttgtaag tagcgatgac ggtcatgaag atgaaagggt gcggttgaag tcaagttgaa 180cgtgatcgga tactgatttc tagaaacagg gggggctggt gttggttctg gcgaagccgc 240ttgctccgac tgctttgatg tcacagcttt gggtttctcc gctacactgt ctaccttagg 300attattgatc atgactcaag cttgcgatat gtgttggtgt catgcacaag acgccacaaa 360tgatagaaca gaaaagaaag tgaactaatc ttccaagacg aagaaaacca aaatccggga 420tgagttgaaa gtcaaaaaga ctgtatatat aaatttcaac ttttgtagaa gatgcagaaa 480aagaaaatga tatggtatgc agaaaaagaa ataaaccgct attatcctcg cggtttgtca 540ttataacagg caattacact agagaaagcc gcacacctcc ctccgtttct tttgccctgc 600gagtttttcc ggaaaagaaa aaaaaaacga aaattaaaac ccgcctgccc cgcggggtgg 660gggaggggtc accggaacaa atcggataat ccctcgcctg ccttagatat cgttctgaac 720ggctgaaatt atgaaagaag aagaacatca ctttacacgg atcgcacgcc cataattctt 780tttttttttt ttttcatatc ttcgacgttt gccactgcct tctctttttc tttctttttt 840ggcggccggt ggccaaacgc gccaaaaccg aaacgcttat aaaatgtagt tgccttgctc 900tttcattcga tatacatata agaacgctca ctgttatctt acattagaag ctagaaacta 960taacagtata acacagcaca agagaaccga gcagcccgcc atg 1003551003DNASaccharomyces cerevisiae 55agtaaaaaga atagtaatta ttacaatgga gaagataaga taaagttagc ggcaacaaat 60aaagaactca tcagagttct tggcttctct atgagtgaaa gtgtttcaaa ggtgtttttt 120tatgagacaa cagtaattcc cctccttcag aacagagtgt agtgattggc agtgaagcta 180tccctctttg ccacccaatt ttgacggcag ttctcatagc atctcaaagc aatagcagtg 240caaaagtaca taaccgtagg aaggtacgcg gtaggtattt gagttcgttg gtggttatcc 300tccgcaaggc gcttcggcgg ttatttgttg atagtcgaag aacaccaaaa aaaatgctgt 360tattgctttc tccgtaaaca ataaaacccg gtagcgggat aacgcggctg atgcttttat 420ttaggaagga atacttacat tatcatgaga acattgtcaa gggcattctg atacgggcct 480tccatcgcaa gaaaaaggca gcaacggact gagggacgga gagagttacg gcataagaag 540tagtaggaga gcagagtgtc ataaagttat attattctcg tcctaaagtc aattagttct 600gttgcgcttg acaatatatg tcgtgtaata ccgtccctta gcagaagaaa gaaagacgga 660tccatatatg ttaaaatgct tcagagatgt ttctttaatg tgccgtccaa caaaggtatc 720ttctgtagct tcctctattt tcgatcagat ctcatagtga gaaggcgcaa ttcagtagtt 780aaaagcgggg aacagtgtga atccggagac ggcaagattg cccggccctt tttgcggaaa 840agataaaaca agatatattg cactttttcc accaagaaaa acaggaagtg gattaaaaaa 900tcaacaaagt ataacgccta ttgtcccaat aagcgtcggt tgttcttctt tattatttta 960ccaagtacgc tcgagggtac attctaatgc attaaaagac atg 1003561003DNASaccharomyces cerevisiae 56ataattgcgt ttaaacgcct ttccttttct tcatccattt tcctggtatt tatctcatcg 60tctctcttaa ttcttaattt actaccttca tctgggatta tgaactgtgg atgttccata 120tcacattcat ccttccctaa aggacaaaat ccggtcatgt atctttgaca gaaaaccttc 180ttaatatgcc gtctaggaca agaactcccc agaggacaga atcccatttc gtaattttca 240cattttggta tcttgctagc gggatctatg tgtagatatt gacaatctgg actttgtgta 300cagtacccgt ttttgctgaa gaagacacat tcaggcattt ttcgaagatt gtattcatgt 360aagtattcac attggtcatt ctttttgcac aaccctcgaa gccaatgtct acaaacaatt 420ttattctgaa atattggtaa cacatgcttt tttggacata acggtcccct cggacatgat 480ttagggcctt ctctagaatt gtaaaattca caaataggtc tgtcaggatc gagtgaaaac 540gaatactctt gcctgaggaa aggttcaaat ttaaaaggat attttgctgt atcggggtga 600attaggctca ttacataaac ttattgattt tattcgtcct agaatacttg tttaagatac 660agtgcagaaa tctttagctt ataattcaga aatgtgatat tttgaagcga ttggaacaac 720aaagtacagt gcattctata taattattaa aagttatagt ggactattgt aataacactt 780gttttcccca tatcataacc gacggcgcgt aaatgcatgc tcaatcaagt ttccgaataa 840gttaagtttg ccacccattg aggattaata tacacaaggc agcattgaaa aacctaattg 900ttaacactac acaaatctct attgttgtag taaactgcgc tttttaccac tgttacaata 960gttactaata cacgcaaaaa ttctggataa acacggcaaa atg 1003571003DNASaccharomyces cerevisiae 57gcacgtgaat gtgatgtctt gtgatggcgg gtgaattagg accggggtcc gctgagtgtt 60gaacttcaca aagcatatat cattgacata atcagaaacg tgcttgatca attgtgctat 120ggggaggtcc cggtgcaaga ttccaatcat ccttttgttc gtgtcacctt tgttctgtgc 180catcaacgac aaatagtgcg tcacaagcag cttcatcgtg attctctcct tcaggtggaa 240gttcaagaac tgcgaaattt gaaactttgg gtaacacgat tggatttcct gaagaccttt 300tgccaatacc acaatggcgt cctcgtggtc gtccagcagt tctgtgaact tggcctgtat 360cttgggagga ttgtgcaact cgtacgggta tgcgattgat agcaacgttt gcaagctttt 420caaatacaaa gagttggttc tctcaatatg agggttgatt accgcattat acggtagcct 480ctgaatggca ttaagccgtt tacacgtcaa tgaaagcaac aggttgattg tcttgatcgt 540cagcatgtac tcctccttct tggtcagcgg cggcctgtat tgcaggaaat actcgtagtt 600taggggcgca attggtttac tagcgtagtc ctgtatcagc agctcaatgt tcgacctaat 660cttgtaatgc tggtcgaacg acagttgcga cagcagctcg tgtgagggtc gctggcgatg 720tgcccagcgc attcccccac atttccatga acgcataatc ttccacatac taccgtgaag 780gcgtcttgat accacgtctt ccagttatgg tcttgactca ccaatgttct cagtttaatg 840ttgtttgctt catactggca gacattttcc cttattaccg tgagaagcga gcggtggatt 900aatcgggatg tcaaaaacaa gaaaattgca accttcttca cctataacct atatgatttg 960taggcagagg agtggaataa gcaacaaatc atagtcatca atg 1003581003DNASaccharomyces cerevisiae 58aaatctcact tcagaaacga aaaatactac atagatatca ccgaattgtt ccatgaggtc 60accttccaaa ccgaattggg ccaattgatg gacttaatca ctgcacctga agacaaagtc 120gacttgagta agttctccct aaagaagcac tccttcatag ttactttcaa gactgcttac 180tattctttct acttgcctgt cgcattggcc atgtacgttg ccggtatcac ggatgaaaag 240gatttgaaac aagccagaga tgtcttgatt ccattgggtg aatacttcca aattcaagat 300gactacttag actgcttcgg taccccagaa cagatcggta agatcggtac agatatccaa 360gataacaaat gttcttgggt aatcaacaag gcattggaac ttgcttccgc agaacaaaga 420aagactttag acgaaaatta cggtaagaag gactcagtcg cagaagccaa atgcaaaaag 480attttcaatg acttgaaaat tgaacagcta taccacgaat atgaagagtc tattgccaag 540gatttgaagg ccaaaatttc tcaggtcgat gagtctcgtg gcttcaaagc tgatgtctta 600actgcgttct tgaacaaagt ttacaagaga agcaaataga actaacgcta atcgataaaa 660cattagattt caaactagat aaggaccatg tataagaact atatacttcc aatataatat 720agtataagct ttaagatagt atctctcgat ctaccgttcc acgtgactag tccaaggatt 780ttttttaagc caatgaaaat gaagaaatgc gtgatcggaa attacgggta gtacgagaag 840gaaacttgag ccacccccca aattttattc atataataat aggaaaagca acgacctcat 900ctctcgaaca ttgtttactt gagcaagtcc gattaagagt aagttgtcgt acgttaaata 960caaataatca acaaaacact acacaaaaac ttctacgata atg 1003591003DNASaccharomyces cerevisiae 59aaaaaactga aatatagggt ttgttaatcc tggtaaaaat ctgatgtgac atcttctgta 60cttaggtggt cttaccatga agtcagcatc gatacaattg atgttatatt tcgttggttc 120caatatgtaa attgcctcga tggaggattg tccttttctt gttggggaat caatcaaatc 180aacagatgtg acattattta aaagttcttg gggtgtgagg aaaagataac tcaatattgt 240ctccacagtt ttatcgataa taagaaactt caagttattt ttcgtctcaa tctgattcaa 300aacccctatc aaatagttcc tctgtaattc aattaaatca gacatcgttc cgccaaacca 360agcatgtgca cactcttcta ctttgtcagt ggattctaat tattttcaag gtcttacaaa 420gcaatgtctt actagtttca atagggactt aaactgatcg tttaagcaaa agaaaaacac 480cgtgctgtgt gaccatctac caataattgc gagaacataa gacgacgccg ccattcacct 540ctctatcact tacaccatgt tatagggata agtgtgtagt cgatcggcta ttcgatgatt 600tttaaagagt gcctgtaata atagctgtat cgcaagtaag gaatacaaga ttactgatat 660tttgatccag gaggatggac atgttagata gaaaaactaa gagggctact acatccggtt 720tagtattctg ttattgggaa tgcttttccc aagacgcaag caagaggtga cacataaaca 780tagttttctt attgtatcgt tacatattct tattttacgc tgctgtcatt aaatatggca 840cttatctcag atacatttct tttaatcagc gaaaaaaatg gcgaggtgaa aaaaatcgat 900gagatgaaaa aattttttac tagtaaaggc gtattgatga tatattagca gctaaagtat 960agcaaggttt gtcaatttga agcagtccgc gtgttttaca atg 1003601003DNASaccharomyces cerevisiae 60ctaactataa taactggtag ctttgtcact cgtaccagga aaagtgaaga ttaaactgaa 60ttttaaaatg aacgatcgat tagttacgga agagcaagag