Whole-genome sequencing of major malaria vectors reveals the evolution of new insecticide resistance variants in a longitudinal study in Burkina Faso

Intensive deployment of insecticide based malaria vector control tools results in the rapid evolution of phenotypes resistant to these chemicals. Understanding this process on the genomic level is essential for the deployment of successful interventions. Using whole genome sequencing data of 1409 individual An. Gambiae s.l. collected from 2012 to 2017, we investigated the change in genetic structure and the evolution of the insecticide resistance variants in natural populations over time and space. The results showed similar and constant nucleotide diversity and negative Tajimas D between An. gambiae s.s. and An. coluzzii. PCA and FST showed a clear genetic structure in the An. gambiae s.l. species. Genome-wide FST and H12 scans identified genomic regions under divergent selection and also having an implication in the adaptations to ecological changes. Novel voltage-gated sodium channel pyrethroid resistance target-site alleles (V402L, I1527T) were identified at increasing frequencies alongside the established kdr alleles (Vgsc-L995F, Vgsc-L995S and N1570Y) within the An. gambiae s.l. populations. Organophosphate metabolic resistance markers were also identified, at increasing frequencies, within the An. gambiae s.s. populations from 2012 to 2017, including the SNP Ace1-G280S and its associated duplication. Variants simultaneously identified in the same vector populations raise concerns about the long-term efficacy of new-generation bednets and the recently introduced organophosphate pirimiphos-methyl indoor residual spraying. These findings highlighted the benefit of genomic malaria vector surveillance for the detection of new insecticide resistance variants, the monitoring of the existing resistance variants, and also to get insights into the evolutionary processes driving insecticide resistance. Author SummaryGenomic surveillance of malaria vectors is crucial for understanding the genetic variation in natural vector populations and also guiding the implementation of novel and innovative vector control tools. Application of sequencing technologies in vector studies provide insights on the genetic and evolutionary phenomena of vectors that could have impact on vector control strategies. By analyzing the whole genome data of 1409 wild An. gambiae s.l. mosquito collected between 2012 and 2017, we showed an emergence of novel insecticide resistance markers alongside increasing frequencies of existing insecticide resistance variants over time in Burkina Faso. We showed the benefit of genomic surveillance of malaria vectors for the monitoring of the insecticide resistance variants and also providing insights into the evolutionary processes driving insecticide resistance.