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Journal of Virology, October 2003, p. 11296-11298, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11296-11298.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Patterns of Intra- and Interhost Nonsynonymous Variation Reveal Strong Purifying Selection in Dengue Virus

Edward C. Holmes*

Department of Zoology, University of Oxford, Oxford, United Kingdom

Received 25 April 2003/ Accepted 22 July 2003

Considerable uncertainty surrounds the evolutionary rates of and selection pressures acting on arthropod-borne RNA viruses (arboviruses). In particular, it is unclear why arboviruses such as dengue virus show substantial genetic variation within individual humans and mosquitoes yet low long-term rates of amino acid substitution. To address this question, I compared patterns of nonsynonymous variation in populations of dengue virus sampled at different levels of evolutionary divergence. Although nonsynonymous variation was abundant in viral populations within individual humans, there was a marked reduction in the frequency of nonsynonymous mutations in interhost comparisons. Moreover, intrahost genetic variation corresponded to a random pattern of mutation, and most of the sites that exhibited nonsynonymous variation within hosts were invariant at deeper phylogenetic levels. This loss of long-term nonsynonymous variation is the signature of extensive purifying selection such that more than 90% of all nonsynonymous mutations are deleterious. Consequently, although arboviruses are able to successfully adapt to diverse cell types, they are characterized by a high rate of deleterious mutation.

* Mailing address: Department of Zoology, University of Oxford, South Parks Rd., Oxford OXI 3PS, United Kingdom. Phone: 44 1865 271282. Fax: 44 1865 310447. E-mail: Edward.Holmes{at}zoo.ox.ac.uk.

Journal of Virology, October 2003, p. 11296-11298, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11296-11298.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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