ttgtttacaa aattgcgcga 120gattgtaggt tcaagtattc gcttttggga ggaacaactg ttttatcaag ttcaagatgt 180aagcaccata gaaaaccacg tcattctcag tttaaaatgt acaattttaa cggatgctca 240gataagtacg ttcataagca aacccagaga gcttcatacg catgccaaag gatatcctga 300aatctattac ctttccgagt tatcaacaac tgtcaatttt ttttctaaag agggaaacta 360tgtcgaaata agccaggtta ttcctcattt taatgaatat ttttcctctt taatagtgtc 420tcaattggaa tttgaatacc cgatggtctt ctccatgatt tcaaggctcc gattgaagtg 480gcaacaaagt tcgctcgctc cgatatccta cgccctaacg agcaattcag tacttcttcc 540aataatgctt aacatgattg cccaagacaa atcttcaaca accgcgtatc aaattctgtg 600tcgaagaaga ggtcctccaa ttcagaattt tcaaattttt tccttaccgg ctgtaacgta 660caataagtag catgcataaa atataattta atcaaatact tttgggcaat taaaatttta 720gttaacaata gttatgcaat gcgctttatg ttcatatgat accgtttata agctattgcc 780atatccttat cttattgctt ccagtagcct cgagtcgacc actaaaaaga tgtcacttaa 840gacggaaatt atgtagctgc acttcttttt taacaagttc ggtcggccct tcaagttctc 900ctttctaaag cctcattatt tattgcgtag atgctaaatg ttatcgcggt ttagcttgca 960tgttacgttt ccgttttaga acctggtcga gtagcgaata atg 1003611003DNASaccharomyces cerevisiae 61ttcgccaacc atcatacccg aatgtttcat tagcgaactg aatgagagca tgccctggta 60tcagcttaga taagttgtgc ttcccatatt tattattgtg gtaaatattg tacgtgtacc 120tttcgatctt ggactgtaga agcccaatcc tctgcaccga ccaagcgctg gcaggtcttc 180cattccaatc ttcgatgatt tggaactctt ttatatccaa gcccggtgct gtgccgtatg 240tagtcgaatc atacgatatg ctcgaactgg gcttcgcttg tatcgtcatt attttgtctg 300tttatcctga aatatgctct tctcctctac gtaacccttt aatggtccaa agcatgtgct 360aaactgccac agactccctc aatgatgttc ttatccttcc ttgccgttac tgcttcctat 420catatctgcc cttgccaaac tgtggcttcc tctaatcaat ttgccccagt acattgaaaa 480gcacgtgacg tgacaccaac ttgaaagaca ttagtgtcca acgcgatata atggtcaata 540aaatacccaa ttttatcaag tgaacatgat attattcaat actatagtac tttaaagaaa 600acttcaacaa gttgcttcat tgctatatta tacaattatg ggtgatgccg gtcggctaac 660ctttctttcg cagcgccaca tacaagaaca tatggtaatt actaagaact ttttggaaac 720tatttccatg aagaaaacaa aatttactgg cttctgtctt cgaagtaaat ttagcgaact 780tgatactttc gtttggacag tcgtttagat ttgcaactgt ctgttcttat ttcttgctat 840tattaccaga aataaagcct aaagcgcgtg gttcttacga aaaaaataga ccttgcacat 900taacagggtt tagacatcac agagactgaa tactggagag aagacaattc ttgttcacga 960cttcgagtga ttaatatcta taacaaccct cctatcaaga atg 1003621003DNASaccharomyces cerevisiae 62tgaaaggcaa atttacgctc ttcaagacac caatttagga ttggtggcta ccgcggagat 60acctttggca ggtctagggg caaacaaagt tctagagtta aactcgggag aatgttctaa 120gaaactagtt ggagtaagta gatgttacag agctgaggca ggtgccaggg gaaaagatac 180gaaaggtctc tatcgcgttc atgagtttac taaagtagaa ttattttgct ggagcaagcc 240agaaaccagt gcaaaggtcc ttgaggaaat aaagcaattt cagatttctg tagttgagga 300attaggaata ccggccaaag tactaaatat gccatcaaac gatcttggta atcccgcttt 360caagaaatac gacatcgaag cttggatgcc aggaaggggg aaatttggcg agataagtag 420tgcctccaat tgtaccgatt tccaaagtag aagattaaat acaaagtaca gggacgataa 480cacaggaaag ctagaatatg tgcacacgct gaatggcaca gcaatggcta tcccaagagt 540gatagtagca ctagtagaaa atttctatga cccaagcacc ggtaagatat ctgttcctga 600atgtttgagg gagtttatga atggccaacg atacatttaa taagtaagaa aatcttgtaa 660atatgtaatc ttatgttaac cgtagcatca ttgtgttgga cgaaatcctc tgtgatgttc 720tgtgtgattg aaattgtatg gtattttcga tcatacgagt atttttccta aagatgaaag 780agaactcgat tcctaaacag ttgtttgtag ggcataacgt tgtatcgtaa atacttacca 840tacgcttagg tatattcctt tagatttccg taacaccttt cagttttact attccgcgtg 900gcgaggtaaa gatcataaaa atacaagttt gttatagcat ttcctgcaaa taattgctgt 960aactagtggc gaaaaggtca tagaattatt cgcctaaatt atg 1003631003DNASaccharomyces cerevisiae 63ccggaagtaa ttttatcaat tatagtttcc aaatcatcat attcttgaac tatatcaatt 60aaatcatcac tcgtccagtc agggaacaat tctgtaagcg tatctatttt ggactttagc 120gcaggattta gttttttact actatgacta ttatgattag acttcctaaa ttgtgtagac 180attatatata tatgatgatg tagattatat tgagaaaacg accaaacaaa aataaatatg 240taagtacttt atgatggtga tttttttggg gtaattggta agagtttttc ttgtagcttc 300aaaagatcaa atataaaata cgaatgtttc tgaaattact gtaaaagact taggaaaagg 360aatgaaacgt ttatatggga gagaacgaaa atttttcctt ttcccgccac tactttttgc 420caccatttcc cgttatttat ttgggcgagt gctcacctcc gacggaatca cgggtgacgg 480atatcctaaa aaggtaaaga attgaaacag atctattaat atacggatca ctatacatta 540ttataagtcg atattgcagt attagtattt acatgttgaa taatgcacat tctgtgctaa 600aatatatact tcatttgtca acttctttta gtttgccgcc attttcaaac ggcgcctcct 660ccctagcttc gtctagagca ggcttaatac cttgtttgac gagagctgcg ttgacacatg 720tagtataagc gtaccattgt tttgagcact cgttctcaac ggattttccc ttcaggaatt 780tttcgctata ccattcatta aaacaactat cgtatttcgt cttcaggtca gtgcattcag 840gcgcaaaact agctgacatt atattcccca tataaaactg gtattattgt tattgtaatt 900caagttaaaa cacaaacaga tgttttctaa tgacctctcc cggcatatat ctggcgcact 960tagaataaat ttctacatgc aaatactctg aatattctga atg 1003641003DNASaccharomyces cerevisiae 64ttcttcttct ccattattat cttcagtagt tgtcttgtca tcagattgtc cctgttgcga 60tttttcatca tctgaatgtt ctggatcttt tttttcagaa gatccagcat tgttgtctag 120tgttttgtca ctagtatttt cttccgagtt ctcagaactt atgttttcat ccttttgatt 180gttagcggtg gcattgtctt cattggattg ctcatcatct ttggttgata cctttgattc 240atcagtatct ttatcttcgg aagacttgtt gtcttcttct gctagaacaa ccaattcacc 300atcttcagct acttttgaag caccaatttt atcaccccct aattgagggc cagcttcagt 360ttcatcgttt ttgctgtcgt tgtcatctcc attttcatcg cttttgctgt tgttgtcatc 420ttcattttct ggtgattgct caccaccact ggaaagctct tcctctgcgg ttttatcgga 480ttctaccttc cttgaggcga aaagaggctt cctattagga gcaataaaat ataaagcacc 540agccatagaa agaatcccca ttataaagcc cgctgttttt tcctgattgg agttcctacc 600gaactgaggg gaggacgcca tgagacgtct tgtttggtgt cggcataacc cccttgccac 660ttgaattgac ggcctgtttc tgcacgcatt cctgacgact aagttgcgaa gcattttact 720gataatatac actctttgga tcgagcctac ttccagttgg taattggtgt tccacaattt 780cagcattata tgtttttaaa ccaaaattcg gctccttttc cctttttttc ttattgggtg 840gcgtgccgta cagaacgatt ggcttggtgt gaaatcaaga gcaagcacaa tagatatcaa 900catgaacaat atacaaaagt ctctggcaca gtttgactgc gttagaccag gctagggcat 960ttctgaagct ttacgtatca ctagagaagt tattttggca atg 1003651003DNASaccharomyces cerevisiae 65gaaagatgac ctctttcaaa cgcagtacgc agtttgttga ccatatgcgg ataggtgacg 60tatattttcc agaatggtaa tttggtatct ccggaataac cccagataga ctgtttagat 120acaacttcaa tcgaatcaat agcgtggtca aatgtttcgt ttaaatagtg cacaaacttg 180ttgatttgct cctgatcgtt agcgtcggaa gaattgggcg ctgggacgta aagatagttc 240ttgaaccctg taacattaca aagtacagag tgtccttcac tagtgacacc aaaaaacctt 300accacggtag atgtattttc atctttgata ccattcagta cgctctgttc cgcatcaatt 360tgttggaaag aaatatcata caaacttggg tcaaaatcgg ttggaagttt cttacgctcg 420aatgatgaca ggtcatgctc ttcttggtcg gccatatcat gttccatttg cgatacgtct 480tgttcaaaag tagactctaa ttgcgtaccc attaaatctg tatcctttgc tttgaagcct 540tgactattat attttcgaaa agaatcactc ggaataatct ctattgttga aacaggttca 600cttccaacac catgatctat tgattgccgt ttgattttct tttccaactg gggagtatcc 660tcgtcatcga tcttcacatc aaccatggga agggatcttt tttcactcat tgctgtgcgt 720atatgtataa agattaatgc ttaatagcaa gtgctcaata tctattttcc tttatccttg 780aaaattgcct tagatcagta gtactgagtg tttgttcttc ataagcgaat agcagatgtc 840ctcattgaac attttataga ataaaaagtt acgcgtaata cgaaaaattg cctattacgt 900taaggcatac ttttaccaca caaaaccaag atcaaccgtc aagcaagaac gctgcaaaga 960aacgcagata taaaggagaa caccagatcg aactgcaact atg 1003661003DNASaccharomyces cerevisiae 66tcttgaatgt cgacatatgc ccatcatcag tgaggaatac tcgcgtgaag gatctcatct 60gcgacctgag tgatgatgaa gaagttgcag cactactgaa tttgttgaaa agaaagtata 120aaaatgaaat ccgattgatt gtgaacaatg ctggagtaag ggccaacttc accggattca 180acggcatgga acgggataat cttgataaga tttttaagat aaacacattt gcaccacttc 240agttcattca agaactggcc cctagtagac actcaactag acagtgttat attgtcaata 300tcgcaagcat tttgggcata ttgacgccgg ccaaagtagc agcttatgcg gcgagcaaag 360cagcattgat agcctttcat cagtcgtaca gttttgaatt gcaaaacgaa ggcgtaagaa 420atatcagaac actattagtg accccagggc aactgaatac ggaaatgttt gcaggattca 480agcctcctcg ccagttcttt gcccctgtaa tagacattac tactctagct gccaagatag 540tccgttattg tgagctgggt cagaggggac agctaaatga acccttttat tgtagttttg

