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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 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.

Publication Date:
Research Org.:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)
OSTI Identifier:
1227971
Alternate Identifier(s):
OSTI ID: 1227972; OSTI ID: 1628830
Grant/Contract Number:  
FC02-07ER64494; R01GM083989; R21HG006568
Resource Type:
Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Name: eLife Journal Volume: 4; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Life Sciences & Biomedicine - Other Topics

Citation Formats

Dosage compensation can buffer copy-number variation in wild yeast. United States: N. p., 2015. Web. doi:10.7554/eLife.05462.
Dosage compensation can buffer copy-number variation in wild yeast. United States. https://doi.org/10.7554/eLife.05462
Fri . "Dosage compensation can buffer copy-number variation in wild yeast". United States. https://doi.org/10.7554/eLife.05462.
@article{osti_1227971,
title = {Dosage compensation can buffer copy-number variation in wild yeast},
author = {None, None},
abstractNote = {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.},
doi = {10.7554/eLife.05462},
journal = {eLife},
number = ,
volume = 4,
place = {United States},
year = {Fri May 08 00:00:00 EDT 2015},
month = {Fri May 08 00:00:00 EDT 2015}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.7554/eLife.05462

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Cited by: 87 works
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Figures / Tables:

Figure 1 Figure 1: Aneuploidy is common in non-laboratory strains. (A) Relative DNA copy (log2 (RPKM)) per gene (rows) across each of the 16 chromosomes for 47 sequenced strains (columns). Strains with 1.5x (gray text) or 2x (blue text) chromosomal copy per haploid genome are annotated by name. (B) Growth rates ofmore » aneuploid strains normalized to the niche-specific growth rate (see ‘Materials and methods’) plotted against the additional DNA content in each strain. (C) Haploid strains with a duplication of Chr 8 (labeled as ‘disome’) were selected from euploid parents (labeled as ‘monosome’) including the S288c-derived DBY7286, derived vineyard strain KCY40, and a haploid derivative of oak strain YPS163, see ‘Materials and methods’. Doubling times in YPD medium represent the average of four biological replicates; the average difference (‘dif’) in growth rate is indicated. An asterisk represents statistically significant differences in doubling time (p < 6e-4, T-test).« less

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