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MBE Advance Access published online on January 11, 2007
Molecular Biology and Evolution, 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 Article

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

Oliver G. Pybus1,*, Andrew Rambaut1, Robert Belshaw1, Robert P. Freckleton1, Alexei J. Drummond1,2 and Edward C. Holmes3,4

1 Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, U.K
2 Department of Computer Science, University of Auckland, Private Bag 92019, Auckland, New Zealand
3 Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, Mueller Laboratory, University Park, PA 16802. USA
4 Fogarty International Center, National Institutes of Health, Bethesda, MD 20892. USA

* To whom correspondence should be addressed. 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. Herein we develop a phylogenetic method, based on the distribution of non-synonymous 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.


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