600ctcatctttt gatgtgcgta ccttattcgc tacaacgcat tgtaagaagc ttctctcgca 660tagattgctg cctcccggac gagtagaaag ctatacatag taaatagaat atttatagat 720gaatccgagt agacagcctt ggtgtttgct tatacattct ttgcaattat gcacgccctc 780attaccgttg ctcatatttt tgggcattaa ttgtattttg aaaagtgctc gttcaggccc 840gtgtaaaaaa aggtgatgaa gcaaacatta taataaacac ttctgagaag ccacgtgtag 900aggggtaagc tatatcgtaa acaccgttgg atgtggacca cggtgcactg ataaaataaa 960gatatagtag tagaatctgt tactaatctt aacacttttg atg 1003671003DNASaccharomyces cerevisiae 67gctgtagata gatatagaga agccgccaaa acagaactaa gaattctaca gactatcctg 60aataatgacc ctcaaggtca gttccagtgc ctcttgctaa gggagtgctt cgattacaaa 120aatcacattt gtttggtgac agatctatac ggcaggtcca tttacgattt tatgtgctcc 180aacggcattg ccaggttccc cggctctcat attcaggcca ttgccagaca gctaatcaga 240tctgtctgct tcttgcacga tttgggcata atacacacgg atttgaaacc agaaaatatc 300ctgatttgtg acgaaaccca tattgctcaa aaattgcctt tgaaaaccgt acagtcgcta 360agcaagagac gccgtgaagc cagtaagggg aagcgcaaaa tcttgaaaaa tccagaaatc 420aaaatcattg atttcggtag cgcaattttc cattacgaat atcatcctcc tgtaatatcc 480actcgtcact atagagcccc ggaaattgtc cttggcttgg gctggtcgtt cccctgcgac 540atttggtcca tcgcgtgtgt cctagtagaa ctggttattg gcgaatctct ttaccccatt 600catgaaaatc tagaacatat ggctatgatg caacgaatca atggaacccc tttccccaca 660gacattattg ataagatgtt ttacaaatct aaacataaat tgggcaactc tccatcagac 720ctaaattcaa cggtgataaa gcatttcgac agaaaaactt taagcttaca atggcctgaa 780aaaaataaac gcggagatac cataaccacc gaaaagtcaa tgaaaagggt cttgcagtca 840tgtgatcgct tagatattta catctcaaag gtcttgaaac aggattacgg cgatagctta 900agcatcaatt ggaatctacc gccggagaaa aactggtctt tgataaattc gaaattggca 960tggaaaagac aaacacattc ctcttcttcc tcaactactg atg 100368987DNASaccharomyces cerevisiae 68cggtccagaa aagcaactga gattgggagt ataattcggt ggcgttattg gaatacataa 60taggaaaata cggcagatac ctagtcacga aaatatggtg taatctattc gctttttcaa 120tggaaatact aatatcgccc agtacaaact catctacatt tgcatgcggc gaaggcaata 180atggcatagt cgtggtggtg gctactaccg gcgtcttcgt cctatctgca ttgttatttg 240ttgctacgtg gcttgttgct gcaaatggtg gttgatttgt tgtcgttgta acggtggtcg 300acgtagtatg aggggaatat gttttttgaa ttggagagaa ggggccgttc ggagtgttac 360ctgcagagtt gttcttataa aaagccattt gcaaagcagg aggtaaagat tcttttgaat 420tattaggcaa tgctgagtca tttagcagcg ggggcagctt atttggctct gttgcaacca 480agcctttcga atcttgcgct aaagaagatg cgcgcaacgt catgtgagaa gatgcttcat 540tatttgcttt aaatttattc gtattgctgc cctgatttgc ttgtaagagt tggggttccc 600tggacaaata agtttgaact gaaaccttag aatctcgttg agccgcggaa gaagttggag 660aacctgagga aggagaagaa tctgggttag ggataatagt acccggagtt ggagttggat 720gcagattgag cttattcaaa aggctattgc ccatgggaat ctgttgtaaa agatgaacga 780aaacgctgtc attggccaga agagtatcga gtttagattt gatttcatcc acatcttgtc 840tcagtagttg caactgtgag cccttcttag gcctgaattg aggattgatt tcacagtgga 900gaccaatttt ttcgcatctg gagcaaggat gagggaaatt ttgactagca tcgcatttga 960ttttgtgctg tctacaatgt gtacatg 9876930DNAArtificial SequencePrimer 69tttgcgcgcg ggccgcatca tgtaattagt 307030DNAArtificial SequencePrimer 70aaaagatctg accgagcgca gcgagtcagt 307183DNAArtificial SequencePrimer 71cccatgttaa ttaaatctgt tgtttattca attttagccg cttctttggc caatgcaggt 60gcttccaagg tgtacgaccc cga 837232DNAArtificial SequencePrimer 72aaaggcgcgc cttactgctc gttcttcagc ac 327319PRTArtificial SequencePHO5 signal sequence 73Met Leu Ile Lys Ser Val Val Tyr Ser Ile Leu Ala Ala Ser Leu Ala1 5 10 15Asn Ala Gly7431DNAArtificial SequencePrimer 74tttggatcca cggattagaa gccgccgagc g 317535DNAArtificial SequencePrimer 75cccttaatta acatggtttt ttctccttga cgtta 357634DNAArtificial SequencePrimer 76tttggatcct gtgcacgatg gcttcgtttt agcc 347733DNAArtificial SequencePrimer 77cttaattaac atcgagtttc aaaaaattgt aag 337832DNAArtificial SequencePrimer 78cccggatcct ctacgatata tcctgtaaat ag 327934DNAArtificial SequencePrimer 79cttaattaac attttgagta cgtctaatct gtat 348084DNAArtificial SequencePrimer 80cccatgggat ccaaatctgt tgtttattca attttagccg cttctttggc caatgcaggt 60gaagacgcca aaaacataaa gaaa 848134DNAArtificial SequencePrimer 81aaaggcgcgc cttactttcc gcccttcttg gcct 348219PRTArtificial SequencePHO5 signal sequence 82Met Leu Ile Lys Ser Val Val Tyr Ser Ile Leu Ala Ala Ser Leu Ala1 5 10 15Asn Ala Gly8331DNAArtificial SequencePrimer 83tttggatcca cggattagaa gccgccgagc g 318433DNAArtificial SequencePrimer 84tttggatccc atggtttttt ctccttgacg tta 33857393DNAArtificial SequencepSPRT47 85gtacgctgca ggtcgacgga tccccgggtt aattaaatct gttgtttatt caattttagc 60cgcttctttg gccaatgcag gtgcttccaa ggtgtacgac cccgagcaac gcaaacgcat 120gatcactggg cctcagtggt gggctcgctg caagcaaatg aacgtgctgg actccttcat 180caactactat gattccgaga agcacgccga gaacgccgtg atttttctgc atggtaacgc 240tgcctccagc tacctgtgga ggcacgtcgt gcctcacatc gagcccgtgg ctagatgcat 300catccctgat ctgatcggaa tgggtaagtc cggcaagagc gggaatggct catatcgcct 360cctggatcac tacaagtacc tcaccgcttg gttcgagctg ctgaaccttc caaagaaaat 420catctttgtg ggccacgact ggggggcttg tctggccttt cactactcct acgagcacca 480agacaagatc aaggccatcg tccatgctga gagtgtcgtg gacgtgatcg agtcctggga 540cgagtggcct gacatcgagg aggatatcgc cctgatcaag agcgaagagg gcgagaaaat 600ggtgcttgag aataacttct tcgtcgagac catgctccca agcaagatca tgcggaaact 660ggagcctgag gagttcgctg cctacctgga gccattcaag gagaagggcg aggttagacg 720gcctaccctc tcctggcctc gcgagatccc tctcgttaag ggaggcaagc ccgacgtcgt 780ccagattgtc cgcaactaca acgcctacct tcgggccagc gacgatctgc ctaagatgtt 840catcgagtcc gaccctgggt tcttttccaa cgctattgtc gagggagcta agaagttccc 900taacaccgag ttcgtgaagg tgaagggcct ccacttcagc caggaggacg ctccagatga 960aatgggtaag tacatcaaga gcttcgtgga gcgcgtgctg aagaacgagc agtaaggcgc 1020gcgggccgca tcatgtaatt agttatgtca cgcttacatt cacgccctcc ccccacatcc 1080gctctaaccg aaaaggaagg agttagacaa cctgaagtct aggtccctat ttattttttt 1140atagttatgt tagtattaag aacgttattt atatttcaaa tttttctttt ttttctgtac 1200agacgcgtgt acgcatgtaa cattatactg aaaaccttgc ttgagaaggt tttgggacgc 1260tcgaaggctt taatttgcgg ccctgcatta atgaatcggc caacgcgcgg ggagaggcgg 1320tttgcgtatt gggcgctctt ccgcttcctc gctcactgac tcgctgcgct cggtcagatc 1380tgtttagctt gcctcgtccc cgccgggtca cccggccagc gacatggagg cccagaatac 1440cctccttgac agtcttgacg tgcgcagctc aggggcatga tgtgactgtc gcccgtacat 1500ttagcccata catccccatg tataatcatt tgcatccata cattttgatg gccgcacggc 1560gcgaagcaaa aattacggct cctcgctgca gacctgcgag cagggaaacg ctcccctcac 1620agacgcgttg aattgtcccc acgccgcgcc cctgtagaga aatataaaag gttaggattt 1680gccactgagg ttcttctttc atatacttcc ttttaaaatc ttgctaggat acagttctca 1740catcacatcc gaacataaac aaccatgggt aaggaaaaga ctcacgtttc gaggccgcga 1800ttaaattcca acatggatgc tgatttatat gggtataaat gggctcgcga taatgtcggg 1860caatcaggtg cgacaatcta tcgattgtat gggaagcccg atgcgccaga gttgtttctg 1920aaacatggca