1. Evolutionary Biology
  2. Genetics and Genomics
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A natural variant of the essential host gene MMS21 restricts the parasitic 2-micron plasmid in Saccharomyces cerevisiae

  1. Michelle Hays
  2. Janet M Young
  3. Paula F Levan
  4. Harmit S Malik  Is a corresponding author
  1. Fred Hutchinson Cancer Research Center, United States
  2. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, United States
Research Article
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Cite this article as: eLife 2020;9:e62337 doi: 10.7554/eLife.62337

Abstract

Antagonistic coevolution with selfish genetic elements (SGEs) can drive evolution of host resistance. Here, we investigated host suppression of 2-micron (2m) plasmids, multicopy nuclear parasites that have co-evolved with budding yeasts. We developed SCAMPR (Single-Cell Assay for Measuring Plasmid Retention) to measure copy number heterogeneity and 2m plasmid loss in live cells. We identified three S. cerevisiae strains that lack endogenous 2m plasmids and reproducibly inhibit mitotic plasmid stability. Focusing on the Y9 ragi strain, we determined that plasmid restriction is heritable and dominant. Using bulk segregant analysis, we identified a high-confidence Quantitative Trait Locus (QTL) with a single variant of MMS21 associated with increased 2m instability. MMS21 encodes a SUMO E3 ligase and an essential component of the Smc5/6 complex, involved in sister chromatid cohesion, chromosome segregation, and DNA repair. Our analyses leverage natural variation to uncover a novel means by which budding yeasts can overcome highly successful genetic parasites.

Article and author information

Author details

  1. Michelle Hays

    Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8540-3516
  2. Janet M Young

    Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8220-8427
  3. Paula F Levan

    Basic Sciences, Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Harmit S Malik

    Division of Basic Sciences, Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    hsmalik@fhcrc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6005-0016

Funding

National Institute of General Medical Sciences (R01 GM074108)

  • Harmit S Malik

National Science Foundation (DGE-1256082)

  • Michelle Hays

National Human Genome Research Institute (5T32HG000035-20)

  • Michelle Hays

Howard Hughes Medical Institute (Investigator award)

  • Harmit S Malik

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

Reviewing Editor

  1. Christian R Landry, Université Laval, Canada

Publication history

  1. Received: August 23, 2020
  2. Accepted: October 15, 2020
  3. Accepted Manuscript published: October 16, 2020 (version 1)

Copyright

© 2020, Hays 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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