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MBE Advance Access originally published online on January 11, 2007
Molecular Biology and Evolution 2007 24(3):845-852; doi:10.1093/molbev/msm001
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© The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Articles

Phylogenetic Evidence for Deleterious Mutation Load in RNA Viruses and Its Contribution to Viral Evolution

Oliver G. Pybus*, Andrew Rambaut*, Robert Belshaw*, Robert P. Freckleton*, Alexei J. Drummond*,{dagger} and Edward C. Holmes{ddagger},§

* Department of Zoology, University of Oxford, Oxford, United Kingdom
{dagger} Department of Computer Science, University of Auckland, Auckland, New Zealand
{ddagger} Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University
§ Fogarty International Center, National Institutes of Health, Bethesda, Maryland

E-mail: oliver.pybus{at}zoo.ox.ac.uk.

Accepted for publication December 22, 2006.

Populations of RNA viruses are often characterized by abundant genetic variation. However, the relative fitness of these mutations is largely unknown, although this information is central to our understanding of viral emergence, immune evasion, and drug resistance. Here we develop a phylogenetic method, based on the distribution of nonsynonymous and synonymous changes, to assess the relative fitness of polymorphisms in the structural genes of 143 RNA viruses. This reveals that a substantial proportion of the amino acid variation observed in natural populations of RNA viruses comprises transient deleterious mutations that are later purged by purifying selection, potentially limiting virus adaptability. We also demonstrate, for the first time, the existence of a relationship between amino acid variability and the phylogenetic distribution of polymorphisms. From this relationship, we propose an empirical threshold for the maximum viable deleterious mutation load in RNA viruses.

Key Words: virus • deleterious mutation • phylogeny

William Martin, Associate Editor


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