The cost of replication fidelity in an RNA virus

Abstract

It is often argued that high mutation rates are advantageous for RNA viruses, because they confer elevated rates of adaptation. However, there is no direct evidence showing a positive correlation between mutation and adaptation rates among RNA viruses. Moreover, theoretical work does not argue in favor of this prediction. We used a series of vesicular stomatitis virus clones harboring single amino acid substitutions in the RNA polymerase to demonstrate that changes inducing enhanced fidelity paid a fitness cost, but that there was no positive correlation between mutation an adaptation rates. We demonstrate that the observed mutation rate in vesicular stomatitis virus can be explained by a trade-off between replication rate and replication fidelity.

Fig. 1.

Expected relationships between fitness and mutation rate. Without a direct effect of the mutation rate modifier allele on fitness, the mean fitness is expected to exponentially decrease as a function of mutation rate because of increasing genetic load (dashed lines). By contrast, if there is a cost of fidelity, fitness can rise as the mutation rate increases. The solid line has only qualitative purposes.

Fig. 2.

Positive correlation between fitness and mutation rate, both relative to the wild type. Mean values, standard error bars, and the least-squares regression are shown.

Fig. 3.

Negative correlation between adaptation and ancestral mutation rates relative to the wild type. Mean values, standard error bars, and the least-squares regression are shown.