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Mutation Bias Favors Protein Folding Stability in the Evolution of Small Populations

Mutation bias in prokaryotes varies from extreme adenine and thymine (AT) in obligatory endosymbiotic or parasitic bacteria to extreme guanine and cytosine (GC), for instance in actinobacteria. GC mutation bias deeply influences the folding stability of proteins, making proteins on the average less...

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Autores principales: Mendez, Raul, Fritsche, Miriam, Porto, Markus, Bastolla, Ugo
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865504/
https://www.ncbi.nlm.nih.gov/pubmed/20463869
http://dx.doi.org/10.1371/journal.pcbi.1000767
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author Mendez, Raul
Fritsche, Miriam
Porto, Markus
Bastolla, Ugo
author_facet Mendez, Raul
Fritsche, Miriam
Porto, Markus
Bastolla, Ugo
author_sort Mendez, Raul
collection PubMed
description Mutation bias in prokaryotes varies from extreme adenine and thymine (AT) in obligatory endosymbiotic or parasitic bacteria to extreme guanine and cytosine (GC), for instance in actinobacteria. GC mutation bias deeply influences the folding stability of proteins, making proteins on the average less hydrophobic and therefore less stable with respect to unfolding but also less susceptible to misfolding and aggregation. We study a model where proteins evolve subject to selection for folding stability under given mutation bias, population size, and neutrality. We find a non-neutral regime where, for any given population size, there is an optimal mutation bias that maximizes fitness. Interestingly, this optimal GC usage is small for small populations, large for intermediate populations and around 50% for large populations. This result is robust with respect to the definition of the fitness function and to the protein structures studied. Our model suggests that small populations evolving with small GC usage eventually accumulate a significant selective advantage over populations evolving without this bias. This provides a possible explanation to the observation that most species adopting obligatory intracellular lifestyles with a consequent reduction of effective population size shifted their mutation spectrum towards AT. The model also predicts that large GC usage is optimal for intermediate population size. To test these predictions we estimated the effective population sizes of bacterial species using the optimal codon usage coefficients computed by dos Reis et al. and the synonymous to non-synonymous substitution ratio computed by Daubin and Moran. We found that the population sizes estimated in these ways are significantly smaller for species with small and large GC usage compared to species with no bias, which supports our prediction.
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spelling pubmed-28655042010-05-12 Mutation Bias Favors Protein Folding Stability in the Evolution of Small Populations Mendez, Raul Fritsche, Miriam Porto, Markus Bastolla, Ugo PLoS Comput Biol Research Article Mutation bias in prokaryotes varies from extreme adenine and thymine (AT) in obligatory endosymbiotic or parasitic bacteria to extreme guanine and cytosine (GC), for instance in actinobacteria. GC mutation bias deeply influences the folding stability of proteins, making proteins on the average less hydrophobic and therefore less stable with respect to unfolding but also less susceptible to misfolding and aggregation. We study a model where proteins evolve subject to selection for folding stability under given mutation bias, population size, and neutrality. We find a non-neutral regime where, for any given population size, there is an optimal mutation bias that maximizes fitness. Interestingly, this optimal GC usage is small for small populations, large for intermediate populations and around 50% for large populations. This result is robust with respect to the definition of the fitness function and to the protein structures studied. Our model suggests that small populations evolving with small GC usage eventually accumulate a significant selective advantage over populations evolving without this bias. This provides a possible explanation to the observation that most species adopting obligatory intracellular lifestyles with a consequent reduction of effective population size shifted their mutation spectrum towards AT. The model also predicts that large GC usage is optimal for intermediate population size. To test these predictions we estimated the effective population sizes of bacterial species using the optimal codon usage coefficients computed by dos Reis et al. and the synonymous to non-synonymous substitution ratio computed by Daubin and Moran. We found that the population sizes estimated in these ways are significantly smaller for species with small and large GC usage compared to species with no bias, which supports our prediction. Public Library of Science 2010-05-06 /pmc/articles/PMC2865504/ /pubmed/20463869 http://dx.doi.org/10.1371/journal.pcbi.1000767 Text en Mendez et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mendez, Raul
Fritsche, Miriam
Porto, Markus
Bastolla, Ugo
Mutation Bias Favors Protein Folding Stability in the Evolution of Small Populations
title Mutation Bias Favors Protein Folding Stability in the Evolution of Small Populations
title_full Mutation Bias Favors Protein Folding Stability in the Evolution of Small Populations
title_fullStr Mutation Bias Favors Protein Folding Stability in the Evolution of Small Populations
title_full_unstemmed Mutation Bias Favors Protein Folding Stability in the Evolution of Small Populations
title_short Mutation Bias Favors Protein Folding Stability in the Evolution of Small Populations
title_sort mutation bias favors protein folding stability in the evolution of small populations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865504/
https://www.ncbi.nlm.nih.gov/pubmed/20463869
http://dx.doi.org/10.1371/journal.pcbi.1000767
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