CYP6P9-Driven Signatures of Selective Sweep of Metabolic Resistance to Pyrethroids in the Malaria Vector Reveal Contemporary Barriers to Gene Flow.

Pyrethroid resistance in major malaria vectors such as threatens malaria control efforts in Africa. Cytochrome P450-mediated metabolic resistance is best understood for genes in southern Africa in . However, we do not know if this resistance mechanism is spreading across Africa and how it relates to broader patterns of gene flow across the continent. Nucleotide diversity of the gene and the diversity pattern of five gene fragments spanning a region of 120 kb around the gene were surveyed in mosquitoes from southern, eastern and central Africa. These analyses revealed that a resistance-associated allele has swept through southern and eastern Africa and is now fixed in these regions. A similar diversity profile was observed when analysing genomic regions located 34 kb upstream to 86 kb downstream of the locus, concordant with a selective sweep throughout the rp1 locus. We identify reduced gene flow between southern/eastern Africa and central Africa, which we hypothesise is due to the Great Rift Valley. These potential barriers to gene flow are likely to prevent or slow the spread of -based resistance mechanism to other parts of Africa and would to be considered in future vector control interventions such as gene drive.