1. Evolutionary Biology
  2. Physics of Living Systems
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Global epistasis emerges from a generic model of a complex trait

  1. Gautam Reddy  Is a corresponding author
  2. Michael M Desai  Is a corresponding author
  1. Harvard University, United States
Research Article
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Cite this article as: eLife 2021;10:e64740 doi: 10.7554/eLife.64740

Abstract

Epistasis between mutations makes 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 has 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.

Article and author information

Author details

  1. Gautam Reddy

    Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    For correspondence
    gautam_nallamala@fas.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1276-9613
  2. Michael M Desai

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    For correspondence
    mdesai@oeb.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9581-1150

Funding

Simons Foundation (NSF-Simons Center at Harvard #1764269)

  • Gautam Reddy

Simons Foundation (376196)

  • Michael M Desai

National Science Foundation (PHY-1914916)

  • Michael M Desai

National Institutes of Health (R01GM104239)

  • Michael M Desai

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Naama Barkai, Weizmann Institute of Science, Israel

Publication history

  1. Received: November 9, 2020
  2. Accepted: March 26, 2021
  3. Accepted Manuscript published: March 29, 2021 (version 1)

Copyright

© 2021, Reddy & Desai

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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