aaggtagcgt tgccaatgat gttacagatg agatggtcag actaaactgg 1980ctgacggaat ttatgcctct tccgaccatc aagcatttta tccgtactcc tgatgatgca 2040tggttactca ccactgcgat ccccggcaaa acagcattcc aggtattaga agaatatcct 2100gattcaggtg aaaatattgt tgatgcgctg gcagtgttcc tgcgccggtt gcattcgatt 2160cctgtttgta attgtccttt taacagcgat cgcgtatttc gtctcgctca ggcgcaatca 2220cgaatgaata acggtttggt tgatgcgagt gattttgatg acgagcgtaa tggctggcct 2280gttgaacaag tctggaaaga aatgcataag cttttgccat tctcaccgga ttcagtcgtc 2340actcatggtg atttctcact tgataacctt atttttgacg aggggaaatt aataggttgt 2400attgatgttg gacgagtcgg aatcgcagac cgataccagg atcttgccat cctatggaac 2460tgcctcggtg agttttctcc ttcattacag aaacggcttt ttcaaaaata tggtattgat 2520aatcctgata tgaataaatt gcagtttcat ttgatgctcg atgagttttt ctaatcagta 2580ctgacaataa aaagattctt gttttcaaga acttgtcatt tgtatagttt ttttatattg 2640tagttgttct attttaatca aatgttagcg tgatttatat tttttttcgc ctcgacatca 2700tctgcccaga tgcgaagtta agtgcgcaga aagtaatatc atgcgtcaat cgtatgtgaa 2760tgctggtcgc tatactgctg tcgattcgat actaacgccg ccatccagtg tcgaaaacga 2820gctcgaattc ctgggggaac aacttcacag aatgttttgt catattgtcg aagtggtcac 2880aaaacaagag aagttccgcc aattataaaa agggaacccg tatatttcag cttcacggat 2940gatttccagg gtgagagtac tgtatatggg cttacgatag aaggccataa aaatttcttg 3000cttggcaaca aaatagaagt gaaatcatgt cgaggctgct gtgtgggaga acagcttaaa 3060atatcacaaa aaaagaatct aaaacactgt gttgcttgtc ccagaaaggg aatcaagtat 3120ttttataaag attggagtgg taaaaatcga gtatgtgcta gatgctatgg aagatacaaa 3180ttcagcggtc atcactgtat aaattgcaag tatgtaccag aagcacgtga agtgaaaaag 3240gcaaaagaca aaggcgaaaa attgggcatt acgcccgaag gtttgccagt taaaggacca 3300gagtgtataa aatgtggcgg aatcttacag tggcctatgc ggccgctcta gaactagtgg 3360atcgatcccc aattcgccct atagtgagtc gtattacaat tcactggccg tcgttttaca 3420acgtcgtgac tgggaaaacc ctggcgttac ccaacttaat cgccttgcag cacatccccc 3480tttcgccagc tggcgtaata gcgaagaggc ccgcaccgat cgcccttccc aacagttgcg 3540cagcctgaat ggcgaatggc gcctgatgcg gtattttctc cttacgcatc tgtgcggtat 3600ttcacaccgc atacgtcaaa gcaaccatag tacgcgccct gtagcggcgc attaagcgcg 3660gcgggtgtgg tggttacgcg cagcgtgacc gctacacttg ccagcgccct agcgcccgct 3720cctttcgctt tcttcccttc ctttctcgcc acgttcgccg gctttccccg tcaagctcta 3780aatcggggtg ggccatcgcc ctgatagacg gtttttcgcc ctttgacgtt ggagtccacg 3840ttctttaata gtggactctt gttccaaact ggaacaacac tcaaccctat ctcgggctat 3900tcttttgatt tataagggat tttgccgatt tcggcctatt ggttaaaaaa tgagctgatt 3960taacaaaaat ttaacgcgaa ttttaacaaa atattaacgt ttacaatttt atggtgcact 4020ctcagtacaa tctgctctga tgccgcatag ttaagccagc cccgacaccc gccaacaccc 4080gctgacgcgc cctgacgggc ttgtctgctc ccggcatccg cttacagaca agctgtgacc 4140gtctccggga gctgcatgtg tcagaggttt tcaccgtcat caccgaaacg cgcgagacga 4200aagggcctcg tgatacgcct atttttatag gttaatgtca tgataataat ggtttcttag 4260acgtcaggtg gcacttttcg gggaaatgtg cgcggaaccc ctatttgttt atttttctaa 4320atacattcaa atatgtatcc gctcatgaga caataaccct gataaatgct tcaataatat 4380tgaaaaagga agagtatgag tattcaacat ttccgtgtcg cccttattcc cttttttgcg 4440gcattttgcc ttcctgtttt tgctcaccca gaaacgctgg tgaaagtaaa agatgctgaa 4500gatcagttgg gtgcacgagt gggttacatc gaactggatc tcaacagcgg taagatcctt 4560gagagttttc gccccgaaga acgttttcca atgatgagca cttttaaagt tctgctatgt 4620ggcgcggtat tatcccgtat tgacgccggg caagagcaac tcggtcgccg catacactat 4680tctcagaatg acttggttga gtactcacca gtcacagaaa agcatcttac ggatggcatg 4740acagtaagag aattatgcag tgctgccata accatgagtg ataacactgc ggccaactta 4800cttctgacaa cgatcggagg accgaaggag ctaaccgctt ttttgcacaa catgggggat 4860catgtaactc gccttgatcg ttgggaaccg gagctgaatg aagccatacc aaacgacgag 4920cgtgacacca cgatgcctgt agcaatggca acaacgttgc gcaaactatt aactggcgaa 4980ctacttactc tagcttcccg gcaacaatta atagactgga tggaggcgga taaagttgca 5040ggaccacttc tgcgctcggc ccttccggct ggctggttta ttgctgataa atctggagcc 5100ggtgagcgtg ggtctcgcgg tatcattgca gcactggggc cagatggtaa gccctcccgt 5160atcgtagtta tctacacgac ggggagtcag gcaactatgg atgaacgaaa tagacagatc 5220gctgagatag gtgcctcact gattaagcat tggtaactgt cagaccaagt ttactcatat 5280atactttaga ttgatttaaa acttcatttt taatttaaaa ggatctaggt gaagatcctt 5340tttgataatc tcatgaccaa aatcccttaa cgtgagtttt cgttccactg agcgtcagac 5400cccgtagaaa agatcaaagg atcttcttga gatccttttt ttctgcgcgt aatctgctgc 5460ttgcaaacaa aaaaaccacc gctaccagcg gtggtttgtt tgccggatca agagctacca 5520actctttttc cgaaggtaac tggcttcagc agagcgcaga taccaaatac tgtccttcta 5580gtgtagccgt agttaggcca ccacttcaag aactctgtag caccgcctac atacctcgct 5640ctgctaatcc tgttaccagt ggctgctgcc agtggcgata agtcgtgtct taccgggttg 5700gactcaagac gatagttacc ggataaggcg cagcggtcgg gctgaacggg gggttcgtgc 5760acacagccca gcttggagcg aacgacctac accgaactga gatacctaca gcgtgagcat 5820tgagaaagcg ccacgcttcc cgaagggaga aaggcggaca ggtatccggt aagcggcagg 5880gtcggaacag gagagcgcac gagggagctt ccagggggaa acgcctggta tctttatagt 5940cctgtcgggt ttcgccacct ctgacttgag cgtcgatttt tgtgatgctc gtcagggggg 6000cggagcctat ggaaaaacgc cagcaacgcg gcctttttac ggttcctggc cttttgctgg 6060ccttttgctc acatgttctt tcctgcgtta tcccctgatt ctgtggataa ccgtattacc 6120gcctttgagt gagctgatac cgctcgccgc agccgaacga ccgagcgcag cgagtcagtg 6180agcgaggaag cggaagagcg cccaatacgc aaaccgcctc tccccgcgcg ttggccgatt 6240cattaatgca gctggcacga caggtttccc gactggaaag cgggcagtga gcgcaacgca 6300attaatgtga gttagctcac tcattaggca ccccaggctt tacactttat gcttccgcgg 6360ctcgtatgtt gtgtggaatt gtgagcggat aacaatttca cacaggaaac agctatgacc 6420atgattacgc cactagtccg aggcctcgag atccgatatc gccgtggcgg ccgccagctg 6480aagcttaatt atcctgggca cgagtgaaac aaagctaaaa cctttattta gcatggccat 6540tgaatgtaac aattatatat atcgcaagca caaaaaatca aggagagaga actaccactt 6600tgttcatgtg tacaatgttc attatctcca taagcaaaaa aaaaaaatag aaaacatatg 6660ctataaggtt gatattctca cgagtaagcg gcacttgcta cttattgaca ttgcagattt 6720ttggctacag aaatagtata ttagagatta taattgctaa tcaaatcaaa atataaaatt 6780agtaaaccaa accatttata cccttcctta gtagttatgg attgtttttt aatgatattt 6840ctgcaaacca aagaaagatt gttatccaga tagaatttag ttttgatatt catttttttg 6900ttgaagattg aacgccatat ctgggcctca taattcaaaa gacggtgcca ttatcggtag 6960cgtttcgcat tgtactggat ttcagaaatt tcacagttga tgaatcgaaa agaatggtct 7020cattgcaaca cgtaaggtta agatgtccct ttttaccatt ataggcaata aatgaatcat 7080aaaacgaccg tatactggtg aaatagtagg gagaacgagt acctgtagta aaaagtataa 7140atcatagtta atcgggcaat gtccctcgat caaggagtat tgtgtcatgt tcgagacaaa 7200cgccaacatt tttgtttctt ttggacaaat gttgtttgca tttatgatcc gttatatttt 7260gatctaatgt agagttgcac gtagttctta ctggcaaaga aatcgatgca taccaaaaaa 7320gaataaaggt gatatttgat ctttaccgtt tagttccaac gtaaaattgt gcctttggac 7380ttaaaatggc gtc 7393868090DNAArtificial SequencepSPRT50 86gtacgctgca ggtcgacgga tccaaatctg ttgtttattc aattttagcc gcttctttgg 60ccaatgcagg tgaagacgcc aaaaacataa agaaaggccc ggcgccattc tatcctctag 120aggatggaac cgctggagag caactgcata aggctatgaa gagatacgcc ctggttcctg 180gaacaattgc ttttacagat gcacatatcg aggtgaacat cacgtacgcg gaatacttcg 240aaatgtccgt tcggttggca gaagctatga aacgatatgg gctgaataca aatcacagaa 300tcgtcgtatg cagtgaaaac tctcttcaat tctttatgcc ggtgttgggc gcgttattta 360tcggagttgc agttgcgccc gcgaacgaca tttataatga acgtgaattg ctcaacagta 420tgaacatttc gcagcctacc gtagtgtttg tttccaaaaa ggggttgcaa aaaattttga 480acgtgcaaaa aaaattacca ataatccaga aaattattat catggattct aaaacggatt 540accagggatt tcagtcgatg tacacgttcg tcacatctca tctacctccc ggttttaatg 600aatacgattt