Dosage compensation can buffer copy-number variation in wild yeast

• Published in: eLife Vol. 4
• Main Authors: Hose, James, Yong, Chris Mun, Sardi, Maria, Wang, Zhishi, Newton, Michael A, Gasch, Audrey P
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 08.05.2015; eLife Sciences Publications, Ltd
• Subjects: Aneuploidy; BASIC BIOLOGICAL SCIENCES; Biological Evolution; Chromosomes; Compensation; Computational and Systems Biology; copy number variation; Deoxyribonucleic acid; DNA; Dosage compensation; Dosage Compensation, Genetic; Evolution & development; Gene amplification; Gene Dosage; gene expression; Genes, Fungal; Genetic Variation; Genomes; Genomics and Evolutionary Biology; Growth rate; Laboratories; Life Sciences & Biomedicine - Other Topics; Linear Models; Models, Genetic; Mutation; natural variation; Phenotype; Saccharomyces cerevisiae - genetics; Selection, Genetic; stress resistance; computational biology; systems biology; stress resistance; evolutionary biology; copy number variation; natural variation; aneuploidy; genomics; gene expression; S. cerevisiae
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.05462

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 10–30% 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. Evolution is driven by changes to the genes and other genetic information found in the DNA of an organism. These changes might, for example, alter the physical characteristics of the organism, or change how efficiently crucial tasks are carried out inside cells. Whatever the change, if it makes it easier for the organism to survive and reproduce, it is more likely to be passed on to future generations. DNA is organized inside cells in structures called chromosomes. Most of the cells in animals, plants, and fungi contain two copies of each chromosome. However, sometimes mistakes happen during cell division and extra copies of a chromosome—and hence the genes contained within it—may end up in a cell. These extra copies of genes might help to speed up the rate at which a species evolves, as the ‘spare’ copies are free to adapt to new roles. However, having extra copies of genes can also often be harmful, and in humans can cause genetic disorders such as Down syndrome. In the laboratory, chromosomes are commonly studied in a species of yeast called Saccharomyces cerevisiae. This species consists of several groups—or strains—that are genetically distinct from each other. Over the years, breeding the yeast for experiments has created laboratory strains that have lost some of the characteristics seen in wild strains. Earlier studies suggested that these cells fail to grow properly if they contain extra copies of chromosomes. Now, Hose et al. have studied nearly 50 wild strains of Saccharomyces cerevisiae. In these, extra copies of chromosomes are commonplace, and seemingly have no detrimental effect on growth. Instead, Hose et al. found that cells with too many copies of a gene use many of those genes less often than would be expected. This process is known as ‘dosage compensation’. This dosage compensation has not been observed in laboratory strains, in part because the extra gene copies make them sickly and hard to study. Together, the results provide examples of how dosage compensation could help new traits to evolve in a species by reducing the negative effects of duplicated genes. This knowledge may have broad application, from suggesting methods to alleviate human disorders to implicating new ways to engineer useful traits in yeast and other microbes.