The complex underpinnings of genetic background effects

• Published in: Nature communications Vol. 9; no. 1; pp. 3548 - 10
• Main Authors: Mullis, Martin N., Matsui, Takeshi, Schell, Rachel, Foree, Ryan, Ehrenreich, Ian M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.09.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 45/23; 45/43; 45/47; 45/70; 45/77; 49; 631/208/207; 631/208/2490/1472; 64; Chromosome Mapping; Environmental effects; Epistasis; Epistasis, Genetic; Fluconazole - pharmacology; Gene Expression Regulation, Fungal; Gene Knockout Techniques; Gene-Environment Interaction; Genetic Background; Genetic crosses; Genotype; Humanities and Social Sciences; Loci; multidisciplinary; Mutants; Mutation; Neomycin - pharmacology; Progeny; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Science; Science (multidisciplinary); Yeast; Yeasts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06023-5

Genetic interactions between mutations and standing polymorphisms can cause mutations to show distinct phenotypic effects in different individuals. To characterize the genetic architecture of these so-called background effects, we genotype 1411 wild-type and mutant yeast cross progeny and measure their growth in 10 environments. Using these data, we map 1086 interactions between segregating loci and 7 different gene knockouts. Each knockout exhibits between 73 and 543 interactions, with 89% of all interactions involving higher-order epistasis between a knockout and multiple loci. Identified loci interact with as few as one knockout and as many as all seven knockouts. In mutants, loci interacting with fewer and more knockouts tend to show enhanced and reduced phenotypic effects, respectively. Cross–environment analysis reveals that most interactions between the knockouts and segregating loci also involve the environment. These results illustrate the complicated interactions between mutations, standing polymorphisms, and the environment that cause background effects. Mutations often show distinct phenotypic effects across different genetic backgrounds. Here the authors describe the genetic basis of these so-called background effects using data on genotype and growth in 10 environments from 1411 segregants from a cross of two strains of budding yeast.