Weitz Group @ Georgia Tech Theoretical Ecology and Quantitative Biology

Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations, Sardanyes et al. (2014), DOI: 10.1038/srep04625

Posted by abhiram
Wed, 09/24/2014

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.