Comparative genomics of Japanese encephalitis virus shows low rates of recombination and a suite of sites under episodic diversifying selection

Japanese encephalitis virus (JEV) is the dominant cause of viral encephalitis in the Asian region with 100,000 cases and 25,000 deaths reported annually. The genome is comprised of a single polyprotein that encodes three structural and seven non-structural proteins. We collated a dataset of 347 complete genomes from a number of public databases, and analysed the data for recombination, evolutionary selection and phylogenetic structure. There are low rates of recombination in JEV, subsequently recombination is not a major evolutionary force shaping JEV. We found a strong overall signal of purifying selection in the genome, which is the main force affecting the evolutionary dynamics in JEV. There are also a small number of genomic sites under episodic diversifying selection, especially in the envelope protein and non-structural proteins 3 and 5. Overall, these results support previous analyses of JEV evolutionary genomics and provide additional insight into the evolutionary processes shaping the distribution and adaptation of this important pathogenic arbovirus. Author SummaryThis comparative study of Japanese Encephalitis Virus is the largest genomic analysis of the virus to date. We undertake a suite of analyses to investigate phylogenetic relationships, rates of recombination and patterns of genomic selection. We show that recombination is not a significant driver of evolution in JEV, demonstrate support for previous phylogenetic reconstructions of the virus, and find a number of sites across the genome under episodic diversifying selection. These adaptive hotspots of evolution serve as key genomic points for the adaptive evolution of this important vector borne pathogen.