Genomic Footprints of Selective Sweeps from Metabolic Resistance to Pyrethroids in African Malaria Vectors Are Driven by Scale up of Insecticide-Based Vector Control.
Insecticide resistance in mosquito populations threatens recent successes in malaria prevention. Elucidating patterns of genetic structure in malaria vectors to predict the speed and direction of the spread of resistance is essential to get ahead of the 'resistance curve' and to avert a public health catastrophe. Here, applying a combination of microsatellite analysis, whole genome sequencing and targeted sequencing of a resistance locus, we elucidated the continent-wide population structure of a major African malaria vector, Anopheles funestus. We identified a major selective sweep in a genomic region controlling cytochrome P450-based metabolic resistance conferring high resistance to pyrethroids. This selective sweep occurred since 2002, likely as a direct consequence of scaled up vector control as revealed by whole genome and fine-scale sequencing of pre- and post-intervention populations. Fine-scaled analysis of the pyrethroid resistance locus revealed that a resistance-associated allele of the cytochrome P450 monooxygenase CYP6P9a has swept through southern Africa to near fixation, in contrast to high polymorphism levels before interventions, conferring high levels of pyrethroid resistance linked to control failure. Population structure analysis revealed a barrier to gene flow between southern Africa and other areas, which may prevent or slow the spread of the southern mechanism of pyrethroid resistance to other regions. By identifying a genetic signature of pyrethroid-based interventions, we have demonstrated the intense selective pressure that control interventions exert on mosquito populations. If this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised.
Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.|FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America.|Broad Institute, Cambridge, Massachusetts, United States of America.
Kayla G
0000-0002-8291-4388
KG
Barnes
Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Gareth D
GD
Weedall
Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Miranda
M
Ndula
Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Helen
H
Irving
Malaria Alert Centre, College of Medicine, University of Malawi, Blantyre, Malawi.
Themba
T
Mzihalowa
Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Janet
0000-0002-3200-7173
J
Hemingway
Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.|Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
Charles S
0000-0003-0791-3673
CS
Wondji
D000349:Africa; D000818:Animals; D000852:Anopheles / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D003577:Cytochrome P-450 Enzyme System / Q000145:classification / Q000235:genetics; D014644:Genetic Variation; D023281:Genomics; D006790:Host-Parasite Interactions / Q000187:drug effects; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D007303:Insect Vectors / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D010802:Phylogeny; D011722:Pyrethrins / Q000494:pharmacology*; D040641:Quantitative Trait Loci / Q000235:genetics; D012641:Selection, Genetic; D012689:Sequence Homology, Nucleic Acid
D019476:Insect Proteins; D007306:Insecticides; D011722:Pyrethrins; D003577:Cytochrome P-450 Enzyme System