Dengue is a major health problem in India with all four serotypes represented. Recently there has been an increase in the occurrence of dengue-1 outbreaks. It is possible that there have been changes in the genetics of dengue virus-1 (DENV-1), either by fresh introductions or by evolution in situ. The studies on DENV-1 evolution so far have no Indian sequences included. To gain insight into the dynamics of DENV-1 in India, the envelope (E) gene of thirteen virus isolates representative of the period 1962-2005 were sequenced and analyzed together with the available sequences of 40 globally representative isolates. All the Indian DENV-1 isolates were found to belong to the American African (AMAF) genotype. With the addition of 13 Indian isolates, the AMAF genotype can now be called Cosmopolitan. The Indian isolates were distributed into four lineages, India I, II, III and the Africa lineage, now called Afro-India. Of these, India III was the oldest and extinct lineage; the Afro-India was a transient lineage while India I, imported from Singapore and India II, evolving in situ, were the circulating lineages. Despite the extinction and introduction of lineages, no specific codon site was observed to be under selection pressure. The rate of nucleotide substitution estimated for DENV-1 was 6.5 × 10(-4) substitutions/site/year, and the time to the most recent common ancestor (tMRCA) was estimated to be 78-180 years (1825-1925), similar to previous estimates. The tMRCA for the AMAF/Cosmopolitan genotype was 56-98 years (1907-1949), a period that covers World War I and II. The two imports from Africa (1953-1968) and Singapore (1964-1975) and an export to the Americas (1955-1965) prove that there have been changes in the lineage of the DENV-1 viruses circulating in India which has contributed to the global dynamics of DENV-1 evolution and perhaps to the changing epidemiology of dengue in India.
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