tgtaccagag tcctttgatc gtgacaaaac aattgcactg ataatgaatt 660cctctggatc tactgggtta cctaagggtg tggcccttcc gcatagaact gcctgcgtca 720gattctcgca tgccagagat cctatttttg gcaatcaaat cattccggat actgcgattt 780taagtgttgt tccattccat cacggttttg gaatgtttac tacactcgga tatttgatat 840gtggatttcg agtcgtctta atgtatagat ttgaagaaga gctgttttta cgatcccttc 900aggattacaa aattcaaagt gcgttgctag taccaaccct attttcattc ttcgccaaaa 960gcactctgat tgacaaatac gatttatcta atttacacga aattgcttct gggggcgcac 1020ctctttcgaa agaagtcggg gaagcggttg caaaacgctt ccatcttcca gggatacgac 1080aaggatatgg gctcactgag actacatcag ctattctgat tacacccgag ggggatgata 1140aaccgggcgc ggtcggtaaa gttgttccat tttttgaagc gaaggttgtg gatctggata 1200ccgggaaaac gctgggcgtt aatcagagag gcgaattatg tgtcagagga cctatgatta 1260tgtccggtta tgtaaacaat ccggaagcga ccaacgcctt gattgacaag gatggatggc 1320tacattctgg agacatagct tactgggacg aagacgaaca cttcttcata gttgaccgct 1380tgaagtcttt aattaaatac aaaggatatc aggtggcccc cgctgaattg gaatcgatat 1440tgttacaaca ccccaacatc ttcgacgcgg gcgtggcagg tcttcccgac gatgacgccg 1500gtgaacttcc cgccgccgtt gttgttttgg agcacggaaa gacgatgacg gaaaaagaga 1560tcgtggatta cgtcgccagt caagtaacaa ccgcgaaaaa gttgcgcgga ggagttgtgt 1620ttgtggacga agtaccgaaa ggtcttaccg gaaaactcga cgcaagaaaa atcagagaga 1680tcctcataaa ggccaagaag ggcggaaagt aaggcgcgcg ggccgcatca tgtaattagt 1740tatgtcacgc ttacattcac gccctccccc cacatccgct ctaaccgaaa aggaaggagt 1800tagacaacct gaagtctagg tccctattta tttttttata gttatgttag tattaagaac 1860gttatttata tttcaaattt ttcttttttt tctgtacaga cgcgtgtacg catgtaacat 1920tatactgaaa accttgcttg agaaggtttt gggacgctcg aaggctttaa tttgcggccc 1980tgcattaatg aatcggccaa cgcgcgggga gaggcggttt gcgtattggg cgctcttccg 2040cttcctcgct cactgactcg ctgcgctcgg tcagatctgt ttagcttgcc tcgtccccgc 2100cgggtcaccc ggccagcgac atggaggccc agaataccct ccttgacagt cttgacgtgc 2160gcagctcagg ggcatgatgt gactgtcgcc cgtacattta gcccatacat ccccatgtat 2220aatcatttgc atccatacat tttgatggcc gcacggcgcg aagcaaaaat tacggctcct 2280cgctgcagac ctgcgagcag ggaaacgctc ccctcacaga cgcgttgaat tgtccccacg 2340ccgcgcccct gtagagaaat ataaaaggtt aggatttgcc actgaggttc ttctttcata 2400tacttccttt taaaatcttg ctaggataca gttctcacat cacatccgaa cataaacaac 2460catgggtaag gaaaagactc acgtttcgag gccgcgatta aattccaaca tggatgctga 2520tttatatggg tataaatggg ctcgcgataa tgtcgggcaa tcaggtgcga caatctatcg 2580attgtatggg aagcccgatg cgccagagtt gtttctgaaa catggcaaag gtagcgttgc 2640caatgatgtt acagatgaga tggtcagact aaactggctg acggaattta tgcctcttcc 2700gaccatcaag cattttatcc gtactcctga tgatgcatgg ttactcacca ctgcgatccc 2760cggcaaaaca gcattccagg tattagaaga atatcctgat tcaggtgaaa atattgttga 2820tgcgctggca gtgttcctgc gccggttgca ttcgattcct gtttgtaatt gtccttttaa 2880cagcgatcgc gtatttcgtc tcgctcaggc gcaatcacga atgaataacg gtttggttga 2940tgcgagtgat tttgatgacg agcgtaatgg ctggcctgtt gaacaagtct ggaaagaaat 3000gcataagctt ttgccattct caccggattc agtcgtcact catggtgatt tctcacttga 3060taaccttatt tttgacgagg ggaaattaat aggttgtatt gatgttggac gagtcggaat 3120cgcagaccga taccaggatc ttgccatcct atggaactgc ctcggtgagt tttctccttc 3180attacagaaa cggctttttc aaaaatatgg tattgataat cctgatatga ataaattgca 3240gtttcatttg atgctcgatg agtttttcta atcagtactg acaataaaaa gattcttgtt 3300ttcaagaact tgtcatttgt atagtttttt tatattgtag ttgttctatt ttaatcaaat

3360gttagcgtga tttatatttt ttttcgcctc gacatcatct gcccagatgc gaagttaagt 3420gcgcagaaag taatatcatg cgtcaatcgt atgtgaatgc tggtcgctat actgctgtcg 3480attcgatact aacgccgcca tccagtgtcg aaaacgagct cgaattcctg ggggaacaac 3540ttcacagaat gttttgtcat attgtcgaag tggtcacaaa acaagagaag ttccgccaat 3600tataaaaagg gaacccgtat atttcagctt cacggatgat ttccagggtg agagtactgt 3660atatgggctt acgatagaag gccataaaaa tttcttgctt ggcaacaaaa tagaagtgaa 3720atcatgtcga ggctgctgtg tgggagaaca gcttaaaata tcacaaaaaa agaatctaaa 3780acactgtgtt gcttgtccca gaaagggaat caagtatttt tataaagatt ggagtggtaa 3840aaatcgagta tgtgctagat gctatggaag atacaaattc agcggtcatc actgtataaa 3900ttgcaagtat gtaccagaag cacgtgaagt gaaaaaggca aaagacaaag gcgaaaaatt 3960gggcattacg cccgaaggtt tgccagttaa aggaccagag tgtataaaat gtggcggaat 4020cttacagtgg cctatgcggc cgctctagaa ctagtggatc gatccccaat tcgccctata 4080gtgagtcgta ttacaattca ctggccgtcg ttttacaacg tcgtgactgg gaaaaccctg 4140gcgttaccca acttaatcgc cttgcagcac atcccccttt cgccagctgg cgtaatagcg 4200aagaggcccg caccgatcgc ccttcccaac agttgcgcag cctgaatggc gaatggcgcc 4260tgatgcggta ttttctcctt acgcatctgt gcggtatttc acaccgcata cgtcaaagca 4320accatagtac gcgccctgta gcggcgcatt aagcgcggcg ggtgtggtgg ttacgcgcag 4380cgtgaccgct acacttgcca gcgccctagc gcccgctcct ttcgctttct tcccttcctt 4440tctcgccacg ttcgccggct ttccccgtca agctctaaat cggggtgggc catcgccctg 4500atagacggtt tttcgccctt tgacgttgga gtccacgttc tttaatagtg gactcttgtt 4560ccaaactgga acaacactca accctatctc gggctattct tttgatttat aagggatttt 4620gccgatttcg gcctattggt taaaaaatga gctgatttaa caaaaattta acgcgaattt 4680taacaaaata ttaacgttta caattttatg gtgcactctc agtacaatct gctctgatgc 4740cgcatagtta agccagcccc gacacccgcc aacacccgct gacgcgccct gacgggcttg 4800tctgctcccg gcatccgctt acagacaagc tgtgaccgtc tccgggagct gcatgtgtca 4860gaggttttca ccgtcatcac cgaaacgcgc gagacgaaag ggcctcgtga tacgcctatt 4920tttataggtt aatgtcatga taataatggt ttcttagacg tcaggtggca cttttcgggg 4980aaatgtgcgc ggaaccccta tttgtttatt tttctaaata cattcaaata tgtatccgct 5040catgagacaa taaccctgat aaatgcttca ataatattga aaaaggaaga gtatgagtat 5100tcaacatttc cgtgtcgccc ttattccctt ttttgcggca ttttgccttc ctgtttttgc 5160tcacccagaa acgctggtga aagtaaaaga tgctgaagat cagttgggtg cacgagtggg 5220ttacatcgaa ctggatctca acagcggtaa gatccttgag agttttcgcc ccgaagaacg 5280ttttccaatg atgagcactt ttaaagttct gctatgtggc gcggtattat cccgtattga 5340cgccgggcaa gagcaactcg gtcgccgcat acactattct cagaatgact tggttgagta 5400ctcaccagtc acagaaaagc atcttacgga tggcatgaca gtaagagaat tatgcagtgc 5460tgccataacc atgagtgata acactgcggc caacttactt ctgacaacga tcggaggacc 5520gaaggagcta accgcttttt tgcacaacat gggggatcat gtaactcgcc ttgatcgttg 5580ggaaccggag ctgaatgaag ccataccaaa cgacgagcgt gacaccacga tgcctgtagc 5640aatggcaaca acgttgcgca aactattaac tggcgaacta cttactctag cttcccggca 5700acaattaata gactggatgg aggcggataa agttgcagga ccacttctgc gctcggccct 5760tccggctggc tggtttattg ctgataaatc tggagccggt gagcgtgggt ctcgcggtat 5820cattgcagca ctggggccag atggtaagcc ctcccgtatc gtagttatct acacgacggg 5880gagtcaggca actatggatg aacgaaatag acagatcgct gagataggtg cctcactgat 5940taagcattgg taactgtcag accaagttta ctcatatata ctttagattg atttaaaact 6000tcatttttaa tttaaaagga tctaggtgaa gatccttttt gataatctca tgaccaaaat 6060cccttaacgt gagttttcgt tccactgagc gtcagacccc gtagaaaaga tcaaaggatc 6120ttcttgagat cctttttttc tgcgcgtaat ctgctgcttg caaacaaaaa aaccaccgct 6180accagcggtg gtttgtttgc cggatcaaga gctaccaact ctttttccga aggtaactgg 6240cttcagcaga gcgcagatac caaatactgt ccttctagtg tagccgtagt taggccacca 6300cttcaagaac tctgtagcac cgcctacata cctcgctctg ctaatcctgt taccagtggc 6360tgctgccagt ggcgataagt cgtgtcttac cgggttggac tcaagacgat agttaccgga 6420taaggcgcag cggtcgggct gaacgggggg ttcgtgcaca cagcccagct tggagcgaac 6480gacctacacc gaactgagat acctacagcg tgagcattga gaaagcgcca cgcttcccga 6540agggagaaag gcggacaggt atccggtaag cggcagggtc ggaacaggag agcgcacgag 6600ggagcttcca gggggaaacg cctggtatct ttatagtcct gtcgggtttc gccacctctg 6660acttgagcgt cgatttttgt gatgctcgtc aggggggcgg agcctatgga aaaacgccag 