A comprehensive strategy enabling high-resolution functional analysis of the yeast genome

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Abstract
To increase the range and precision of genetic interaction studies in Saccharomyces cerevisiae, a collection of hypomorphic alleles of essential yeast genes and a highly sensitive flow cytometry–based growth competition assay are presented. Also in this issue, Yan et al. present a similar strain collection, tagged with unique bar-code identifiers, and use this collection in pooled chemical genetic screens. Functional genomic studies in Saccharomyces cerevisiae have contributed enormously to our understanding of cellular processes. Their full potential, however, has been hampered by the limited availability of reagents to systematically study essential genes and the inability to quantify the small effects of most gene deletions on growth. Here we describe the construction of a library of hypomorphic alleles of essential genes and a high-throughput growth competition assay to measure fitness with unprecedented sensitivity. These tools dramatically increase the breadth and precision with which quantitative genetic analysis can be performed in yeast. We illustrate the value of these approaches by using genetic interactions to reveal new relationships between chromatin-modifying factors and to create a functional map of the proteasome. Finally, by measuring the fitness of strains in the yeast deletion library, we addressed an enigma regarding the apparent prevalence of gene dispensability and found that most genes do contribute to growth.