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Gene essentiality is typically determined by assessing the viability of the corresponding mutant cells, but this definition fails to account for the ability of cells to adaptively evolve to genetic perturbations. Here, we performed a stringent screen to assess the degree to which Saccharomyces cerevisiae cells can survive the deletion of ~1,000 individual "essential" genes and found that ~9% of these genetic perturbations could in fact be overcome by adaptive evolution. Our analyses uncovered a genome-wide gradient of gene essentiality, with certain essential cellular functions being more "evolvable" than others. Ploidy changes were prevalent among the evolved mutant strains, and aneuploidy of a specific chromosome was adaptive for a class of evolvable nucleoporin mutants. These data justify a quantitative redefinition of gene essentiality that incorporates both viability and evolvability of the corresponding mutant cells and will enable selection of therapeutic targets associated with lower risk of emergence of drug resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

Citation

Gaowen Liu, Mei Yun Jacy Yong, Marina Yurieva, Kandhadayar Gopalan Srinivasan, Jaron Liu, John Soon Yew Lim, Michael Poidinger, Graham Daniel Wright, Francesca Zolezzi, Hyungwon Choi, Norman Pavelka, Giulia Rancati. Gene Essentiality Is a Quantitative Property Linked to Cellular Evolvability. Cell. 2015 Dec 3;163(6):1388-99

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PMID: 26627736

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