Comparative whole-genome analysis of Aedes aegypti field isolates from Southern India reveals global relatedness and localized genetic differentiation

In the past decade, whole-genome sequencing (WGS) and reduced-representation genome sequencing of wild populations of the invasive mosquito species Aedes aegypti have identified genetic markers of vectorial capacity for arboviruses, such as DENV, host seeking behavior, and insecticide resistance. However, neither technique has been applied to Indian Ae. aegypti field isolates, despite India bearing a high annual arboviral burden. To address this, we sequenced the whole genomes of eight Ae. aegypti mosquitoes sampled from dengue-endemic areas of Southern India and systematically investigated their genetic variability relative to the Ae. aegypti reference genome and global isolates using principal component analysis (PCA), ADMIXTURE, phylogenomics and other population statistical tests. While a preliminary analysis identified known markers of insecticide resistance in four Ae. aegypti genes, including the voltage-gated sodium channel (VGSC), genome-wide population statistical analyses suggested that genes encoding ion channels, transmembrane receptors and signaling molecules may be under selection in Southern India. Next, to obtain a global view of Ae. aegypti population structure and evolutionary relatedness, the South-Indian genomes were compared to publicly available genomes of Ae. aegypti field isolates from different parts of the world. Based on PCA and ADMIXTURE, we observed that African Ae. aegypti samples clustered as a single group while the American, Samoan and Asian samples—inclusive of the ones from Southern India—formed a second group, but with distinct geographical sub-grouping and showed evidence of new admixing ancestries. Furthermore, phylogenomic analysis suggested a single out-of-Africa exit of Ae. aegypti with a subset of the Southern Indian isolates having diverged recently from other Asian populations. Overall, our observations indicate ongoing genomic diversification of Ae. aegypti within Southern India, a factor that needs to be considered while designing vector control strategies such as insecticide-based control and those involving genetic modifications, such as gene drives.