PT - JOURNAL ARTICLE AU - Rachel Schell AU - Joseph J. Hale AU - Martin N. Mullis AU - Takeshi Matsui AU - Ryan Foree AU - Ian M. Ehrenreich TI - Genetic basis of a spontaneous mutation’s expressivity AID - 10.1101/2020.04.03.024547 DP - 2021 Jan 01 TA - bioRxiv PG - 2020.04.03.024547 4099 - http://biorxiv.org/content/early/2021/08/02/2020.04.03.024547.short 4100 - http://biorxiv.org/content/early/2021/08/02/2020.04.03.024547.full AB - Genetic background often influences the phenotypic consequences of mutations, resulting in variable expressivity. How standing genetic variants collectively cause this phenomenon is not fully understood. Here, we comprehensively identify loci in a budding yeast cross that impact the growth of individuals carrying a spontaneous missense mutation in the nuclear-encoded mitochondrial ribosomal gene MRP20. Initial results suggested that a single large effect locus influences the mutation’s expressivity, with one allele causing inviability in mutants. However, further experiments revealed this simplicity was an illusion. In fact, many additional loci shape the mutation’s expressivity, collectively leading to a wide spectrum of mutational responses. These results exemplify how complex combinations of alleles can produce a diversity of qualitative and quantitative responses to the same mutation.Competing Interest StatementThe authors have declared no competing interest.