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, 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.
1] ICREA-Complex Systems Lab, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain [2] Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Passeig Maritim de la Barceloneta 37, 08003 Barcelona, Spain.
Josep
J
Sardanyés
Departament de Matemàtica Aplicada i Anàlisi (Universitat de Barcelona), Gran Via de les Corts Catalanes 585, 08007 Barcelona, Spain.
Carles
C
Simó
Departament de Matemàtiques, Edifici C. Facultat de Ciències (Universitat Autònoma de Barcelona) 08193, Bellaterra, Spain.
Regina
R
Martínez
1] ICREA-Complex Systems Lab, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain [2] Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Passeig Maritim de la Barceloneta 37, 08003 Barcelona, Spain [3] Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA.
Ricard V
RV
Solé
1] Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA [2] Instituto de Biología Molecular y Celular de Plantas (CSIC-UPV), Ingeniero Fausto Elio s/n, 46022 València, Spain.
Santiago F
SF
Elena
D005075:Biological Evolution; D019143:Evolution, Molecular; D005804:Genes, Lethal / Q000235:genetics*; D049810:Genetic Speciation; D016679:Genome, Viral / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation; D017800:Potyvirus / Q000235:genetics*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*