MBE Advance Access published online on June 27, 2003
Molecular Biology and Evolution, doi:10.1093/molbev/msg182
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
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1 Department of Biology, University of Puerto Rico - Rio Piedras, San Juan, Puerto Rico
* To whom correspondence should be addressed. E-mail: sbennett{at}rrpac.upr.clu.edu.
In the last four decades the incidence of dengue fever has increased 30-fold worldwide and over half the world's population is now threatened with infection from one or more of four co-circulating viral serotypes (DEN-1-DEN-4). To determine the role of viral molecular evolution in emergent disease dynamics, we sequenced 40% of the genome of 82 DEN-4 isolates collected from Puerto Rico (PR) over a 20-year period since the onset of endemic dengue on the island. Isolates were derived from years with varying levels of DEN-4 prevalence. Over our sampling period there were marked evolutionary shifts in DEN-4 viral populations circulating in PR; viral lineages were temporally clustered and the most common genotype at a particular sampling time often arose from a previously rare lineage. Expressed changes in structural genes did not appear to drive this lineage turnover, even though these regions include primary determinants of viral antigenic properties. Instead, recent dengue evolution can be attributed in part to positive selection on the nonstructural gene 2A (NS2A), whose functions may include replication efficiency and antigenicity. During the latest and most severe DEN-4 epidemic in PR, in 1998, viruses were distinguished by three amino acid changes in NS2A that were fixed far faster than expected by drift alone. Our study therefore demonstrates viral genetic turnover within a focal population and the potential importance of adaptive evolution in viral epidemic expansion. Key Words:
dengue virus, positive selection, epidemiology, phylogeny, maximum likelihood
© 2003 Society for Molecular Biology and Evolution
Original Articles
Selection-Driven Evolution of Emergent Dengue Virus
2 Department of Zoology, University of Oxford, Oxford, England
3 Department of Microbiology and Medical Zoology, University of Puerto Rico - Ciencias Medicas, San Juan, Puerto Rico; Centers for Disease Control and Prevention, San Juan Branch, San Juan, Puerto Rico
4 Centers for Disease Control and Prevention, San Juan Branch, San Juan, Puerto Rico
5 Centers for Disease Control and Prevention, Fort Collins, Colorado
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