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

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

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dc.contributor.author Sardanyes Cayuela, Jose es_ES
dc.contributor.author Simó, Carles es_ES
dc.contributor.author Martínez, Regina es_ES
dc.contributor.author Solé, Ricard V. es_ES
dc.contributor.author Elena Fito, Santiago Fco es_ES
dc.date.accessioned 2017-05-18T11:43:01Z
dc.date.available 2017-05-18T11:43:01Z
dc.date.issued 2014-04-09
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10251/81389
dc.description.abstract [EN] 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. es_ES
dc.description.sponsorship We thank the members of the Complex Systems Lab as well as Phillip Gerrish, Susanna C. Manrubia, and Ernest Fontich for their helpful comments. The authors acknowledge the computing facilities of the Dynamical Systems Group (Universitat de Barcelona). This work was partially funded by the Botin Foundation (JS, RVS), by the Spanish Secretaria de Estado de Investigacion, Desarrollo e Innovacion 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). en_EN
dc.language Inglés es_ES
dc.publisher Nature Publishing Group es_ES
dc.relation.ispartof Scientific Reports es_ES
dc.rights Reconocimiento - No comercial - Sin obra derivada (by-nc-nd) es_ES
dc.subject Single-nucleotide substitutions es_ES
dc.subject Immunodeficiency-virus type-1 es_ES
dc.subject Vesicular stomatitis-virus es_ES
dc.subject Tobacco-ETCH-virus es_ES
dc.subject Error threshold es_ES
dc.subject RNA virus es_ES
dc.subject Deleterious mutations es_ES
dc.subject Muller ratchet es_ES
dc.subject Human cancers es_ES
dc.subject Evolution es_ES
dc.title Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1038/srep04625 es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Instituto Universitario Mixto de Biología Molecular y Celular de Plantas - Institut Universitari Mixt de Biologia Molecular i Cel·lular de Plantes es_ES
dc.description.bibliographicCitation Sardanyes Cayuela, J.; Simó, C.; Martínez, R.; Solé, RV.; Elena Fito, SF. (2014). Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations. Scientific Reports. (4):1-9. doi:10.1038/srep04625 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion http://doi.org/10.1038/srep04625 es_ES
dc.description.upvformatpinicio 1 es_ES
dc.description.upvformatpfin 9 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.issue 4 es_ES
dc.relation.senia 266232 es_ES
dc.identifier.pmid 24713667 en_EN
dc.identifier.pmcid PMC3980229
dc.contributor.funder Fundación Botín es_ES
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