A natural variant of the essential host gene MMS21 restricts the parasitic 2-micron plasmid in Saccharomyces cerevisiae

Abstract
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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.

The following data sets were generated

1. Hays M
2. Young JM
3. Levan PF
4. Malik HS
(2020) Natural variation among Saccharomyces cerevisiae strains in resistance to 2-micron plasmid
NCBI, PRJNA637093.

http://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA637093
1. Hays M
2. Young JM
3. Levan PF
4. Malik HS
(2020) Natural variation among Saccharomyces cerevisiae strains in resistance to 2-micron plasmid
NCBI, JABVXK000000000, JABVXL000000000, JABVXM000000000, JABVXN000000000, JABVXO000000000, JABVXP000000000.

https://www.ncbi.nlm.nih.gov/genbank/

The following previously published data sets were used

1. Giltae Song
2. Stanford University
(2014) Saccharomyces cerevisiae strain genomes commonly used in laboratories
SRR1569895.

https://www.ncbi.nlm.nih.gov/sra/SRR1569895

Article and author information

Author details

Michelle Hays

Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8540-3516
Janet M Young

Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8220-8427
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.
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.

"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.

Copyright

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.