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Initial Mutations Direct Alternative Pathways of Protein Evolution
Whether evolution is erratic due to random historical details, or is repeatedly directed along similar paths by certain constraints, remains unclear. Epistasis (i.e. non-additive interaction between mutations that affect fitness) is a mechanism that can contribute to both scenarios. Epistasis can co...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048372/ https://www.ncbi.nlm.nih.gov/pubmed/21408208 http://dx.doi.org/10.1371/journal.pgen.1001321 |
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author | Salverda, Merijn L. M. Dellus, Eynat Gorter, Florien A. Debets, Alfons J. M. van der Oost, John Hoekstra, Rolf F. Tawfik, Dan S. de Visser, J. Arjan G. M. |
author_facet | Salverda, Merijn L. M. Dellus, Eynat Gorter, Florien A. Debets, Alfons J. M. van der Oost, John Hoekstra, Rolf F. Tawfik, Dan S. de Visser, J. Arjan G. M. |
author_sort | Salverda, Merijn L. M. |
collection | PubMed |
description | Whether evolution is erratic due to random historical details, or is repeatedly directed along similar paths by certain constraints, remains unclear. Epistasis (i.e. non-additive interaction between mutations that affect fitness) is a mechanism that can contribute to both scenarios. Epistasis can constrain the type and order of selected mutations, but it can also make adaptive trajectories contingent upon the first random substitution. This effect is particularly strong under sign epistasis, when the sign of the fitness effects of a mutation depends on its genetic background. In the current study, we examine how epistatic interactions between mutations determine alternative evolutionary pathways, using in vitro evolution of the antibiotic resistance enzyme TEM-1 β-lactamase. First, we describe the diversity of adaptive pathways among replicate lines during evolution for resistance to a novel antibiotic (cefotaxime). Consistent with the prediction of epistatic constraints, most lines increased resistance by acquiring three mutations in a fixed order. However, a few lines deviated from this pattern. Next, to test whether negative interactions between alternative initial substitutions drive this divergence, alleles containing initial substitutions from the deviating lines were evolved under identical conditions. Indeed, these alternative initial substitutions consistently led to lower adaptive peaks, involving more and other substitutions than those observed in the common pathway. We found that a combination of decreased enzymatic activity and lower folding cooperativity underlies negative sign epistasis in the clash between key mutations in the common and deviating lines (Gly238Ser and Arg164Ser, respectively). Our results demonstrate that epistasis contributes to contingency in protein evolution by amplifying the selective consequences of random mutations. |
format | Text |
id | pubmed-3048372 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30483722011-03-15 Initial Mutations Direct Alternative Pathways of Protein Evolution Salverda, Merijn L. M. Dellus, Eynat Gorter, Florien A. Debets, Alfons J. M. van der Oost, John Hoekstra, Rolf F. Tawfik, Dan S. de Visser, J. Arjan G. M. PLoS Genet Research Article Whether evolution is erratic due to random historical details, or is repeatedly directed along similar paths by certain constraints, remains unclear. Epistasis (i.e. non-additive interaction between mutations that affect fitness) is a mechanism that can contribute to both scenarios. Epistasis can constrain the type and order of selected mutations, but it can also make adaptive trajectories contingent upon the first random substitution. This effect is particularly strong under sign epistasis, when the sign of the fitness effects of a mutation depends on its genetic background. In the current study, we examine how epistatic interactions between mutations determine alternative evolutionary pathways, using in vitro evolution of the antibiotic resistance enzyme TEM-1 β-lactamase. First, we describe the diversity of adaptive pathways among replicate lines during evolution for resistance to a novel antibiotic (cefotaxime). Consistent with the prediction of epistatic constraints, most lines increased resistance by acquiring three mutations in a fixed order. However, a few lines deviated from this pattern. Next, to test whether negative interactions between alternative initial substitutions drive this divergence, alleles containing initial substitutions from the deviating lines were evolved under identical conditions. Indeed, these alternative initial substitutions consistently led to lower adaptive peaks, involving more and other substitutions than those observed in the common pathway. We found that a combination of decreased enzymatic activity and lower folding cooperativity underlies negative sign epistasis in the clash between key mutations in the common and deviating lines (Gly238Ser and Arg164Ser, respectively). Our results demonstrate that epistasis contributes to contingency in protein evolution by amplifying the selective consequences of random mutations. Public Library of Science 2011-03-03 /pmc/articles/PMC3048372/ /pubmed/21408208 http://dx.doi.org/10.1371/journal.pgen.1001321 Text en Salverda et al. 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 credited. |
spellingShingle | Research Article Salverda, Merijn L. M. Dellus, Eynat Gorter, Florien A. Debets, Alfons J. M. van der Oost, John Hoekstra, Rolf F. Tawfik, Dan S. de Visser, J. Arjan G. M. Initial Mutations Direct Alternative Pathways of Protein Evolution |
title | Initial Mutations Direct Alternative Pathways of Protein Evolution |
title_full | Initial Mutations Direct Alternative Pathways of Protein Evolution |
title_fullStr | Initial Mutations Direct Alternative Pathways of Protein Evolution |
title_full_unstemmed | Initial Mutations Direct Alternative Pathways of Protein Evolution |
title_short | Initial Mutations Direct Alternative Pathways of Protein Evolution |
title_sort | initial mutations direct alternative pathways of protein evolution |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048372/ https://www.ncbi.nlm.nih.gov/pubmed/21408208 http://dx.doi.org/10.1371/journal.pgen.1001321 |
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