Yeast genomics: past, present, and future promise.

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