TY - JOUR TI - A natural variant of the essential host gene MMS21 restricts the parasitic 2-micron plasmid in Saccharomyces cerevisiae AU - Hays, Michelle AU - Young, Janet M AU - Levan, Paula F AU - Malik, Harmit S A2 - Landry, Christian R A2 - Weigel, Detlef VL - 9 PY - 2020 DA - 2020/10/16 SP - e62337 C1 - eLife 2020;9:e62337 DO - 10.7554/eLife.62337 UR - https://doi.org/10.7554/eLife.62337 AB - Antagonistic coevolution with selfish genetic elements (SGEs) can drive evolution of host resistance. Here, we investigated host suppression of 2-micron (2μ) 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 2μ plasmid loss in live cells. We identified three S. cerevisiae strains that lack endogenous 2μ 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 2μ 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. KW - genetic conflicts KW - Smc5/6 complex KW - high-copy plasmids KW - QTL KW - natural isolates KW - Smc5/6 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -