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A beneficial synonymous substitution in EF-Tu is contingent on genetic background

Synonymous mutations are changes to DNA sequence that occur within translated genes but which do not affect the protein sequence. Although often referred to as silent mutations, evidence suggests that synonymous mutations can affect gene expression, mRNA stability, and even translation efficiency. A...

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Autores principales: McGrath, Kaitlyn M., Russell, Steven J., Fer, Evrim, Garmendia, Eva, Hosgel, Ali, Baltrus, David A., Kaçar, Betül
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602032/
https://www.ncbi.nlm.nih.gov/pubmed/37886545
http://dx.doi.org/10.1101/2023.09.06.555949
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author McGrath, Kaitlyn M.
Russell, Steven J.
Fer, Evrim
Garmendia, Eva
Hosgel, Ali
Baltrus, David A.
Kaçar, Betül
author_facet McGrath, Kaitlyn M.
Russell, Steven J.
Fer, Evrim
Garmendia, Eva
Hosgel, Ali
Baltrus, David A.
Kaçar, Betül
author_sort McGrath, Kaitlyn M.
collection PubMed
description Synonymous mutations are changes to DNA sequence that occur within translated genes but which do not affect the protein sequence. Although often referred to as silent mutations, evidence suggests that synonymous mutations can affect gene expression, mRNA stability, and even translation efficiency. A collection of both experimental and bioinformatic data has shown that synonymous mutations can impact cell phenotype, yet less is known about the molecular mechanisms and potential of beneficial or adaptive effects of such changes within evolved populations. Here, we report a beneficial synonymous mutation acquired via experimental evolution in an essential gene variant encoding the translation Elongation Factor protein EF-Tu. We demonstrate that this particular synonymous mutation increases EF-Tu mRNA and protein levels, as well as the polysome abundance on global transcripts. Although presence of the synonymous mutation is clearly causative of such changes, we also demonstrate that fitness benefits are highly contingent on other potentiating mutations present within the genetic background in which the mutation arose. Our results underscore the importance of beneficial synonymous mutations, especially those that affect levels of proteins that are key for cellular processes.
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spelling pubmed-106020322023-10-27 A beneficial synonymous substitution in EF-Tu is contingent on genetic background McGrath, Kaitlyn M. Russell, Steven J. Fer, Evrim Garmendia, Eva Hosgel, Ali Baltrus, David A. Kaçar, Betül bioRxiv Article Synonymous mutations are changes to DNA sequence that occur within translated genes but which do not affect the protein sequence. Although often referred to as silent mutations, evidence suggests that synonymous mutations can affect gene expression, mRNA stability, and even translation efficiency. A collection of both experimental and bioinformatic data has shown that synonymous mutations can impact cell phenotype, yet less is known about the molecular mechanisms and potential of beneficial or adaptive effects of such changes within evolved populations. Here, we report a beneficial synonymous mutation acquired via experimental evolution in an essential gene variant encoding the translation Elongation Factor protein EF-Tu. We demonstrate that this particular synonymous mutation increases EF-Tu mRNA and protein levels, as well as the polysome abundance on global transcripts. Although presence of the synonymous mutation is clearly causative of such changes, we also demonstrate that fitness benefits are highly contingent on other potentiating mutations present within the genetic background in which the mutation arose. Our results underscore the importance of beneficial synonymous mutations, especially those that affect levels of proteins that are key for cellular processes. Cold Spring Harbor Laboratory 2023-09-08 /pmc/articles/PMC10602032/ /pubmed/37886545 http://dx.doi.org/10.1101/2023.09.06.555949 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
McGrath, Kaitlyn M.
Russell, Steven J.
Fer, Evrim
Garmendia, Eva
Hosgel, Ali
Baltrus, David A.
Kaçar, Betül
A beneficial synonymous substitution in EF-Tu is contingent on genetic background
title A beneficial synonymous substitution in EF-Tu is contingent on genetic background
title_full A beneficial synonymous substitution in EF-Tu is contingent on genetic background
title_fullStr A beneficial synonymous substitution in EF-Tu is contingent on genetic background
title_full_unstemmed A beneficial synonymous substitution in EF-Tu is contingent on genetic background
title_short A beneficial synonymous substitution in EF-Tu is contingent on genetic background
title_sort beneficial synonymous substitution in ef-tu is contingent on genetic background
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602032/
https://www.ncbi.nlm.nih.gov/pubmed/37886545
http://dx.doi.org/10.1101/2023.09.06.555949
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