Pacing a small cage: mutation and RNA viruses

Abstract

RNA viruses have an extremely high mutation rate, and we argue that the most plausible explanation for this is a trade-off with replication speed. We suggest that research into further increasing this mutation rate artificially as an antiviral treatment requires a theoretical reevaluation, especially relating to the so-called error threshold. The main evolutionary consequence of a high mutation rate appears to have been to restrict RNA viruses to a small genome; they thus rapidly exploit a limited array of possibilities. Investigating this constraint to their evolution, and how it is occasionally overcome, promises to be fruitful. We explain the many terms used in investigating RNA viral evolution and highlight the specific experimental and comparative work that needs to be done.

Figure I

Possible fitness landscapes. Profile (a) is assumed by the basic quasispecies model, whereas empirical evidence suggests the landscape is closer to profile (b).

Figure 1

Genome lengths for RNA (a) and DNA (b) viruses showing the much greater range of the latter, extending beyond the size of the smallest known bacterial genome (Carsonella ruddii at 160 kb). Data taken from the NCBI genome webpage (http://www.ncbi.nlm.nih.gov).

Figure 2

Relationship between mean protein size and genome lengths, showing a significant positive relationship for proteins with replicase activity (closed circles) but not for nucleocapid proteins (open triangles). Each data point represents the mean value for a family of RNA viruses (taken from our web application/database at http://virus.zoo.ox.ac.uk/virus/index.html).