Rapid evolution of mosquito anti-viral ncRNA pathway components

Vector-host non-coding RNA (ncRNA) interactions are important for the maintenance of arthropod-borne virus (arbovirus) infection cycles in nature. A major anti-viral pathway in mosquitoes is the RNA interference (RNAi) pathway. Using high throughput sequencing (HTS) data, population genetics analysis was performed on major RNAi components from natural populations of the dengue and zika virus vector, Aedes aegypti. Pairwise comparisons of four geographically separated wild-caught collections (Senegal, Thailand, and Mexico) were analyzed for this study. Mutation rate ratios of siRNA/miRNA orthologs indicated rapid evolution of anti-viral siRNA pathway components, as had been reported previously. Polymorphisms were present in key amino acid residues of RNAi pathway components, which could contribute to variability in arbovirus infection rates, and thereby influence transmission cycles. Haplotype analysis of Argonaute-2 (Ago2), the RNAi slicer enzyme, revealed a hypervariable region in the predicted N-terminus that varied widely among the populations, as well as polymorphisms in the PAZ and PIWI domains. Dicer-2 showed selected coding changes near the DEAD/DEAH helicase, dimerization, and RNase III domains, which also varied among the collections. Senegal (PK10) showed the highest number of coding changes in Ago2 and Dicer-2. Rapid evolution of RNAi components may influence emergence of arbovirus genotypes and contribute to the inter-kingdom arms race of arbovirus pathogens and their hosts.