Global epistasis emerges from a generic model of a complex trait

Gautam Reddy, Michael M. Desai

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Epistasis between mutations can make adaptation contingent on evolutionary history. Yet despite widespread “microscopic” epistasis between the mutations involved, microbial evolution experiments show consistent patterns of fitness increase between replicate lines. Recent work shows that this consistency is driven in part by global patterns of diminishing-returns and increasing-costs epistasis, which make mutations systematically less beneficial (or more deleterious) on fitter genetic backgrounds. However, the origin of this “global” epistasis remains unknown. Here we show that diminishing-returns and increasing-costs epistasis emerge generically as a consequence of pervasive microscopic epistasis. Our model predicts a specific quantitative relationship between the magnitude of global epistasis and the stochastic effects of microscopic epistasis, which we confirm by re-analyzing existing data. We further show that the distribution of fitness effects takes on a universal form when epistasis is widespread, and introduce a novel fitness landscape model to show how phenotypic evolution can be repeatable despite sequence-level stochasticity.

Original languageEnglish (US)
Article numbere64740
JournaleLife
Volume10
DOIs
StatePublished - Mar 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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