An Africa-wide genomic evolution of insecticide resistance in the malaria vector Anopheles funestus involves selective sweeps, copy number variations, gene conversion and transposons.

Gareth D Weedall,Helen Irving,Charles S Wondji,Bradley J White,Caroline Fouet,Jack Hearn,Colince Kamdem,Jacob M Riveron,Richard H Ffrench-Constant

doi:10.1371/journal.pgen.1008822

Abstract

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.

Highlights

Insecticide-based mosquito control has been hugely successful in reducing malaria globally [1] but has driven the evolution of insecticide resistance
Large-scale insecticide use creates strong selective pressures on mosquito populations to evolve resistance. This is made more likely by large effective population sizes and high levels of standing genetic diversity in mosquito populations [4]. Evidence of such evolution can be seen in the patterns of genetic diversity of mosquito populations, with selective sweeps reducing genetic diversity around loci associated with resistance [4,5,6]
In STRUCTURE analyses, the most likely number of clusters (K) was 2 (Malawi and Zambia in one, Ghana, Cameroon and Uganda in the other) and even for K>5 Malawi and Zambia were still assigned to one cluster, while Ghana, Cameroon and Uganda were each assigned to their own (Fig 1A)

Summary

Introduction

Insecticide-based mosquito control has been hugely successful in reducing malaria globally [1] but has driven the evolution of insecticide resistance. Large-scale insecticide use creates strong selective pressures on mosquito populations to evolve resistance. This is made more likely by large effective population sizes and high levels of standing genetic diversity in mosquito populations [4]. Patterns of resistance and underlying resistance mechanisms vary significantly between African regions [6, 12, 13] It remains to establish whether this is the result of different local selection pressures or the presence of strong barriers to gene flow between populations. Understanding the mechanisms of resistance and their potential to spread is a priority

Methods

Results

Conclusion