A natural variant of the essential host gene MMS21 restricts the parasitic 2-micron plasmid in Saccharomyces cerevisiae
- Fred Hutchinson Cancer Research Center, United States
- Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, United States
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.
Data availability
Raw sequencing data have been deposited to the SRA database, accession PRJNA637093. De novo assemblies are in GenBank with accessions JABVXK000000000, JABVXL000000000, JABVXM000000000, JABVXN000000000, JABVXO000000000 and JABVXP000000000.
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Natural variation among Saccharomyces cerevisiae strains in resistance to 2-micron plasmidNCBI, JABVXK000000000, JABVXL000000000, JABVXM000000000, JABVXN000000000, JABVXO000000000, JABVXP000000000.
Article and author information
Author details
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
- Christian R Landry, Université Laval, Canada
Version history
- Received: August 23, 2020
- Accepted: October 15, 2020
- Accepted Manuscript published: October 16, 2020 (version 1)
- Version of Record published: November 9, 2020 (version 2)
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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A natural variant of the essential host gene MMS21 restricts the parasitic 2-micron plasmid in Saccharomyces cerevisiae
eLife 9:e62337.
https://doi.org/10.7554/eLife.62337
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