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

  1. Audrey P Gasch  Is a corresponding author
  2. James Hose
  3. Michael A Newton
  4. Maria Sardi
  5. Mun Yong
  6. Zhishi Wang
  1. University of Wisconsin-Madison, United States

Abstract

In 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 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. 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.

Article and author information

Author details

  1. 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.
  2. James Hose

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

    Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Maria Sardi

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

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

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

Reviewing Editor

  1. Duncan T Odom, University of Cambridge, United Kingdom

Publication history

  1. Received: January 14, 2016
  2. Accepted: February 26, 2016
  3. Accepted Manuscript published: March 7, 2016 (version 1)
  4. Version of Record published: March 9, 2016 (version 2)

Copyright

© 2016, Gasch 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. Audrey P Gasch
  2. James Hose
  3. Michael A Newton
  4. Maria Sardi
  5. Mun Yong
  6. Zhishi Wang
(2016)
Further support for aneuploidy tolerance in wild yeast and effects of dosage compensation on gene copy-number evolution
eLife 5:e14409.
https://doi.org/10.7554/eLife.14409
  1. Further reading

Further reading

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    James Hose, Chris Mun Yong ... Audrey P Gasch
    Research Article Updated

    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.

    1. Computational and Systems Biology
    2. Physics of Living Systems
    Spencer Farrell, Alice E Kane ... Andrew D Rutenberg
    Research Article Updated

    As an organism ages, its health-state is determined by a balance between the processes of damage and repair. Measuring these processes requires longitudinal data. We extract damage and repair transition rates from repeated observations of binary health attributes in mice and humans to explore robustness and resilience, which respectively represent resisting or recovering from damage. We assess differences in robustness and resilience using changes in damage rates and repair rates of binary health attributes. We find a conserved decline with age in robustness and resilience in mice and humans, implying that both contribute to worsening aging health – as assessed by the frailty index (FI). A decline in robustness, however, has a greater effect than a decline in resilience on the accelerated increase of the FI with age, and a greater association with reduced survival. We also find that deficits are damaged and repaired over a wide range of timescales ranging from the shortest measurement scales toward organismal lifetime timescales. We explore the effect of systemic interventions that have been shown to improve health, including the angiotensin-converting enzyme inhibitor enalapril and voluntary exercise for mice. We have also explored the correlations with household wealth for humans. We find that these interventions and factors affect both damage and repair rates, and hence robustness and resilience, in age and sex-dependent manners.