Restriction to gene flow is associated with changes in the molecular basis of pyrethroid resistance in the malaria vector <i>Anopheles funestus</i>

Significance Vector control is the cornerstone of malaria prevention. Wide-scale distribution of treated bed nets and indoor residual spraying throughout Africa has led to a major decrease in mortality, but insecticide resistance threatens this ongoing success. Here we show that across a highly endemic country, one of the main malaria vectors, Anopheles funestus , is resistant to several insecticide classes, including the insecticides used for bed nets. This study shows that multiple CYP450 s , genes linked to xenobiotic metabolism, are responsible for insecticide resistance, but their impact varies significantly depending on geography. Genetic diversity analysis revealed that this genomic variation is associated with barriers to gene flow between southern African populations of An. funestus . This work should help improve resistance management and vector control strategies throughout southern Africa.