6720caacgcggcc tttttacggt tcctggcctt ttgctggcct tttgctcaca tgttctttcc 6780tgcgttatcc cctgattctg tggataaccg tattaccgcc tttgagtgag ctgataccgc 6840tcgccgcagc cgaacgaccg agcgcagcga gtcagtgagc gaggaagcgg aagagcgccc 6900aatacgcaaa ccgcctctcc ccgcgcgttg gccgattcat taatgcagct ggcacgacag 6960gtttcccgac tggaaagcgg gcagtgagcg caacgcaatt aatgtgagtt agctcactca 7020ttaggcaccc caggctttac actttatgct tccgcggctc gtatgttgtg tggaattgtg 7080agcggataac aatttcacac aggaaacagc tatgaccatg attacgccac tagtccgagg 7140cctcgagatc cgatatcgcc gtggcggccg ccagctgaag cttaattatc ctgggcacga 7200gtgaaacaaa gctaaaacct ttatttagca tggccattga atgtaacaat tatatatatc 7260gcaagcacaa aaaatcaagg agagagaact accactttgt tcatgtgtac aatgttcatt 7320atctccataa gcaaaaaaaa aaaatagaaa acatatgcta taaggttgat attctcacga 7380gtaagcggca cttgctactt attgacattg cagatttttg gctacagaaa tagtatatta 7440gagattataa ttgctaatca aatcaaaata taaaattagt aaaccaaacc atttataccc 7500ttccttagta gttatggatt gttttttaat gatatttctg caaaccaaag aaagattgtt 7560atccagatag aatttagttt tgatattcat ttttttgttg aagattgaac gccatatctg 7620ggcctcataa ttcaaaagac ggtgccatta tcggtagcgt ttcgcattgt actggatttc 7680agaaatttca cagttgatga atcgaaaaga atggtctcat tgcaacacgt aaggttaaga 7740tgtccctttt taccattata ggcaataaat gaatcataaa acgaccgtat actggtgaaa 7800tagtagggag aacgagtacc tgtagtaaaa agtataaatc atagttaatc gggcaatgtc 7860cctcgatcaa ggagtattgt gtcatgttcg agacaaacgc caacattttt gtttcttttg 7920gacaaatgtt gtttgcattt atgatccgtt atattttgat ctaatgtaga gttgcacgta 7980gttcttactg gcaaagaaat cgatgcatac caaaaaagaa taaaggtgat atttgatctt 8040taccgtttag ttccaacgta aaattgtgcc tttggactta aaatggcgtc 8090877103DNAArtificial SequencepSPRT190 87tcgaggcggc cgccaaaata gaatttgaag gagatgattt gttttcctcc caagtgcctc 60cactgacgtt taaaatgttc ctgatcatca gatgaccttc ctcggtcaag atggattccg 120gatgaaattg cacaccttct acagtgtact tcttgtgtct tacacccatg ataattccat 180tttcggtact cgcagtaacc ttcaagcagg atggtaggga cgattctgtc ccggccaatg 240aatggtatct tgtcacagca ataccttgcg gcacgttctt gaaaattcca cagttgtcgt 300gagagattgg ggacgtttta ccgtggacaa tctcaccagc gtaggcaact tcaccaccaa 360atacgtcaaa catgcattgc tggcccatac agattccaaa tacaggaatt ttcccagtaa 420agtaccggat acagtctctt gaaatgccag aatctgtctt tgggtggcct ggtccaggcg 480agataagcaa tgtgtcggga ttcaaggcgg caatttctgg aactgtaatt gcatcgttac 540ggtagacgct cactttggcg ccctcctggc acaagtactc gtaaacgttc caggtaaagg 600aatcgtagtt gtcaattaga accacatgct tattgattgg gtttgttgca gcgtgcacag 660acatatttaa atcgaggcgc gccatgttaa ttaaatctgt tgtttattca attttagccg 720cttctttggc caatgcaggt gcttccaagg tgtacgaccc cgagcaacgc aaacgcatga 780tcactgggcc tcagtggtgg gctcgctgca agcaaatgaa cgtgctggac tccttcatca 840actactatga ttccgagaag cacgccgaga acgccgtgat ttttctgcat ggtaacgctg 900cctccagcta cctgtggagg cacgtcgtgc ctcacatcga gcccgtggct agatgcatca 960tccctgatct gatcggaatg ggtaagtccg gcaagagcgg gaatggctca tatcgcctcc 1020tggatcacta caagtacctc accgcttggt tcgagctgct gaaccttcca aagaaaatca 1080tctttgtggg ccacgactgg ggggcttgtc tggcctttca ctactcctac gagcaccaag 1140acaagatcaa ggccatcgtc catgctgaga gtgtcgtgga cgtgatcgag tcctgggacg 1200agtggcctga catcgaggag gatatcgccc tgatcaagag cgaagagggc gagaaaatgg 1260tgcttgagaa taacttcttc gtcgagacca tgctcccaag caagatcatg cggaaactgg 1320agcctgagga gttcgctgcc tacctggagc cattcaagga gaagggcgag gttagacggc 1380ctaccctctc ctggcctcgc gagatccctc tcgttaaggg aggcaagccc gacgtcgtcc 1440agattgtccg caactacaac gcctaccttc gggccagcga cgatctgcct aagatgttca 1500tcgagtccga ccctgggttc ttttccaacg ctattgtcga gggagctaag aagttcccta 1560acaccgagtt cgtgaaggtg aagggcctcc acttcagcca ggaggacgct ccagatgaaa 1620tgggtaagta catcaagagc ttcgtggagc gcgtgctgaa gaacgagcag taaggcgcgc 1680gggccgcatc atgtaattag ttatgtcacg cttacattca cgccctcccc ccacatccgc 1740tctaaccgaa aaggaaggag ttagacaacc tgaagtctag gtccctattt atttttttat 1800agttatgtta gtattaagaa cgttatttat atttcaaatt tttctttttt ttctgtacag 1860acgcgtgtac gcatgtaaca ttatactgaa aaccttgctt gagaaggttt tgggacgctc 1920gaaggcttta atttgcggcc ctgcattaat gaatcggcca acgcgcgggg agaggcggtt 1980tgcgtattgg gcgctcttcc gcttcctcgc tcactgactc gctgcgctcg gtcagatctg 2040tttagcttgc ctcgtccccg ccgggtcacc cggccagcga catggaggcc cagaataccc 2100tccttgacag tcttgacgtg cgcagctcag gggcatgatg tgactgtcgc ccgtacattt 2160agcccataca tccccatgta taatcatttg catccataca ttttgatggc cgcacggcgc 2220gaagcaaaaa ttacggctcc tcgctgcaga cctgcgagca gggaaacgct cccctcacag 2280acgcgttgaa ttgtccccac gccgcgcccc tgtagagaaa tataaaaggt taggatttgc 2340cactgaggtt cttctttcat atacttcctt ttaaaatctt gctaggatac agttctcaca 2400tcacatccga acataaacaa ccatgggtaa ggaaaagact cacgtttcga ggccgcgatt 2460aaattccaac atggatgctg atttatatgg gtataaatgg gctcgcgata atgtcgggca 2520atcaggtgcg acaatctatc gattgtatgg gaagcccgat gcgccagagt tgtttctgaa 2580acatggcaaa ggtagcgttg ccaatgatgt tacagatgag atggtcagac taaactggct 2640gacggaattt atgcctcttc cgaccatcaa gcattttatc cgtactcctg atgatgcatg 2700gttactcacc actgcgatcc ccggcaaaac agcattccag gtattagaag aatatcctga 2760ttcaggtgaa aatattgttg atgcgctggc agtgttcctg cgccggttgc attcgattcc 2820tgtttgtaat tgtcctttta acagcgatcg cgtatttcgt ctcgctcagg cgcaatcacg 2880aatgaataac ggtttggttg atgcgagtga ttttgatgac gagcgtaatg gctggcctgt 2940tgaacaagtc tggaaagaaa tgcataagct tttgccattc tcaccggatt cagtcgtcac 3000tcatggtgat ttctcacttg ataaccttat ttttgacgag gggaaattaa taggttgtat 3060tgatgttgga cgagtcggaa tcgcagaccg ataccaggat cttgccatcc tatggaactg 3120cctcggtgag ttttctcctt cattacagaa acggcttttt caaaaatatg gtattgataa 3180tcctgatatg aataaattgc agtttcattt gatgctcgat gagtttttct aatcagtact 3240gacaataaaa agattcttgt tttcaagaac ttgtcatttg tatagttttt ttatattgta 3300gttgttctat tttaatcaaa tgttagcgtg atttatattt tttttcgcct cgacatcatc 3360tgcccagatg cgaagttaag tgcgcagaaa gtaatatcat gcgtcaatcg tatgtgaatg 3420ctggtcgcta tactgctgtc gattcgatac taacgccgcc atccagtgtc gaaaacgagc 3480tcgaattcct gggggaacaa cttcacagaa tgttttgtca tattgtcgaa gtggtcacaa 3540aacaagagaa gttccgccaa ttataaaaag ggaacccgta tatttcagct tcacggatga 3600tttccagggt gagagtactg tatatgggct tacgatagaa ggccataaaa atttcttgct 3660tggcaacaaa atagaagtga aatcatgtcg aggctgctgt gtgggagaac agcttaaaat 3720atcacaaaaa aagaatctaa aacactgtgt tgcttgtccc agaaagggaa tcaagtattt 3780ttataaagat tggagtggta aaaatcgagt atgtgctaga tgctatggaa gatacaaatt 3840cagcggtcat cactgtataa attgcaagta tgtaccagaa gcacgtgaag tgaaaaaggc 3900aaaagacaaa ggcgaaaaat tgggcattac gcccgaaggt ttgccagtta aaggaccaga 3960gtgtataaaa tgtggcggaa tcttacagtg gcctatgcgg ccgctctaga actagtggat 4020cgatccccaa ttcgccctat agtgagtcgt attacaattc actggccgtc gttttacaac 4080gtcgtgactg ggaaaaccct ggcgttaccc aacttaatcg ccttgcagca catccccctt 4140tcgccagctg gcgtaatagc gaagaggccc gcaccgatcg cccttcccaa cagttgcgca 4200gcctgaatgg cgaatggcgc ctgatgcggt attttctcct tacgcatctg tgcggtattt 4260cacaccgcat acgtcaaagc aaccatagta cgcgccctgt agcggcgcat taagcgcggc 4320gggtgtggtg gttacgcgca gcgtgaccgc tacacttgcc agcgccctag cgcccgctcc 4380tttcgctttc ttcccttcct ttctcgccac gttcgccggc tttccccgtc aagctctaaa 4440tcggggtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 4500ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cgggctattc 4560ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 4620acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaattttat ggtgcactct 4680cagtacaatc tgctctgatg ccgcatagtt aagccagccc