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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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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. |
format | Online Article Text |
id | pubmed-8057814 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT reddygautam globalepistasisemergesfromagenericmodelofacomplextrait AT desaimichaelm globalepistasisemergesfromagenericmodelofacomplextrait |