Cryptic population structure and insecticide resistance inAnopheles gambiaefrom the southern Democratic Republic of Congo

Abstract

ABSTRACTThe Democratic Republic of Congo (DRC) suffers from one of the highest malaria burdens worldwide, but information on itsAnophelesvector populations is relatively limited. Preventative malaria control in DRC is reliant on pyrethroid-treated nets, raising concerns over the potential impacts of insecticide resistance. We sampledAnopheles gambiaefrom three geographically distinct populations (Kimpese, Kapolowe and Mikalayi) in southern DRC, collecting from three sub-sites per population and characterising mosquito collections from each for resistance to pyrethroids using WHO tube bioassays. Resistance to each of three different pyrethroids was generally high inAn. gambiaewith <92% mortality in all tests, but varied between collections, with mosquitoes from Kimpese being the most resistant.Whole genome sequencing of 165An. gambiaerevealed evidence for genetic differentiation between Kimpese and Kapolowe / Mikalayi, but not between the latter two sample sites despite separation of approximately 800km. Surprisingly, there was evidence of population structure at a small spatial scale between collection subsites in Kimpese, despite separation of just tens of kilometres. Intra-population (H12) and inter-population (FST) genome scans identified multiple peaks corresponding to genes associated with insecticide resistance such as the voltage gated sodium channel (Vgsc)target site on chromosome 2L, aCyp6cytochrome P450 cluster on chromosome arm 2R, and theCyp9k1P450 gene on chromosome X. In addition, in the Kimpese subsites, the P450 redox partner geneCprshowed evidence for contemporary selection (H12) and population differentiation (FST) meriting further exploration as a potential resistance associated marker.