title: Dosage compensation can buffer copy-number variation in wild yeast.
abstract: Aneuploidy is linked to myriad diseases but also facilitates organismal evolution. It remains unclear how cells overcome the deleterious effects of aneuploidy until new phenotypes evolve. Although laboratory strains are extremely sensitive to aneuploidy, we show here that aneuploidy is common in wild yeast isolates, which show lower-than-expected expression at many amplified genes. We generated diploid strain panels in which cells carried two, three, or four copies of the affected chromosomes, to show that gene-dosage compensation functions at >30% of amplified genes. Genes subject to dosage compensation are under higher expression constraint in wild populations-but they show elevated rates of gene amplification, suggesting that copy-number variation is buffered at these genes. We find that aneuploidy provides a clear ecological advantage to oak strain YPS1009, by amplifying a causal gene that escapes dosage compensation. Our work presents a model in which dosage compensation buffers gene amplification through aneuploidy to provide a natural, but likely transient, route to rapid phenotypic evolution.
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States.
authors.forename: James
authors.initials: J
authors.lastname: Hose
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States.
authors.forename: Chris Mun
authors.initials: CM
authors.lastname: Yong
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Sardi
authors.affiliation: Department of Statistics, University of Wisconsin-Madison, Madison, United States.
authors.forename: Zhishi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Statistics, University of Wisconsin-Madison, Madison, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Newton
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States.
authors.forename: Audrey P
authors.initials: AP
authors.lastname: Gasch
mesh_terms: D000782:Aneuploidy; D005075:Biological Evolution; D004303:Dosage Compensation, Genetic; D018628:Gene Dosage; D005800:Genes, Fungal; D014644:Genetic Variation; D016014:Linear Models; D008957:Models, Genetic; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D012641:Selection, Genetic
keywords: S. cerevisiae; aneuploidy; computational biology; copy number variation; evolutionary biology; gene expression; genomics; natural variation; stress resistance; systems biology