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...

Descripción completa

Detalles Bibliográficos
Autores principales: Bailey, Susan F, Alonso Morales, Luz Angela, Kassen, Rees
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
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
_version_ 1783747100460187648
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
work_keys_str_mv AT baileysusanf effectsofsynonymousmutationsbeyondcodonbiastheevidenceforadaptivesynonymoussubstitutionsfrommicrobialevolutionexperiments
AT alonsomoralesluzangela effectsofsynonymousmutationsbeyondcodonbiastheevidenceforadaptivesynonymoussubstitutionsfrommicrobialevolutionexperiments
AT kassenrees effectsofsynonymousmutationsbeyondcodonbiastheevidenceforadaptivesynonymoussubstitutionsfrommicrobialevolutionexperiments