Effects of Synonymous Mutations beyond Codon Bias: The Evidence for Adaptive Synonymous Substitutions from Microbial Evolution Experiments
Synonymous mutations are often assumed to be neutral with respect to fitness because they do not alter the encoded amino acid and so cannot be “seen” by natural selection. Yet a growing body of evidence suggests that synonymous mutations can have fitness effects that drive adaptive evolution through...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410137/ https://www.ncbi.nlm.nih.gov/pubmed/34132772 http://dx.doi.org/10.1093/gbe/evab141 |
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author | Bailey, Susan F Alonso Morales, Luz Angela Kassen, Rees |
author_facet | Bailey, Susan F Alonso Morales, Luz Angela Kassen, Rees |
author_sort | Bailey, Susan F |
collection | PubMed |
description | Synonymous mutations are often assumed to be neutral with respect to fitness because they do not alter the encoded amino acid and so cannot be “seen” by natural selection. Yet a growing body of evidence suggests that synonymous mutations can have fitness effects that drive adaptive evolution through their impacts on gene expression and protein folding. Here, we review what microbial experiments have taught us about the contribution of synonymous mutations to adaptation. A survey of site-directed mutagenesis experiments reveals the distributions of fitness effects for nonsynonymous and synonymous mutations are more similar, especially for beneficial mutations, than expected if all synonymous mutations were neutral, suggesting they should drive adaptive evolution more often than is typically observed. A review of experimental evolution studies where synonymous mutations have contributed to adaptation shows they can impact fitness through a range of mechanisms including the creation of illicit RNA polymerase binding sites impacting transcription and changes to mRNA folding stability that modulate translation. We suggest that clonal interference in evolving microbial populations may be the reason synonymous mutations play a smaller role in adaptive evolution than expected based on their observed fitness effects. We finish by discussing the impacts of falsely assuming synonymous mutations are neutral and discuss directions for future work exploring the role of synonymous mutations in adaptive evolution. |
format | Online Article Text |
id | pubmed-8410137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-84101372021-09-02 Effects of Synonymous Mutations beyond Codon Bias: The Evidence for Adaptive Synonymous Substitutions from Microbial Evolution Experiments Bailey, Susan F Alonso Morales, Luz Angela Kassen, Rees Genome Biol Evol Review Synonymous mutations are often assumed to be neutral with respect to fitness because they do not alter the encoded amino acid and so cannot be “seen” by natural selection. Yet a growing body of evidence suggests that synonymous mutations can have fitness effects that drive adaptive evolution through their impacts on gene expression and protein folding. Here, we review what microbial experiments have taught us about the contribution of synonymous mutations to adaptation. A survey of site-directed mutagenesis experiments reveals the distributions of fitness effects for nonsynonymous and synonymous mutations are more similar, especially for beneficial mutations, than expected if all synonymous mutations were neutral, suggesting they should drive adaptive evolution more often than is typically observed. A review of experimental evolution studies where synonymous mutations have contributed to adaptation shows they can impact fitness through a range of mechanisms including the creation of illicit RNA polymerase binding sites impacting transcription and changes to mRNA folding stability that modulate translation. We suggest that clonal interference in evolving microbial populations may be the reason synonymous mutations play a smaller role in adaptive evolution than expected based on their observed fitness effects. We finish by discussing the impacts of falsely assuming synonymous mutations are neutral and discuss directions for future work exploring the role of synonymous mutations in adaptive evolution. Oxford University Press 2021-06-16 /pmc/articles/PMC8410137/ /pubmed/34132772 http://dx.doi.org/10.1093/gbe/evab141 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Review Bailey, Susan F Alonso Morales, Luz Angela Kassen, Rees Effects of Synonymous Mutations beyond Codon Bias: The Evidence for Adaptive Synonymous Substitutions from Microbial Evolution Experiments |
title | Effects of Synonymous Mutations beyond Codon Bias: The Evidence for Adaptive Synonymous Substitutions from Microbial Evolution Experiments |
title_full | Effects of Synonymous Mutations beyond Codon Bias: The Evidence for Adaptive Synonymous Substitutions from Microbial Evolution Experiments |
title_fullStr | Effects of Synonymous Mutations beyond Codon Bias: The Evidence for Adaptive Synonymous Substitutions from Microbial Evolution Experiments |
title_full_unstemmed | Effects of Synonymous Mutations beyond Codon Bias: The Evidence for Adaptive Synonymous Substitutions from Microbial Evolution Experiments |
title_short | Effects of Synonymous Mutations beyond Codon Bias: The Evidence for Adaptive Synonymous Substitutions from Microbial Evolution Experiments |
title_sort | effects of synonymous mutations beyond codon bias: the evidence for adaptive synonymous substitutions from microbial evolution experiments |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410137/ https://www.ncbi.nlm.nih.gov/pubmed/34132772 http://dx.doi.org/10.1093/gbe/evab141 |
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