Endemic/epidemic dengue viruses (DEN) that are transmitted among humans by
the mosquito vectors Aedes aegypti and Aedes albopictus are hypothesized to
have evolved from sylvatic DEN strains that are transmitted among nonhuman
primates in West Africa and Malaysia by other Aedes mosquitoes. We tested
this hypothesis with phylogenetic studies using envelope protein gene seque
nces of both endemic/epidemic and sylvatic strains. The basal position of s
ylvatic lineages of DEN-1, -2, and -4 suggested that the endemic/epidemic l
ineages of these three DEN serotypes evolved independently from sylvatic pr
ogenitors. Time estimates for evolution of the endemic/epidemic forms range
d from 100 to 1,500 years ago, and the evolution of endemic/epidemic forms
represents relatively recent events in the history of DEN evolution. Analys
is of envelope protein amino acid changes predicted to have accompanied end
emic/epidemic emergence suggested a role for domain III in adaptation to ne
w mosquito and/or human hosts.