Functional profiling of the Saccharomyces cerevisiae genome

Abstract

Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics.

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Affiliated Institutions

• University of California, Berkeley US
• Goethe University Frankfurt DE
• KU Leuven BE
• Heinrich Heine University Düsseldorf DE
• Université Libre de Bruxelles BE
• Johns Hopkins Medicine US
• UCLouvain BE
• Frederick National Laboratory for Cancer Research US
• Stanford University US
• Universidad de Salamanca ES
• Yale University US
• University of Padua IT
• National Cancer Institute US
• Rosetta Stone (United States) US
• McGill University CA
• Aberystwyth University GB
• University of Basel CH
• Johns Hopkins University US
• Washington University in St. Louis US
• Concordia University CA
• Center for Cancer Research US
• University of Wales GB

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