3
In most respects, 6 years is a fairly brief period of time – but to the field of yeast genomics, 6 years has represented a literal and figurative lifetime. For all practical purposes, yeast genomics was born in 1996, when a consortium of 16 laboratories determined the complete genomic DNA sequence of Saccharomyces cerevisiae strain S288c (Goffeau et al. 1996). As the first eucaryotic genome to be sequenced in its entirety, and only the third genome of a free living organism to be decoded, this 13-megabase genomic sequence represented an obvious landmark in eucaryotic molecular biology. Initial analysis of the yeast genome revealed approximately 6,200 genes (as defined by open reading frames greater than 100 codons in length; Mewes et al. 1997); two thirds of these genes had not been characterized previously, suggesting that much work lay ahead before a full understanding of yeast biolo- gy could even be considered. In fact, achievement of this sequencing milestone was only the beginning. The ensuing years have witnessed the emergence of many genome and proteome projects analyzing the func- tion, regulation and replication of yeast genes (Table 1). These projects have not only generated novel methodol- ogies for the large-scale analysis of genes and proteins, but have also provided a wealth of information describ- ing yeast biology. Information now exists for over 90% of all annotated yeast open reading frames, and now two- thirds of yeast genes have been pursued by individual re- searchers to provide some level of characterization – at least enough to give them a name. Since one-third of yeast proteins are predicted to be homologous to proteins from multicellular organisms, and another third exhibit some similarity to their mammalian counterparts, this wealth of information is of high interest across all spe- cies. In addition, over 150 genes implicated in human disease have homologs in yeast, thereby providing more direct information about the genetic basis of human pa- thologies. Finally, following advances spawned by the yeast genomic projects, similar projects have emerged for the analysis of genes in other organisms. Some of the earliest genomics projects described ap- plications of transposon mutagenesis for the analysis of gene expression, protein localization and gene disruption phenotypes (Burns et al. 1994; Ross-MacDonald et al. 1999), and the development of microarrays for the analy- sis of RNA expression (Pease et al. 1994; Schena et al. 1995). Gene expression studies describing RNA expres- sion profiling and direct global methods for the analysis of transcription factor targets are reviewed in the chapter by Horak et al. Fundamental to the field of eucaryotic cell biology is an understanding of the mechanisms by which eucaryotic cells handle environmental stresses, such as starvation and other stress responses. Recent studies have provided significant insights into this process as de- scribed by Gasch and Werner-Washburne. A project to systematically disrupt genes has recently been completed; this work possesses enormous potential not only for the characterization of yeast genes, but also for discovery of the mechanism of action of drugs. These topics are re- viewed in Winzeler and Hughes, respectively. Whereas the field of genomics has been flourishing for several years, the field of proteomics is just beginning. The first large scale projects to study protein-protein interac- tions using two hybrid studies and affinity purifica- tion/mass spectrometry methods have recently been de- scribed, providing information concerning over 6,000 po- tential protein interactions (Gavin et al. 2002; Ho et al. 2002; Ito et al. 2000; Uetz et al. 2000). Methods for the biochemical analysis of gene products using collections of overexpressed fusion proteins and either pooling strategies (Martzen et al. 1999) or “proteome chips” (MacBeath and Schreiber 2000; Zhu et al. 2000, 2001) have been de- scribed. Analysis of what proteins are expressed and where they are expressed is currently ongoing. The subcellular lo- calization of most of a eucaryotic proteome has just been completed (Kumar et al. 2002a), and mass spectrometry methods for the detection of over 1,000 proteins have been established (Washburn et al. 2001), providing some of the M. Snyder ( ) · A. Kumar Yale University, Department of Biology, 266 Whitney Ave., New Haven, CT 06520-8103, USA e-mail: [email protected] Funct Integr Genomics (2002) 2:135–137 DOI 10.1007/s10142-002-0064-4 EDITORIAL Michael Snyder · Anuj Kumar Yeast genomics: past, present, and future promise Received: 17 May 2002 / Accepted: 28 May 2002 / Published online: 20 June 2002 © Springer-Verlag 2002

Yeast genomics: past, present, and future promise

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Page 1: Yeast genomics: past, present, and future promise

In most respects, 6 years is a fairly brief period of time –but to the field of yeast genomics, 6 years has representeda literal and figurative lifetime. For all practical purposes,yeast genomics was born in 1996, when a consortium of16 laboratories determined the complete genomic DNAsequence of Saccharomyces cerevisiae strain S288c(Goffeau et al. 1996). As the first eucaryotic genome tobe sequenced in its entirety, and only the third genome ofa free living organism to be decoded, this 13-megabasegenomic sequence represented an obvious landmark ineucaryotic molecular biology. Initial analysis of the yeastgenome revealed approximately 6,200 genes (as definedby open reading frames greater than 100 codons inlength; Mewes et al. 1997); two thirds of these genes hadnot been characterized previously, suggesting that muchwork lay ahead before a full understanding of yeast biolo-gy could even be considered. In fact, achievement of thissequencing milestone was only the beginning.

