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The complex underpinnings of genetic background effects

Author

Listed:
  • Martin N. Mullis

    (University of Southern California)

  • Takeshi Matsui

    (University of Southern California)

  • Rachel Schell

    (University of Southern California)

  • Ryan Foree

    (University of Southern California)

  • Ian M. Ehrenreich

    (University of Southern California)

Abstract

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.

Suggested Citation

  • Martin N. Mullis & Takeshi Matsui & Rachel Schell & Ryan Foree & Ian M. Ehrenreich, 2018. "The complex underpinnings of genetic background effects," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06023-5
    DOI: 10.1038/s41467-018-06023-5
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    Cited by:

    1. Takeshi Matsui & Martin N. Mullis & Kevin R. Roy & Joseph J. Hale & Rachel Schell & Sasha F. Levy & Ian M. Ehrenreich, 2022. "The interplay of additivity, dominance, and epistasis on fitness in a diploid yeast cross," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Solip Park & Fran Supek & Ben Lehner, 2021. "Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers," Nature Communications, Nature, vol. 12(1), pages 1-10, December.

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