Structure and age of genetic diversity of dengue virus type 2 in Thailand.

Dengue virus type 2 (DENV-2) is a common viral infection and an important health concern in South-East Asia. To determine the molecular evolution of DENV-2 in Thailand, 105 isolates of the E (envelope) gene and 10 complete genomes sampled over a 27 year period were sequenced. Phylogenetic analysis of these data revealed that three genotypes of DENV-2 have circulated in Thailand, although, since 1991, only viruses assigned to Asian genotype I have been sampled from the population. A broader analysis of 35 complete genomes of DENV-2 revealed that most amino acids are subject to strong selective constraints, indicative of widespread purifying selection against deleterious mutations. This was further supported by an analysis of genome-wide substitution rates, which indicated that DENV-2 fixes approximately 10 mutations per genome per year, far lower than expected from its mutational dynamics. Finally, estimates of the age of DENV-2 were remarkably consistent among genes, indicating that the current genetic diversity in this virus probably arose within the last 120 years, concordant with the first determination of the aetiology of dengue disease.