The ensuing years have witnessed the emergence ofmany genome and proteome projects analyzing the func-tion, regulation and replication of yeast genes (Table 1).These projects have not only generated novel methodol-ogies for the large-scale analysis of genes and proteins,but have also provided a wealth of information describ-ing yeast biology. Information now exists for over 90%of all annotated yeast open reading frames, and now two-thirds of yeast genes have been pursued by individual re-searchers to provide some level of characterization – atleast enough to give them a name. Since one-third ofyeast proteins are predicted to be homologous to proteinsfrom multicellular organisms, and another third exhibitsome similarity to their mammalian counterparts, thiswealth of information is of high interest across all spe-cies. In addition, over 150 genes implicated in humandisease have homologs in yeast, thereby providing moredirect information about the genetic basis of human pa-

thologies. Finally, following advances spawned by theyeast genomic projects, similar projects have emergedfor the analysis of genes in other organisms.

Some of the earliest genomics projects described ap-plications of transposon mutagenesis for the analysis ofgene expression, protein localization and gene disruptionphenotypes (Burns et al. 1994; Ross-MacDonald et al.1999), and the development of microarrays for the analy-sis of RNA expression (Pease et al. 1994; Schena et al.1995). Gene expression studies describing RNA expres-sion profiling and direct global methods for the analysisof transcription factor targets are reviewed in the chapterby Horak et al. Fundamental to the field of eucaryotic cellbiology is an understanding of the mechanisms by whicheucaryotic cells handle environmental stresses, such asstarvation and other stress responses. Recent studies haveprovided significant insights into this process as de-scribed by Gasch and Werner-Washburne. A project tosystematically disrupt genes has recently been completed;this work possesses enormous potential not only for thecharacterization of yeast genes, but also for discovery ofthe mechanism of action of drugs. These topics are re-viewed in Winzeler and Hughes, respectively.

Whereas the field of genomics has been flourishing forseveral years, the field of proteomics is just beginning. Thefirst large scale projects to study protein-protein interac-tions using two hybrid studies and affinity purifica-tion/mass spectrometry methods have recently been de-scribed, providing information concerning over 6,000 po-tential protein interactions (Gavin et al. 2002; Ho et al.2002; Ito et al. 2000; Uetz et al. 2000). Methods for thebiochemical analysis of gene products using collections ofoverexpressed fusion proteins and either pooling strategies(Martzen et al. 1999) or “proteome chips” (MacBeath andSchreiber 2000; Zhu et al. 2000, 2001) have been de-scribed. Analysis of what proteins are expressed and wherethey are expressed is currently ongoing. The subcellular lo-calization of most of a eucaryotic proteome has just beencompleted (Kumar et al. 2002a), and mass spectrometrymethods for the detection of over 1,000 proteins have beenestablished (Washburn et al. 2001), providing some of the

M. Snyder (✉ ) · A. KumarYale University, Department of Biology, 266 Whitney Ave.,New Haven, CT 06520-8103, USAe-mail: [email protected]

Funct Integr Genomics (2002) 2:135–137DOI 10.1007/s10142-002-0064-4

E D I T O R I A L

Michael Snyder · Anuj Kumar

Yeast genomics: past, present, and future promise

Received: 17 May 2002 / Accepted: 28 May 2002 / Published online: 20 June 2002© Springer-Verlag 2002

Page 2: Yeast genomics: past, present, and future promise

first methods for rapid protein profiling. This latter subjectis reviewed by Goodlett. One area of high importance toyeast and other organisms are the membrane proteins; thesubject of classification of yeast transporters and othermembrane proteins according to their phylogenetic rela-tionships is reviewed by De Hertogh et al.

To keep pace with these large-scale studies, databaseshave proliferated just as quickly as the large-scale “om-ics” projects themselves. There are several broad databas-es that provide many types of information about specificyeast genes and proteins (Ball et al. 2001; Costanzo et al.2001; Mewes et al. 2002) as well as a number of special-ized databases that focus on one or several types of infor-mation (Kumar et al. 2002b). Given that the fields offunctional genomics and proteomics are very much in anascent phase, the wealth of information that already ex-ists will be dwarfed by the information that will emergein the next few years. In the very near future, the chal-lenge for most researchers will be to extract and analyzethe relevant information from the different databases fordesigning their own experiments and scientific studies.

The ensuing manuscripts review many highlights fromthe “genome and proteome” analysis era. Since this erahas only just begun, we can expect these studies to pro-vide a small inkling of what is to come, not only for thebudding yeast, but also for many other organisms as well.

