1. Chromosomes and Gene Expression
  2. Genetics and Genomics

Dosage compensation can buffer copy-number variation in wild yeast

  1. James Hose
  2. Chris Mun Yong
  3. Maria Sardi
  4. Zhishi Wang
  5. Michael A Newton
  6. Audrey P Gasch  Is a corresponding author
  1. University of Wisconsin-Madison, United States
https://doi.org/10.7554/eLife.05462
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  1. James Hose
  2. Chris Mun Yong
  3. Maria Sardi
  4. Zhishi Wang
  5. Michael A Newton
  6. Audrey P Gasch
(2015)
Dosage compensation can buffer copy-number variation in wild yeast
eLife 4:e05462.
https://doi.org/10.7554/eLife.05462
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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.

Article and author information

Author details

  1. James Hose

    Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Chris Mun Yong

    Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Maria Sardi

    Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Zhishi Wang

    Department of Statistics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Michael A Newton

    Department of Statistics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Audrey P Gasch

    Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
    For correspondence
    agasch@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Duncan T Odom, Cancer Research UK Cambridge Institute, United Kingdom

Version history

  1. Received: November 3, 2014
  2. Accepted: May 7, 2015
  3. Accepted Manuscript published: May 8, 2015 (version 1)
  4. Version of Record published: May 29, 2015 (version 2)
  5. Version of Record updated: March 23, 2016 (version 3)

Copyright

© 2015, Hose et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. James Hose
  2. Chris Mun Yong
  3. Maria Sardi
  4. Zhishi Wang
  5. Michael A Newton
  6. Audrey P Gasch
(2015)
Dosage compensation can buffer copy-number variation in wild yeast
eLife 4:e05462.
https://doi.org/10.7554/eLife.05462

Share this article

https://doi.org/10.7554/eLife.05462

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Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression

    No current evidence for widespread dosage compensation in S. cerevisiae

    Eduardo M Torres, Michael Springer, Angelika Amon
    Research Article

    Previous studies of laboratory strains of budding yeast had shown that when gene copy number is altered experimentally, RNA levels generally scale accordingly. This is true when the copy number of individual genes or entire chromosomes is altered. In a recent study, Hose et al. (2015) reported that this tight correlation between gene copy number and RNA levels is not observed in recently isolated wild Saccharomyces cerevisiae variants. To understand the origins of this proposed difference in gene expression regulation between natural variants and laboratory strains of S. cerevisiae, we evaluated the karyotype and gene expression studies performed by Hose et al. on wild S. cerevisiae strains. In contrast to the results of Hose et al., our reexamination of their data revealed a tight correlation between gene copy number and gene expression. We conclude that widespread dosage compensation occurs neither in laboratory strains nor in natural variants of S. cerevisiae.

    1. Computational and Systems Biology
    2. Evolutionary Biology

    Further support for aneuploidy tolerance in wild yeast and effects of dosage compensation on gene copy-number evolution

    Audrey P Gasch, James Hose ... Zhishi Wang
    Short Report Updated

    In our prior work by Hose et al., we performed a genome-sequencing survey and reported that aneuploidy was frequently observed in wild strains of S. cerevisiae. We also profiled transcriptome abundance in naturally aneuploid isolates compared to isogenic euploid controls and found that 10–30% of amplified genes, depending on the strain and affected chromosome, show lower-than-expected expression compared to gene copy number. In Hose et al., we argued that this gene group is enriched for genes subject to one or more modes of dosage compensation, where mRNA abundance is decreased in response to higher dosage of that gene. A recent manuscript by Torres et al. refutes our prior work. Here, we provide a response to Torres et al., along with additional analysis and controls to support our original conclusions. We maintain that aneuploidy is well tolerated in the wild strains of S. cerevisiae that we studied and that the group of genes enriched for those subject to dosage compensation show unique evolutionary signatures.