cgacacccgc caacacccgc 4740tgacgcgccc tgacgggctt gtctgctccc ggcatccgct tacagacaag ctgtgaccgt 4800ctccgggagc tgcatgtgtc agaggttttc accgtcatca ccgaaacgcg cgagacgaaa 4860gggcctcgtg atacgcctat ttttataggt taatgtcatg ataataatgg tttcttagac 4920gtcaggtggc acttttcggg gaaatgtgcg cggaacccct atttgtttat ttttctaaat 4980acattcaaat atgtatccgc tcatgagaca ataaccctga taaatgcttc aataatattg 5040aaaaaggaag agtatgagta ttcaacattt ccgtgtcgcc cttattccct tttttgcggc 5100attttgcctt cctgtttttg ctcacccaga aacgctggtg aaagtaaaag atgctgaaga 5160tcagttgggt gcacgagtgg gttacatcga actggatctc aacagcggta agatccttga 5220gagttttcgc cccgaagaac gttttccaat gatgagcact tttaaagttc tgctatgtgg 5280cgcggtatta tcccgtattg acgccgggca agagcaactc ggtcgccgca tacactattc 5340tcagaatgac ttggttgagt actcaccagt cacagaaaag catcttacgg atggcatgac 5400agtaagagaa ttatgcagtg ctgccataac catgagtgat aacactgcgg ccaacttact 5460tctgacaacg atcggaggac cgaaggagct aaccgctttt ttgcacaaca tgggggatca 5520tgtaactcgc cttgatcgtt gggaaccgga gctgaatgaa gccataccaa acgacgagcg 5580tgacaccacg atgcctgtag caatggcaac aacgttgcgc aaactattaa ctggcgaact 5640acttactcta gcttcccggc aacaattaat agactggatg gaggcggata aagttgcagg 5700accacttctg cgctcggccc ttccggctgg ctggtttatt gctgataaat ctggagccgg 5760tgagcgtggg tctcgcggta tcattgcagc actggggcca gatggtaagc cctcccgtat 5820cgtagttatc tacacgacgg ggagtcaggc aactatggat gaacgaaata gacagatcgc 5880tgagataggt gcctcactga ttaagcattg gtaactgtca gaccaagttt actcatatat 5940actttagatt gatttaaaac ttcattttta atttaaaagg atctaggtga agatcctttt 6000tgataatctc atgaccaaaa tcccttaacg tgagttttcg ttccactgag cgtcagaccc 6060cgtagaaaag atcaaaggat cttcttgaga tccttttttt ctgcgcgtaa tctgctgctt 6120gcaaacaaaa aaaccaccgc taccagcggt ggtttgtttg ccggatcaag agctaccaac 6180tctttttccg aaggtaactg gcttcagcag agcgcagata ccaaatactg tccttctagt 6240gtagccgtag ttaggccacc acttcaagaa ctctgtagca ccgcctacat acctcgctct 6300gctaatcctg ttaccagtgg ctgctgccag tggcgataag tcgtgtctta ccgggttgga 6360ctcaagacga tagttaccgg ataaggcgca gcggtcgggc tgaacggggg gttcgtgcac 6420acagcccagc ttggagcgaa cgacctacac cgaactgaga tacctacagc gtgagcattg 6480agaaagcgcc acgcttcccg aagggagaaa ggcggacagg tatccggtaa gcggcagggt 6540cggaacagga gagcgcacga gggagcttcc agggggaaac gcctggtatc tttatagtcc 6600tgtcgggttt cgccacctct gacttgagcg tcgatttttg tgatgctcgt caggggggcg 6660gagcctatgg aaaaacgcca gcaacgcggc ctttttacgg ttcctggcct tttgctggcc 6720ttttgctcac atgttctttc ctgcgttatc ccctgattct gtggataacc gtattaccgc 6780ctttgagtga gctgataccg ctcgccgcag ccgaacgacc gagcgcagcg agtcagtgag 6840cgaggaagcg gaagagcgcc caatacgcaa accgcctctc cccgcgcgtt ggccgattca 6900ttaatgcagc tggcacgaca ggtttcccga ctggaaagcg ggcagtgagc gcaacgcaat 6960taatgtgagt tagctcactc attaggcacc ccaggcttta cactttatgc ttccgcggct 7020cgtatgttgt gtggaattgt gagcggataa caatttcaca caggaaacag ctatgaccat 7080gattacgcca ctagtccgag gcc 7103889685DNAArtificial SequencepSPRT192 88taaatctgtt gtttattcaa ttttagccgc ttctttggcc aatgcaggtg cttccaaggt 60gtacgacccc gagcaacgca aacgcatgat cactgggcct cagtggtggg ctcgctgcaa 120gcaaatgaac gtgctggact ccttcatcaa ctactatgat tccgagaagc acgccgagaa 180cgccgtgatt tttctgcatg gtaacgctgc ctccagctac ctgtggaggc acgtcgtgcc 240tcacatcgag cccgtggcta gatgcatcat ccctgatctg atcggaatgg gtaagtccgg 300caagagcggg aatggctcat atcgcctcct ggatcactac aagtacctca ccgcttggtt 360cgagctgctg aaccttccaa agaaaatcat ctttgtgggc cacgactggg gggcttgtct 420ggcctttcac tactcctacg agcaccaaga caagatcaag gccatcgtcc atgctgagag 480tgtcgtggac gtgatcgagt cctgggacga gtggcctgac atcgaggagg atatcgccct 540gatcaagagc gaagagggcg agaaaatggt gcttgagaat aacttcttcg tcgagaccat 600gctcccaagc aagatcatgc ggaaactgga gcctgaggag ttcgctgcct acctggagcc 660attcaaggag aagggcgagg ttagacggcc taccctctcc tggcctcgcg agatccctct 720cgttaaggga ggcaagcccg acgtcgtcca gattgtccgc aactacaacg cctaccttcg 780ggccagcgac gatctgccta agatgttcat cgagtccgac cctgggttct tttccaacgc 840tattgtcgag ggagctaaga agttccctaa caccgagttc gtgaaggtga agggcctcca 900cttcagccag gaggacgctc cagatgaaat gggtaagtac atcaagagct tcgtggagcg 960cgtgctgaag aacgagcagt aaggcgcgcg ggccgcatca tgtaattagt tatgtcacgc 1020ttacattcac gccctccccc cacatccgct ctaaccgaaa aggaaggagt tagacaacct 1080gaagtctagg tccctattta tttttttata gttatgttag tattaagaac gttatttata 1140tttcaaattt ttcttttttt tctgtacaga cgcgtgtacg catgtaacat tatactgaaa 1200accttgcttg agaaggtttt gggacgctcg aaggctttaa tttgcggccc tgcattaatg 1260aatcggccaa cgcgcgggga gaggcggttt gcgtattggg cgctcttccg cttcctcgct 1320cactgactcg ctgcgctcgg tcagatctcg ctgttccagt caatcagggt attgaagctc 1380atggtcttta ctccatcaca gggttccgcc ttatccggcc tacagaaccc aaaatatcaa 1440cgcattacgt aggcctgata agcgcagcgc catcaggcgt cagatcactc catcatcttc 1500tcgatcggca gtaccagaat cgagctggcg ccaagcgctt tcagtttctc catggtttcc 1560cagaacaacg tttcgctgct gaccatgtgc atcgccacgc gctgttgctc gcctgccagc 1620ggcagaattg tcggcctttc ggcgcctggc agcagggcga taacctcttc caggcgttca 1680cttggcgcgt gcatcatgat gtatttcgat tcgcgcgcct gaatcacgcc ctgaatacgg 1740gtcagcaatt tatcgatcag ctcttgcttg ctctgtgcca tctcaccgtc gcgctgaatc 1800agacaggctt tagagcggta gataacttcg acttcacgca ggccgttagc ttcaagcgtc 1860gcgccggtag agaccaaatc gcagatagcg tcggccagcc ccgcgcgcgg cgcgacttcg 1920acagaaccat ttaacagaca cgatttaaaa gagacgcctt tctggtcgag gtagcgtttg 1980aggaggtgcg gatatgaggt agcgatacgt ttaccgtcca gcgcggccgg gccgtcccag 2040gcttcgtcaa ccggtgttgc cagcgataaa cggcagccgc cgaagtcaag acggcgcagg 2100gttaaatagc gtggatcttc gccctgtgcg cggcggttga gtagctcttc ttccagcacg 2160ttttcgccga taataccgag atcgaccacg ccatccatta ccagacccgg aatgtcatca 2220tcacgcacgc gcaggatatc aatcggcatg ttttccgcca tcgcaatcag gcgctgagtg 2280tgtaaattaa tttttatgcc gcagcgggcc agcaattctc gtgaatcatc gcttaaacgg 2340cctgatttct gaatagctat gcgtaagcgg gtgttgtcta acattctgcg ttcctcttta 2400tcctgtctga accggtctgt atcgcgcgcc aaaaaaaaag cccccggaag atgatcttcc 2460gggggctttc tcatgcgttc atgcaccact ggaagatcca caggacgggt gtggtcgcca 2520tgatcgcgta gtcgatagtg gctccaagta gcgaagcgag caggactggg cggcggccaa 2580agcggtcgga cagtgctccg agaacgggtg cgcatagaaa ttgcatcaac gcatatagcg 2640ctagcagcac gccatagtga ctggcgatgc tgtcggaatg gacgatatcc cgcaagaggc 2700ccggcagtac cggcataacc aagcctatgc ctacagcatc cagggtgacg gtgccgagga 2760tgacgatgag cgcattgtta gatttcatac acggtgcctg actgcgttag caatttaact 2820gtgataaact accgcattaa agctttttct ttccaatttt ttttttttcg tcattataaa 2880aatcattacg accgagattc ccgggtaata actgatataa ttaaattgaa gctctaattt 2940gtgagtttag tatacatgca tttacttata atacagtttt ttagttttgc tggccgcatc 3000ttctcaaata tgcttcccag cctgcttttc tgtaacgttc accctctacc ttagcatccc 3060ttccctttgc aaatagtcct cttccaacaa taataatgtc agatcctgta

