Why are RNA virus mutation rates so damn high?

Siobain Duffy

doi:10.1371/journal.pbio.3000003

Abstract

The high mutation rate of RNA viruses is credited with their evolvability and virulence. This Primer, however, discusses recent evidence that this is, in part, a byproduct of selection for faster genomic replication.

Highlights

RNA viruses have high mutation rates—up to a million times higher than their hosts—and these high rates are correlated with enhanced virulence and evolvability, traits considered beneficial for viruses
RNA viruses are perhaps the most intriguing biological entities in which to study mutation rates. They encode their replication machinery, and their mutation rates can be optimized for their fitness. Their inherently high mutation rates yield offspring that differ by 1–2 mutations each from their parent [9], producing a mutant cloud of descendants that complicates our conception of a genotype’s fitness
One of the best-studied systems for RNA virus mutation is poliovirus, in which a frequently used lower mutation rate mutant (G64S in the 3D RNA-dependent RNA polymerase, 3D:G64S) was characterized, simultaneously, by virologists working at two locations in the San Francisco Bay Area [17, 18]

Summary

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RNA viruses have high mutation rates—up to a million times higher than their hosts—and these high rates are correlated with enhanced virulence and evolvability, traits considered beneficial for viruses. Their mutation rates are almost disastrously high, and a small increase in mutation rate can cause RNA viruses to go locally extinct. The fabled mutation rates of RNA viruses appear to be partially a consequence of selection on another trait, not because such a high mutation rate is optimal in and of itself. Many mutations cause organisms to leave fewer descendants over time, so the action of natural selection on these mutations is to purge them from the population.

Mutation rates are evolvable and can respond to selection

Poliovirus mutation rate and fidelity