Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations

The distribution of mutational fitness effects (DMFE) is crucial to the evolutionary fate of quasispecies. In this article we analyze the effect of the DMFE on the dynamics of a large quasispecies by means of a phenotypic version of the classic Eigen's model that incorporates beneficial, ne...

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Authors: Solé Vicente, Ricard, 1962-, Sardanyés i Cayuela, Josep, Simó, Carles, Martínez, Regina, Elena, Santiago F.
Format: article
Status:Published version
Publication Date:2014
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/24545
Online Access:http://hdl.handle.net/10230/24545
http://dx.doi.org/10.1038/srep04625
Access Level:Open access
Keyword:Genètica
Evolució (Biologia)
Evolutionary theory
Virology
Applied mathematics
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spelling Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populationsSolé Vicente, Ricard, 1962-Sardanyés i Cayuela, JosepSimó, CarlesMartínez, ReginaElena, Santiago F.GenèticaEvolució (Biologia)Evolutionary theoryVirologyApplied mathematicsThe distribution of mutational fitness effects (DMFE) is crucial to the evolutionary fate of quasispecies. In this article we analyze the effect of the DMFE on the dynamics of a large quasispecies by means of a phenotypic version of the classic Eigen's model that incorporates beneficial, neutral, deleterious, and lethal mutations. By parameterizing the model with available experimental data on the DMFE of Vesicular stomatitis virus (VSV) and Tobacco etch virus (TEV), we found that increasing mutation does not totally push the entire viral quasispecies towards deleterious or lethal regions of the phenotypic sequence space. The probability of finding regions in the parameter space of the general model that results in a quasispecies only composed by lethal phenotypes is extremely small at equilibrium and in transient times. The implications of our findings can be extended to other scenarios, such as lethal mutagenesis or genomically unstable cancer, where increased mutagenesis has been suggested as a potential therapy.This work was partially funded by the Botín Foundation (JS, RVS), by the Spanish Secretaria de Estado de Investigación, Desarrollo e Innovación grants MTM2010-16425 (CS, RM) and BFU2012-30805 (SFE), by grant 2009-SGR-67 from the Catalan government (CS, RM), by grant NSF PHY05-51164 (JS, SFE), and by the Santa Fe Institute (RVS, SFE).Nature Publishing Group201520152014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/24545http://dx.doi.org/10.1038/srep04625reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésScientific Reports. 2014;4:4625info:eu-repo/grantAgreement/ES/3PN/MTM2010-16425info:eu-repo/grantAgreement/ES/3PN/BFU2012-30805© Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images in this article are included in the article's Creative Commons license, unless indicated otherwise in the image credit; if the image is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the imagehttp://creativecommons.org/licenses/by-nc-nd/3.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/245452026-05-29T05:05:01Z
dc.title.none.fl_str_mv Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations
title Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations
spellingShingle Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations
Solé Vicente, Ricard, 1962-
Genètica
Evolució (Biologia)
Evolutionary theory
Virology
Applied mathematics
title_short Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations
title_full Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations
title_fullStr Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations
title_full_unstemmed Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations
title_sort Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations
dc.creator.none.fl_str_mv Solé Vicente, Ricard, 1962-
Sardanyés i Cayuela, Josep
Simó, Carles
Martínez, Regina
Elena, Santiago F.
author Solé Vicente, Ricard, 1962-
author_facet Solé Vicente, Ricard, 1962-
Sardanyés i Cayuela, Josep
Simó, Carles
Martínez, Regina
Elena, Santiago F.
author_role author
author2 Sardanyés i Cayuela, Josep
Simó, Carles
Martínez, Regina
Elena, Santiago F.
author2_role author
author
author
author
dc.subject.none.fl_str_mv Genètica
Evolució (Biologia)
Evolutionary theory
Virology
Applied mathematics
topic Genètica
Evolució (Biologia)
Evolutionary theory
Virology
Applied mathematics
description The distribution of mutational fitness effects (DMFE) is crucial to the evolutionary fate of quasispecies. In this article we analyze the effect of the DMFE on the dynamics of a large quasispecies by means of a phenotypic version of the classic Eigen's model that incorporates beneficial, neutral, deleterious, and lethal mutations. By parameterizing the model with available experimental data on the DMFE of Vesicular stomatitis virus (VSV) and Tobacco etch virus (TEV), we found that increasing mutation does not totally push the entire viral quasispecies towards deleterious or lethal regions of the phenotypic sequence space. The probability of finding regions in the parameter space of the general model that results in a quasispecies only composed by lethal phenotypes is extremely small at equilibrium and in transient times. The implications of our findings can be extended to other scenarios, such as lethal mutagenesis or genomically unstable cancer, where increased mutagenesis has been suggested as a potential therapy.
publishDate 2014
dc.date.none.fl_str_mv 2014
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/24545
http://dx.doi.org/10.1038/srep04625
url http://hdl.handle.net/10230/24545
http://dx.doi.org/10.1038/srep04625
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Scientific Reports. 2014;4:4625
info:eu-repo/grantAgreement/ES/3PN/MTM2010-16425
info:eu-repo/grantAgreement/ES/3PN/BFU2012-30805
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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