1. Genetics and Genomics

Natural variation in the consequences of gene overexpression and its implications for evolutionary trajectories

  1. DeElegant Robinson
  2. Mike Place
  3. James Hose
  4. Adam Jochem
  5. Audrey P Gasch  Is a corresponding author
  1. University of Wisconsin-Madison, United States
https://doi.org/10.7554/eLife.70564
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  1. DeElegant Robinson
  2. Mike Place
  3. James Hose
  4. Adam Jochem
  5. Audrey P Gasch
(2021)
Natural variation in the consequences of gene overexpression and its implications for evolutionary trajectories
eLife 10:e70564.
https://doi.org/10.7554/eLife.70564
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Abstract

Copy number variation (CNV) through gene or chromosome amplification provides a route for rapid phenotypic variation and supports long-term evolution of gene functions. Although the evolutionary importance of CNV is known, little is understood about how genetic background influences CNV tolerance. Here, we measured fitness costs of over 4,000 over-expressed genes in 15 Saccharomyces cerevisiae strains representing different lineages, to explore natural variation in tolerating gene overexpression (OE). Strain-specific effects dominated the fitness costs of gene OE. We report global differences in the consequences of gene OE, independent of the amplified gene, as well as gene-specific effects that were dependent on the genetic background. Natural variation in the response to gene OE could be explained by several models, including strain-specific physiological differences, resource limitations, and regulatory sensitivities. This work provides new insight on how genetic background influences tolerance to gene amplification and the evolutionary trajectories accessible to different backgrounds.

Data availability

Barcode sequencing data are available in the Short Read Archive under accession number GSE171586. RNA-Seq data are available in GEO accession number GSE171585.

The following data sets were generated

Article and author information

Author details

  1. DeElegant Robinson

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Mike Place

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. James Hose

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Adam Jochem

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Audrey P Gasch

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    For correspondence
    agasch@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8182-257X

Funding

National Cancer Institute (R01CA229532)

  • James Hose
  • Adam Jochem
  • Audrey P Gasch

U.S. Department of Energy (DE-SC0018409)

  • Mike Place
  • Audrey P Gasch

National Institutes of Health (GT32GM007133)

  • DeElegant Robinson

National Human Genome Research Institute (5T32HG002760)

  • DeElegant Robinson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2021, Robinson 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. DeElegant Robinson
  2. Mike Place
  3. James Hose
  4. Adam Jochem
  5. Audrey P Gasch
(2021)
Natural variation in the consequences of gene overexpression and its implications for evolutionary trajectories
eLife 10:e70564.
https://doi.org/10.7554/eLife.70564

Share this article

https://doi.org/10.7554/eLife.70564

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