Genomic population structure and insecticide resistance mechanisms in the malaria vector An. coluzzii across contrasting bioclimatic zones in West Africa

Environmental barriers influencing the movement of insect vectors can govern adaptive gene flow, including the dispersal of insecticide resistance mechanisms that compromise population control. We sought to understand population connectivity of the major malaria vector, An. coluzzii, across the different bioclimatic zones of West Africa including Ghana, Mali and Côte d’Ivoire using SNPs from whole genomes and inversion karyotypes previously associated with environmental adaptation. We used Ghana as a case study to investigate how adaptive alleles are shared across geographical space. Paired-end 100–150 bp sequencing reads were aligned to the AgamP4 reference genome using BWA version 0.7.15 and single nucleotide polymorphisms (SNP) called using GATK version 3.7.0. We characterised known target site and metabolic insecticide resistance markers, including amino acid substitutions and copy number variants. We also performed genome-wide scans for novel signals of selection with a potential link to insecticide resistance using the H12 homozygosity statistic across defined windows of the genome. Based on analysis of population connectivity, we identified restricted gene flow between An. coluzzii from the northern savannah and southern forested regions of West Africa. We further found marked differences in insecticide resistance profiles across the different bioclimatic zones in Ghana, suggesting that population connectivity impacts on adaptive allele sharing. Greater evidence for target site pyrethroid resistance substitutions at the Vgsc gene and metabolic resistance markers at carboxylesterases and Gste2 in the North reflected differences in insecticide use across the country. Based on insecticide resistance marker profiles and selection scans, we also observed distinct resistance mechanisms in the coastal region of Greater Accra which may result from intense urban agricultural activity. These included a unique selection signal on the 3R chromosome at a cytochrome P450 gene, Cyp12f and a UDP glucuronosyltransferase. Overall, findings suggest that environmental conditions restrict An. coluzzii gene flow to impact the geographical distribution of molecular insecticide resistance.