From Molecular Genetics to Phylodynamics: Evolutionary Relevance of Mutation Rates Across Viruses

Abstract

Although evolution is a multifactorial process, theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear. To what extent these two biochemical and population-scale processes are related in nature, however, is largely unknown. Viruses are an ideal system for addressing this question because their evolution is fast enough to be observed in real time, and experimentally-determined mutation rates are abundant. This article provides statistically supported evidence that the mutation rate determines molecular evolution across all types of viruses. Properties of the viral genome such as its size and chemical composition are identified as major determinants of these rates. Furthermore, a quantitative analysis reveals that, as expected, evolution rates increase linearly with mutation rates for slowly mutating viruses. However, this relationship plateaus for fast mutating viruses. A model is proposed in which deleterious mutations impose an evolutionary speed limit and set an extinction threshold in nature. The model is consistent with data from replication kinetics, selection strength and chemical mutagenesis studies.

Author Summary

Viruses are an excellent system for addressing the evolutionary implications of mutation because their mutation rates vary by orders of magnitude, and their evolution takes place within the time frame of human observation. Theory posits a direct relationship between these two processes, but this has rarely been tested empirically. This work shows that evolution rates in nature correlate with experimentally-determined mutation rates for the major viral groups, and identifies key genome properties determining these rates. Current theory allows us to predict evolution rates accurately for slowly-mutating viruses but fails for the fastest mutating viruses. To solve this limitation, a model in which deleterious mutations play a key evolutionary role is proposed.