Insecticide resistance in malaria vectors threatens to reverse recent gains in malaria control. Deciphering patterns of gene flow and resistance evolution in malaria vectors is crucial to improving control strategies and preventing malaria resurgence. A genome-wide survey of Anopheles funestus genetic diversity Africa-wide revealed evidences of a major division between southern Africa and elsewhere, associated with different population histories. Three genomic regions exhibited strong signatures of selective sweeps, each spanning major resistance loci ( CYP6P9a/b , GSTe2 and CYP9K1 ). However, a sharp regional contrast was observed between populations correlating with gene flow barriers. Signatures of complex molecular evolution of resistance were detected with evidence of copy number variation, transposon insertion and a gene conversion between CYP6P9a / b paralog genes. Temporal analyses of samples before and after bed net scale up suggest that these genomic changes are driven by this control intervention. Multiple independent selective sweeps at the same locus in different parts of Africa suggests that local evolution of resistance in malaria vectors may be a greater threat than trans-regional spread of resistance haplotypes. Author summary Malaria control currently relies heavily on insecticide-based vector control interventions. Unfortunately, resistance to insecticides is threatening their continued effectiveness. Metabolic resistance has the greatest operational significance, yet it remains unclear how mosquito populations evolutionarily respond to the massive selection pressure from control interventions including insecticide-treated nets. Deciphering patterns of gene flow between populations of major malaria vectors such as Anopheles funestus and elucidating genomic signature of resistance evolution are crucial for designing resistance management strategies and preventing malaria resurgence. Here, we performed a genome-wide survey of An . funestus genetic diversity from across its continental range using reduced-genome representation (ddRADseq) and whole genome (PoolSeq) approaches revealing evidence of significant barriers to gene flow impacting the spread of insecticide resistance alleles. This study detected signatures of strong selective sweeps occurring in genomic regions controlling cytochrome P450-based and glutathione s-transferase metabolic resistance to insecticides in this species. Fine-scale analysis of the major pyrethroid resistance-associated genomic regions revealed complex molecular evolution with evidence of copy number variation, transposon insertion and gene conversion highlighting the risk that if this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised.
【초록키워드】 Evolution, Variation, alleles, haplotypes, risk, Intervention, Local, molecular evolution, Population, malaria, Spread, management, Effectiveness, selection pressure, genetic diversity, molecular, genomic, Evidence, Analysis, selective sweep, evidence of, copy number, insecticide, insecticides, cytochrome P450, gene flow, glutathione, malaria control, gene conversion, bed net, metabolic, genomic region, locus, complex, insertion, loci, signature, Multiple, whole genome, pyrethroid, Metabolic resistance, selective sweeps, vector control, Genes, independent, greater, performed, approach, exhibited, analysis, driven by, malaria vector, respond, Temporal, transposon, highlighting, genomic change, Anophele, 【제목키워드】 Evolution, variations, genomic, copy number, insecticide, malaria vector, transposon, Anophele,