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, neutral, de...

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Bibliographic Details
Authors: Sardanyés, Josep|||0000-0001-7225-5158; Simó, Carles; Martínez Barchino, Regina|||0000-0002-1328-6744; Solé, Ricard|||0000-0001-6974-1008; Elena, Santiago F.|||0000-0001-8249-5593
Format: Article
Publication date:2014
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:206005
Online Access:https://ddd.uab.cat/record/206005
https://dx.doi.org/urn:doi:10.1038/srep04625
Access Level:Open access
Description
Summary: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.