Gene Essentiality Is a Quantitative Property Linked to Cellular Evolvability

Gene Essentiality Is a Quantitative Property Linked to Cellular Evolvability
Title:
Gene Essentiality Is a Quantitative Property Linked to Cellular Evolvability
Other Titles:
Cell
Publication Date:
25 November 2015
Citation:
Gene Essentiality Is a Quantitative Property Linked to Cellular Evolvability Liu, Gaowen et al. Cell, Volume 163, Issue 6, 1388 - 1399
Abstract:
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.
License type:
PublisherCopyrights
Funding Info:
G.R. is supported by A∗STAR Investigatorship award 1437a00119. N.P. is supported by A∗STAR Investigatorship award 1437a00117. H.C. is supported by a Singapore Ministry of Education Tier 2 Grant R-608-000-088-112
Description:
The full paper is available for download at the publisher's URL: https://doi.org/10.1016/j.cell.2015.10.069
ISSN:
0092-8674
1097-4172
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