gagaccacat 3120catccacggt tctatactgt tgacccaatg cgtctccctt gtcatctaaa cccacaccgg 3180gtgtcataat caaccaatcg taaccttcat ctcttccacc catgtctctt tgagcaataa 3240agccgataac aaaatctttg tcgctcttcg caatgtcaac agtaccctta gtatattctc 3300cagtagatag ggagcccttg catgacaatt ctgctaacat caaaaggcct ctaggttcct 3360ttgttacttc ttctgccgcc tgcttcaaac cgctaacaat acctgggccc accacaccgt 3420gtgcattcgt aatgtctgcc cattctgcta ttctgtatac acccgcagag tactgcaatt 3480tgactgtatt accaatgtca gcaaattttc tgtcttcgaa gagtaaaaaa ttgtacttgg 3540cggataatgc ctttagcggc ttaactgtgc cctccatgga aaaatcagtc aagatatcca 3600catgtgtttt tagtaaacaa attttgggac ctaatgcttc aactaactcc agtaattcct 3660tggtggtacg aacatccaat gaagcacaca agtttgtttg cttttcgtgc atgatattaa 3720atagcttggc agcaacagga ctaggatgag tagcagcacg ttccttatat gtagctttcg 3780acatgattta tcttcgtttc ctgcaggttt ttgttctgtg cagttgggtt aagaatactg 3840ggcaatttca tgtttcttca acactacata tgcgtatata taccaatcta agtctgtgct 3900ccttccttcg ttcttccttc tgttcggaga ttaccgaatc aaaaaaattt caaagaaacc 3960gaaatcaaaa aaaagaataa aaaaaaaatg atgaattgaa ttgaaaagct tatcgatgat 4020aagctgtcaa acatgagaat taattcagat ccgctgttcc agtcaatcag ggtattgaag 4080ctcatggtct ttactccatc acagggttcc gccttatccg gcctacagaa cccaaaatat 4140caacgcatta cgtaggcctg ataagcgcag cgccatcagg cgtcagatca ctccatcatc 4200ttctcgatcg gcagtaccag aatcgagctg gcgccaagcg ctttcagttt ctccatggtt 4260tcccagaaca acgtttcgct gctgaccatg tgcatcgcca cgcgctgttg ctcgcctgcc 4320agcggcagaa ttgtcggcct ttcggcgcct ggcagcaggg cgataacctc ttccaggcgt 4380tcacttggcg cgtgcatcat gatgtatttc gattcgcgcg cctgaatcac gccctgaata 4440cgggtcagca atttatcgat cagctcttgc ttgctctgtg ccatctcacc gtcgcgctga 4500atcagacagg ctttagagcg gtagataact tcgacttcac gcaggccgtt agcttcaagc 4560gtcgcgccgg tagagaccaa atcgcagata gcgtcggcca gccccgcgcg cggcgcgact 4620tcgacagaac catttaacag acacgattta aaagagacgc ctttctggtc gaggtagcgt 4680ttgaggaggt gcggatatga ggtagcgata cgtttaccgt ccagcgcggc cgggccgtcc 4740caggcttcgt caaccggtgt tgccagcgat aaacggcagc cgccgaagtc aagacggcgc 4800agggttaaat agcgtggatc ttcgccctgt gcgcggcggt tgagtagctc ttcttccagc 4860acgttttcgc cgataatacc gagatcgacc acgccatcca ttaccagacc cggaatgtca 4920tcatcacgca cgcgcaggat atcaatcggc atgttttccg ccatcgcaat caggcgctga 4980gtgtgtaaat taatttttat gccgcagcgg gccagcaatt ctcgtgaatc atcgcttaaa 5040cggcctgatt tctgaatagc tatgcgtaag cgggtgttgt ctaacattct gcgttcctct 5100ttatcctgtc tgaaccggtc tgtatcgcgc gccaaaaaaa aagcccccgg aagatgatct 5160tccgggggct ttctcatgcg ttcatgcacc actggaagat cagatctgtt tagcttgcct 5220cgtccccgcc gggtcacccg gccagcgaca tggggtattt aggtctacgt tgaatgaatg 5280caggtcccta ttattgacac ctacaacttt agcaccaatt tctagagccc tttgtaattc 5340ctctttggag ttcacctcaa cgagaggttc catgttcaaa tctttactgt agctgtacag 5400ttccttcaat aagggttgag atagcatctt gactataaga aggacagtgt cagctccagc 5460taatcttgct tctagtattt gatacttgct gaaaataaat tcttttctca aaacacaagg 5520cctctccttg ggaggaaatt tcaaatctag gattttcctc acatttacta aatcctgtaa 5580cgaaccgtga aaccaatgag gttcggtcaa tacggaaatt gcggatgcac cagcctctgc 5640gtatttgaga gcctgttcag cagcaacagc ttttaaacaa atgggtccct tcgatggaga 5700ggcacgcttg acttcagcaa gaacaacggc tcttttatgg gatgatgaca acaccgtgta 5760gaaatcctgt aacggtgggg caagacctaa atcatagtta gattgtaagt cttgaaaggt 5820gaaacctggg attttagact gctcattgac gtctatttta cgccgagcat agatacggtc 5880ggcctatgcg gccgctctag aactagtgga tcgatcccca attcgcccta tagtgagtcg 5940tattacaatt cactggccgt cgttttacaa cgtcgtgact gggaaaaccc tggcgttacc 6000caacttaatc gccttgcagc acatccccct ttcgccagct ggcgtaatag cgaagaggcc 6060cgcaccgatc gcccttccca acagttgcgc agcctgaatg gcgaatggcg cctgatgcgg 6120tattttctcc ttacgcatct gtgcggtatt tcacaccgca tacgtcaaag caaccatagt 6180acgcgccctg tagcggcgca ttaagcgcgg cgggtgtggt ggttacgcgc agcgtgaccg 6240ctacacttgc cagcgcccta gcgcccgctc ctttcgcttt cttcccttcc tttctcgcca 6300cgttcgccgg ctttccccgt caagctctaa atcggggtgg gccatcgccc tgatagacgg 6360tttttcgccc tttgacgttg gagtccacgt tctttaatag tggactcttg ttccaaactg 6420gaacaacact caaccctatc tcgggctatt cttttgattt ataagggatt ttgccgattt 6480cggcctattg gttaaaaaat gagctgattt aacaaaaatt taacgcgaat tttaacaaaa 6540tattaacgtt tacaatttta tggtgcactc tcagtacaat ctgctctgat gccgcatagt 6600taagccagcc ccgacacccg ccaacacccg ctgacgcgcc ctgacgggct tgtctgctcc 6660cggcatccgc ttacagacaa gctgtgaccg tctccgggag ctgcatgtgt cagaggtttt 6720caccgtcatc accgaaacgc gcgagacgaa agggcctcgt gatacgccta tttttatagg 6780ttaatgtcat gataataatg gtttcttaga cgtcaggtgg cacttttcgg ggaaatgtgc 6840gcggaacccc tatttgttta tttttctaaa tacattcaaa tatgtatccg ctcatgagac 6900aataaccctg ataaatgctt caataatatt gaaaaaggaa gagtatgagt attcaacatt 6960tccgtgtcgc ccttattccc ttttttgcgg cattttgcct tcctgttttt gctcacccag 7020aaacgctggt gaaagtaaaa gatgctgaag atcagttggg tgcacgagtg ggttacatcg 7080aactggatct caacagcggt aagatccttg agagttttcg ccccgaagaa cgttttccaa 7140tgatgagcac ttttaaagtt ctgctatgtg gcgcggtatt atcccgtatt gacgccgggc 7200aagagcaact cggtcgccgc atacactatt ctcagaatga cttggttgag tactcaccag 7260tcacagaaaa gcatcttacg gatggcatga cagtaagaga attatgcagt gctgccataa 7320ccatgagtga taacactgcg gccaacttac ttctgacaac gatcggagga ccgaaggagc 7380taaccgcttt tttgcacaac atgggggatc atgtaactcg ccttgatcgt tgggaaccgg 7440agctgaatga agccatacca aacgacgagc gtgacaccac gatgcctgta gcaatggcaa 7500caacgttgcg caaactatta actggcgaac tacttactct agcttcccgg caacaattaa 7560tagactggat ggaggcggat aaagttgcag gaccacttct gcgctcggcc cttccggctg 7620gctggtttat tgctgataaa tctggagccg gtgagcgtgg gtctcgcggt atcattgcag 7680cactggggcc agatggtaag ccctcccgta tcgtagttat ctacacgacg gggagtcagg 7740caactatgga tgaacgaaat agacagatcg ctgagatagg tgcctcactg attaagcatt 7800ggtaactgtc agaccaagtt tactcatata tactttagat tgatttaaaa cttcattttt 7860aatttaaaag gatctaggtg aagatccttt ttgataatct catgaccaaa atcccttaac 7920gtgagttttc gttccactga gcgtcagacc ccgtagaaaa gatcaaagga tcttcttgag 7980atcctttttt tctgcgcgta atctgctgct tgcaaacaaa aaaaccaccg ctaccagcgg 8040tggtttgttt gccggatcaa gagctaccaa ctctttttcc gaaggtaact ggcttcagca 8100gagcgcagat accaaatact gtccttctag tgtagccgta gttaggccac cacttcaaga 8160actctgtagc accgcctaca tacctcgctc tgctaatcct gttaccagtg gctgctgcca 8220gtggcgataa gtcgtgtctt accgggttgg actcaagacg atagttaccg gataaggcgc 8280agcggtcggg ctgaacgggg ggttcgtgca cacagcccag cttggagcga acgacctaca 8340ccgaactgag atacctacag cgtgagcatt gagaaagcgc cacgcttccc gaagggagaa 8400aggcggacag gtatccggta agcggcaggg tcggaacagg agagcgcacg agggagcttc 8460cagggggaaa cgcctggtat ctttatagtc ctgtcgggtt tcgccacctc tgacttgagc 8520gtcgattttt gtgatgctcg tcaggggggc ggagcctatg gaaaaacgcc agcaacgcgg 8580cctttttacg gttcctggcc ttttgctggc cttttgctca catgttcttt cctgcgttat 8640cccctgattc tgtggataac cgtattaccg cctttgagtg agctgatacc gctcgccgca 8700gccgaacgac cgagcgcagc gagtcagtga gcgaggaagc ggaagagcgc ccaatacgca 8760aaccgcctct ccccgcgcgt tggccgattc attaatgcag ctggcacgac aggtttcccg 8820actggaaagc gggcagtgag cgcaacgcaa ttaatgtgag ttagctcact cattaggcac 8880cccaggcttt acactttatg cttccgcggc tcgtatgttg tgtggaattg tgagcggata 8940acaatttcac acaggaaaca gctatgacca tgattacgcc actagtccga ggcctcgagg 9000cggccgccaa aatagaattt gaaggagatg atttgttttc ctcccaagtg cctccactga 9060cgtttaaaat gttcctgatc atcagatgac cttcctcggt caagatggat tccggatgaa 9120attgcacacc ttctacagtg tacttcttgt gtcttacacc catgataatt ccattttcgg 9180tactcgcagt aaccttcaag caggatggta gggacgattc tgtcccggcc aatgaatggt 9240atcttgtcac agcaatacct tgcggcacgt tcttgaaaat tccacagttg tcgtgagaga 9300ttggggacgt tttaccgtgg acaatctcac cagcgtaggc aacttcacca ccaaatacgt 9360caaacatgca ttgctggccc atacagattc caaatacagg aattttccca gtaaagtacc 9420ggatacagtc tcttgaaatg ccagaatctg tctttgggtg gcctggtcca ggcgagataa 9480gcaatgtgtc gggattcaag gcggcaattt ctggaactgt aattgcatcg ttacggtaga 9540cgctcacttt ggcgccctcc tggcacaagt actcgtaaac gttccaggta aaggaatcgt 9600agttgtcaat tagaaccaca tgcttattga ttgggtttgt tgcagcgtgc acagacatat 9660ttaaatcgag gcgcgccatg ttaat 9685

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References

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