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Global epistasis emerges from a generic model of a complex trait

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 consist...

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Detalles Bibliográficos
Autores principales: Reddy, Gautam, Desai, Michael M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057814/
https://www.ncbi.nlm.nih.gov/pubmed/33779543
http://dx.doi.org/10.7554/eLife.64740
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author Reddy, Gautam
Desai, Michael M
author_facet Reddy, Gautam
Desai, Michael M
author_sort Reddy, Gautam
collection PubMed
description 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 reanalyzing 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.
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spelling pubmed-80578142021-04-22 Global epistasis emerges from a generic model of a complex trait Reddy, Gautam Desai, Michael M eLife Evolutionary Biology 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 reanalyzing 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. eLife Sciences Publications, Ltd 2021-03-29 /pmc/articles/PMC8057814/ /pubmed/33779543 http://dx.doi.org/10.7554/eLife.64740 Text en © 2021, Reddy and Desai https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Evolutionary Biology
Reddy, Gautam
Desai, Michael M
Global epistasis emerges from a generic model of a complex trait
title Global epistasis emerges from a generic model of a complex trait
title_full Global epistasis emerges from a generic model of a complex trait
title_fullStr Global epistasis emerges from a generic model of a complex trait
title_full_unstemmed Global epistasis emerges from a generic model of a complex trait
title_short Global epistasis emerges from a generic model of a complex trait
title_sort global epistasis emerges from a generic model of a complex trait
topic Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057814/
https://www.ncbi.nlm.nih.gov/pubmed/33779543
http://dx.doi.org/10.7554/eLife.64740
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