Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus

Mosquitoes of the genus Aedes are the main vectors of many viruses, e.g. dengue and Zika, which affect millions of people each year and for which there are limited treatment options. Understanding how Aedes mosquitoes tolerate high viral loads may lead to better disease control strategies. Elucidating endogenous viral elements (EVEs) within vector genomes may give exploitable biological insights. Previous studies have reported the presence of a large number of EVEs in Aedes genomes. Here we investigated if flavivirus EVEs are conserved across populations and different Aedes species by using ~ 500 whole genome sequence libraries from Aedes aegypti and Aedes albopictus, sourced from colonies and field mosquitoes across continents. We found that nearly all flavivirus EVEs in the Ae. aegypti reference genome originate from four separate putative viral integration events, and that they are highly conserved across geographically diverse samples. By contrast, flavivirus EVEs in the Ae. albopictus reference genome originate from up to nine distinct integration events and show low levels of conservation, even within samples from narrow geographical ranges. Our analysis suggests that flaviviruses integrated as long sequences and were subsequently fragmented and shuffled by transposable elements. Given that EVEs of Ae. aegypti and Ae. albopictus belong to different phylogenetic clades and have very differing levels of conservation, they may have different evolutionary origins and potentially different functional roles.