Vector Biology Department, Liverpool School of Tropical Medicine (LSTM), Pembroke Place, Liverpool, United Kingdom.
School of Biological and Environmental Sciences, Liverpool John Moores University, Liverpool, United Kingdom.
PLoS Genet. 2020 Jun 4;16(6):e1008822. doi: 10.1371/journal.pgen.1008822. eCollection 2020 Jun.
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.
杀虫剂对疟疾媒介的抗药性威胁到最近在疟疾控制方面取得的进展。解析疟疾媒介中基因流动和抗药性进化的模式对于改进控制策略和防止疟疾死灰复燃至关重要。对非洲范围内的致倦库蚊遗传多样性进行的全基因组调查显示，南部非洲与其他地区之间存在着一个主要的分裂，这与不同的种群历史有关。三个基因组区域表现出强烈的选择清除信号，每个区域跨越主要的抗性基因座（CYP6P9a/b、GSTe2 和 CYP9K1）。然而，在与基因流动障碍相关的种群之间观察到了明显的区域对比。检测到抗性复杂分子进化的特征，包括基因拷贝数变异、转座子插入和 CYP6P9a/b 基因座的基因转换。在蚊帐规模扩大前后的样本时间分析表明，这些基因组变化是由这种控制干预驱动的。在非洲不同地区的同一基因座上发生的多个独立的选择清除表明，疟疾媒介中局部的抗药性进化可能比抗性单倍型的跨区域传播更具威胁。