References

Ball C, Jin H, Sherlock G, Weng S, Matese JC, Andrada R, Binkley G, Dolinski K, Dwight SS, Harris MA, Issel-Tarver L,Schroeder M, Botstein D, Cherry JM (2001) SaccharomycesGenome Database provides tools to survey gene expressionand functional analysis data. Nucleic Acids Res 29:80–81

Burns N, Grimwade B, Ross-Macdonald PB, Choi E-Y, Finberg K,Roeder GS, Snyder M (1994) Large-scale characterization ofgene expression, protein localization and gene disruption inSaccharomyces cerevisiae. Genes Dev 8:1087–1105

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Table 1 Examples of yeast genomic and proteomic projects

Research area/data type Approach Example references

Gene expression Microarray analysis (Cho et al. 1998; DeRisi et al. 1997; Roberts et al. 2000)

SAGE (Velculescu et al. 1997)Transposon tagging/mutagenesis (Burns et al. 1994; Ross-MacDonald et al. 1999)

Transcription factor Chromatin IP/DNA microarrays (Iyer et al. 2001; Ren et al. 2000)target identificationGenetic interactions Systematic genome- (Tong et al. 2001)

wide synthetic lethal screeningGene disruption Systematic gene deletions (Winzeler et al. 1999)

Transposon tagging/mutagenes (Burns et al. 1994; Ross-MacDonald et al. 1999)Protein localization Transposon tagging/directed cloning (Kumar et al. 2002a; Ross-MacDonald et al. 1999;

Burns et al. 1994)Protein biochemistry Biochemical genomics (Martzen et al. 1999)

Protein microarrays (Zhu et al. 2000, 2001; MacBeath and Schreiber 2000)

Protein-protein interactions Two-hybrid methods (Uetz et al. 2000; Ito et al. 2000)Co-IP/mass spectrometry (Gavin et al. 2002; Ho et al. 2002)Protein microarrays (MacBeath and Schreiber 2000;

Zhu et al. 2000, 2001)Protein profiling Two-dimensional gel analysis (Futcher et al. 1999)

Mass spectrometry (Gygi et al. 1999; Link et al. 1999; Washburn et al. 2001)

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Iyer VR, Horak CE, Scafe CS, Botstein D, Snyder M, Brown PO(2001) Genomic binding sites of the yeast cell-cycle transcrip-tion factors SBF and MBF. Nature 409:533–538

Kumar A, Agarwal S, Heyman JA, Matson S, Heidtman M, Picci-rillo S, Umansky L, Drawid A, Jansen R, Liu Y, Cheung K-H,Miller P, Gerstein M, Roeder GS, Snyder M (2002a) Subcellu-lar localization of the yeast proteome. Genes Dev 16:707–719

Kumar A, Cheung K-H, Tosches N, Masiar P, Liu Y, Miller P, Sny-der M (2002b) The TRIPLES database: a community resourcefor yeast molecular biology. Nucleic Acids Res 30:73–75

Link AJ, Eng J, Schieltz DM, Carmack E, Mize GJ, Morris DR,Garvik BM, Yates JR III (1999) Direct analysis of protein com-plexes using mass spectrometry. Nat Biotechnol 17:676–682

MacBeath G, Schreiber SL (2000) Printing proteins as microar-rays for high-throughput function determination. Science 289:1760–1763

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Boone C, Friend SH (2000) Signaling and circuitry of multipleMAPK pathways revealed by a matrix of global gene expres-sion profiles. Science 287:873–878

Ross-MacDonald P, Coelho PSR, Roemer T, Agarwal S, Kumar A,Jansen R, Cheung K-H, Sheehan A, Symoniatis D, Umansky L,Heidtman M, Nelson FK, Iwasaki H, Hager K, Gerstein M, Miller P, Roeder GS, Snyder M (1999) Large-scale analysis ofthe yeast genome by transposon tagging and gene disruption.Nature 402:413–418

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Uetz P, Giot L, Cagney G, Mansfield TA, Judson RS, Knight JR,Lockshon D, Narayan V, Srinivasan M, Pochart P, Qureshi-Emili A, Li Y, Godwin B, Conover D, Kalbfleisch T, Vijyad-amodar G, Yang M, Johnston M, Fields S, Rothberg JM(2000) A comprehensive analysis of protein-protein interac-tions in Saccharomyces cerevisiae. Nature 403:623–627

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Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K,Andre B, Bangham R, Benito R, Boeke JD, Bussey H, Chu AM,Connelly C, Davis K, Dietrich FS, Dow S, Bakkoury M-E,Foury F, Friend SH, Gentalen E, Giaever G, Hegemann JH,Jones TW, Laub M, Liao H, Liebundguth N, Lockhart DJ, Lucau-Danila A, Lussier M, M'Rabet N, Menard P, Mittmann M, Pai C,Rebischung C, Revuelta JL, Riles L, Roberts CJ, Ross-Macdon-ald P, Scherens B, Snyder M, Sookhai-Mahadeo S, Storms RK,Veronneau S, Voet M, Volkaert G, Ward TR, Wysocki R, Yen GS,Yu K, Zimmerman K, Philippsen P, Johnston M, Davis RW(1999) Functional characterization of the S. cerevisiae genome bygene deletion and parallel analysis. Science 285:901–906

Zhu H, Klemic JF, Chang S, Bertone P, Casamayor A, Klemic KG,Smith D, Gerstein M, Reed MA, Snyder M (2000) Analysis ofyeast protein kinases using protein chips. Nat Genet 26:283–289

Zhu H, Bilgin M, Bangham R, Hall D, Casamayor A, Bertone P,Lan N, Jansen R, Bidlingmaier S, Houfek T, Mitchell T, Miller P,Dean RA, Gerstein M, Snyder M (2001) Global analysis of pro-tein activities using proteome chips. Science 293:2101–2105

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