title: Massively Parallel Interrogation of the Effects of Gene Expression Levels on Fitness.
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.
authors.affiliation: 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.
authors.forename: Leeat
authors.initials: L
authors.lastname: Keren
authors.affiliation: Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Jean
authors.initials: J
authors.lastname: Hausser
authors.affiliation: Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Lotan-Pompan
authors.affiliation: Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ilya
authors.initials: I
authors.lastname: Vainberg Slutskin
authors.affiliation: Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Alisar
authors.affiliation: Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Kaminski
authors.affiliation: Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Adina
authors.initials: A
authors.lastname: Weinberger
authors.affiliation: Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
authors.affiliation: Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Milo
authors.affiliation: 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.
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
mesh_terms: D058893:DNA Barcoding, Taxonomic; D015966:Gene Expression Regulation, Fungal; D015723:Gene Library; D059647:Gene-Environment Interaction; D005800:Genes, Fungal; D056084:Genetic Fitness; D059014:High-Throughput Nucleotide Sequencing; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: D029701:Saccharomyces cerevisiae Proteins