Guan Lab

Department of Computational Medicine & Bioinformatics
Wed, 11/06/2013 - 10:10 -- gl_admin
TitleA new system for comparative functional genomics of Saccharomyces yeasts.
Publication TypeJournal Article
Year of Publication2013
AuthorsCaudy AA, Guan Y, Jia Y, Hansen C, DeSevo C, Hayes AP, Agee J, Alvarez-Dominguez JR, Arellano H, Barrett D, Bauerle C, Bisaria N, Bradley PH, J Breunig S, Bush E, Cappel D, Capra E, Chen W, Clore J, Combs PA, Doucette C, Demuren O, Fellowes P, Freeman S, Frenkel E, Gadala-Maria D, Gawande R, Glass D, Grossberg S, Gupta A, Hammonds-Odie L, Hoisos A, Hsi J, Hsu Y-HHuang, Inukai S, Karczewski KJ, Ke X, Kojima M, Leachman S, Lieber D, Liebowitz A, Liu J, Liu Y, Martin T, Mena J, Mendoza R, Myhrvold C, Millian C, Pfau S, Raj S, Rich M, Rokicki J, Rounds W, Salazar M, Salesi M, Sharma R, Silverman S, Singer C, Sinha S, Staller M, Stern P, Tang H, Weeks S, Weidmann M, Wolf A, Young C, Yuan J, Crutchfield C, McClean M, Murphy CT, LlinĂ¡s M, Botstein D, Troyanskaya OG, Dunham MJ
Date Published2013 Sep

Whole-genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present a genome-wide functional characterization of a sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var. uvarum (henceforth referred to as S. bayanus), allowing us to map changes over the 20 million years that separate this organism from S. cerevisiae. We first created a suite of genetic tools to facilitate work in S. bayanus. Next, we measured the gene-expression response of S. bayanus to a diverse set of perturbations optimized using a computational approach to cover a diverse array of functionally relevant biological responses. The resulting data set reveals that gene-expression patterns are largely conserved, but significant changes may exist in regulatory networks such as carbohydrate utilization and meiosis. In addition to regulatory changes, our approach identified gene functions that have diverged. The functions of genes in core pathways are highly conserved, but we observed many changes in which genes are involved in osmotic stress, peroxisome biogenesis, and autophagy. A surprising number of genes specific to S. bayanus respond to oxidative stress, suggesting the organism may have evolved under different selection pressures than S. cerevisiae. This work expands the scope of genome-scale evolutionary studies from sequence-based analysis to rapid experimental characterization and could be adopted for functional mapping in any lineage of interest. Furthermore, our detailed characterization of S. bayanus provides a valuable resource for comparative functional genomics studies in yeast.

Alternate JournalGenetics
PubMed ID23852385
PubMed Central IDPMC3761308
Grant List8 P41 GM103533-17 / GM / NIGMS NIH HHS / United States
GM071966 / GM / NIGMS NIH HHS / United States
HG005998 / HG / NHGRI NIH HHS / United States
P50 GM071508 / GM / NIGMS NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada