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Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence

When new genes evolve through modification of existing genes, there are often tradeoffs between the new and original functions, making gene duplication and amplification necessary to buffer deleterious effects on the original function. We have used experimental evolution of a bacterial strain lackin...

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Autores principales: Abdalaal, Hind, Pundir, Shreya, Ge, Xueliang, Sanyal, Suparna, Näsvall, Joakim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530605/
https://www.ncbi.nlm.nih.gov/pubmed/32437534
http://dx.doi.org/10.1093/molbev/msaa129
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author Abdalaal, Hind
Pundir, Shreya
Ge, Xueliang
Sanyal, Suparna
Näsvall, Joakim
author_facet Abdalaal, Hind
Pundir, Shreya
Ge, Xueliang
Sanyal, Suparna
Näsvall, Joakim
author_sort Abdalaal, Hind
collection PubMed
description When new genes evolve through modification of existing genes, there are often tradeoffs between the new and original functions, making gene duplication and amplification necessary to buffer deleterious effects on the original function. We have used experimental evolution of a bacterial strain lacking peptide release factor 1 (RF1) in order to study how peptide release factor 2 (RF2) evolves to compensate the loss of RF1. As expected, amplification of the RF2-encoding gene prfB to high copy number was a rapid initial response, followed by the appearance of mutations in RF2 and other components of the translation machinery. Characterization of the evolved RF2 variants by their effects on bacterial growth rate, reporter gene expression, and in vitro translation termination reveals a complex picture of reduced discrimination between the cognate and near-cognate stop codons and highlights a functional tradeoff that we term “collateral toxicity.” We suggest that this type of tradeoff may be a more serious obstacle in new gene evolution than the more commonly discussed evolutionary tradeoffs between “old” and “new” functions of a gene, as it cannot be overcome by gene copy number changes. Further, we suggest a model for how RF2 autoregulation responds to alterations in the demand not only for RF2 activity but also for RF1 activity.
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spelling pubmed-75306052020-10-07 Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence Abdalaal, Hind Pundir, Shreya Ge, Xueliang Sanyal, Suparna Näsvall, Joakim Mol Biol Evol Discoveries When new genes evolve through modification of existing genes, there are often tradeoffs between the new and original functions, making gene duplication and amplification necessary to buffer deleterious effects on the original function. We have used experimental evolution of a bacterial strain lacking peptide release factor 1 (RF1) in order to study how peptide release factor 2 (RF2) evolves to compensate the loss of RF1. As expected, amplification of the RF2-encoding gene prfB to high copy number was a rapid initial response, followed by the appearance of mutations in RF2 and other components of the translation machinery. Characterization of the evolved RF2 variants by their effects on bacterial growth rate, reporter gene expression, and in vitro translation termination reveals a complex picture of reduced discrimination between the cognate and near-cognate stop codons and highlights a functional tradeoff that we term “collateral toxicity.” We suggest that this type of tradeoff may be a more serious obstacle in new gene evolution than the more commonly discussed evolutionary tradeoffs between “old” and “new” functions of a gene, as it cannot be overcome by gene copy number changes. Further, we suggest a model for how RF2 autoregulation responds to alterations in the demand not only for RF2 activity but also for RF1 activity. Oxford University Press 2020-05-21 /pmc/articles/PMC7530605/ /pubmed/32437534 http://dx.doi.org/10.1093/molbev/msaa129 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. http://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/), 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 Discoveries
Abdalaal, Hind
Pundir, Shreya
Ge, Xueliang
Sanyal, Suparna
Näsvall, Joakim
Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence
title Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence
title_full Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence
title_fullStr Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence
title_full_unstemmed Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence
title_short Collateral Toxicity Limits the Evolution of Bacterial Release Factor 2 toward Total Omnipotence
title_sort collateral toxicity limits the evolution of bacterial release factor 2 toward total omnipotence
topic Discoveries
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530605/
https://www.ncbi.nlm.nih.gov/pubmed/32437534
http://dx.doi.org/10.1093/molbev/msaa129
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