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MBE Advance Access published online on April 15, 2008
Molecular Biology and Evolution, doi:10.1093/molbev/msn093
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© The Author 2008. 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

High Rates of Molecular Evolution in Hantaviruses.

Cadhla Ramsden1, Fernando L. Melo2, Luiz. M. Figueiredo3, Edward C. Holmes1,4, Paolo M.A. Zanotto2 and the VGDN Consortium

1 Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA
2 LEMB, Institute of Biomedical Science, University of São Paulo, São Paulo, SP, Brazil
3 School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil
4 Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA

Corresponding Author: Paolo M.A. Zanotto, Mailing Address: 1374 Ave. Lineu Prestes, São Paulo, São Paulo, Brazil 05508-000, Telephone: 55 11 30917290, Fax: 55 11 30917290. Email: pzanotto{at}usp.br

Received for publication February 8, 2008. Revision received March 19, 2008. Accepted for publication April 10, 2008.

Hantaviruses are rodent-borne Bunyaviruses that infect the Arvicolinae, Murinae and Sigmodontinae subfamilies of Muridae. The rate of molecular evolution in the hantaviruses has been previously estimated at approximately 10-7 nucleotide substitutions per site, per year (subs/site/year), based on the assumption of co-divergence and hence shared divergence times with their rodent hosts. If substantiated, this would make the hantaviruses among the slowest evolving of all RNA viruses. However, as hantaviruses replicate with an RNA-dependent RNA polymerase, with error rates in the region of one mutation per genome replication, this low rate of nucleotide substitution is anomalous. Here, we use a Bayesian coalescent approach to estimate the rate of nucleotide substitution from serially sampled gene sequence data for hantaviruses known to infect each of the three rodent subfamilies: Araraquara virus (Sigmodontinae), Dobrava virus (Murinae), Puumala virus (Arvicolinae) and Tula virus (Arvicolinae). Our results reveal that hantaviruses exhibit short-term substitution rates of 10-2 to 10-4 subs/site/year, and so are within the range exhibited by other RNA viruses. The disparity between this substitution rate and that estimated assuming rodent-hantavirus co-divergence suggest that the co-divergence hypothesis may need to be re-evaluated.

Key Words: hantavirus • nucleotide substitution • molecular evolution • substitution rates


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