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Massively Parallel Interrogation of the Effects of Gene Expression Levels on Fitness.
Keren, Leeat; Hausser, Jean; Lotan-Pompan, Maya; Vainberg Slutskin, Ilya; Alisar, Hadas; Kaminski, Sivan; Weinberger, Adina; Alon, Uri; Milo, Ron; Segal, Eran.
Afiliação
  • Keren L; Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel; Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Hausser J; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Lotan-Pompan M; Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Vainberg Slutskin I; Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Alisar H; Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Kaminski S; Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Weinberger A; Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Alon U; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Milo R; Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Segal E; Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: eran.segal@weizmann.ac.il.
Cell ; 166(5): 1282-1294.e18, 2016 Aug 25.
Article em En | MEDLINE | ID: mdl-27545349
ABSTRACT
Data of gene expression levels across individuals, cell types, and disease states is expanding, yet our understanding of how expression levels impact phenotype is limited. Here, we present a massively parallel system for assaying the effect of gene expression levels on fitness in Saccharomyces cerevisiae by systematically altering the expression level of ∼100 genes at ∼100 distinct levels spanning a 500-fold range at high resolution. We show that the relationship between expression levels and growth is gene and environment specific and provides information on the function, stoichiometry, and interactions of genes. Wild-type expression levels in some conditions are not optimal for growth, and genes whose fitness is greatly affected by small changes in expression level tend to exhibit lower cell-to-cell variability in expression. Our study addresses a fundamental gap in understanding the functional significance of gene expression regulation and offers a framework for evaluating the phenotypic effects of expression variation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saccharomyces cerevisiae / Regulação Fúngica da Expressão Gênica / Proteínas de Saccharomyces cerevisiae / Aptidão Genética / Interação Gene-Ambiente Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saccharomyces cerevisiae / Regulação Fúngica da Expressão Gênica / Proteínas de Saccharomyces cerevisiae / Aptidão Genética / Interação Gene-Ambiente Idioma: En Ano de publicação: 2016 Tipo de documento: Article