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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Detalhes bibliográficos
Autores: Solé Vicente, Ricard, 1962-, Sardanyés i Cayuela, Josep, Simó, Carles, Martínez, Regina, Elena, Santiago F.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/24545
Acesso em linha:http://hdl.handle.net/10230/24545
http://dx.doi.org/10.1038/srep04625
Access Level:acceso abierto
Palavra-chave:Genètica
Evolució (Biologia)
Evolutionary theory
Virology
Applied mathematics
Descrição
Resumo: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.