Multiple origins of knockdown resistance mutations in the Afrotropical mosquito vector Anopheles gambiae.
How often insecticide resistance mutations arise in natural insect populations is a fundamental question for understanding the evolution of resistance and also for modeling its spread. Moreover, the development of resistance is regarded as a favored model to study the molecular evolution of adaptive traits. In the malaria vector Anopheles gambiae two point mutations (L1014F and L1014S) in the voltage-gated sodium channel gene, that confer knockdown resistance (kdr) to DDT and pyrethroid insecticides, have been described. In order to determine whether resistance alleles result from single or multiple mutation events, genotyping of the kdr locus and partial sequencing of the upstream intron-1 was performed on a total of 288 A. gambiae S-form collected from 28 localities in 15 countries. Knockdown resistance alleles were found to be widespread in West Africa with co-occurrence of both 1014S and 1014F in West-Central localities. Differences in intron-1 haplotype composition suggest that kdr alleles may have arisen from at least four independent mutation events. Neutrality tests provided evidence for a selective sweep acting on this genomic region, particularly in West Africa. The frequency and distribution of these kdr haplotypes varied geographically, being influenced by an interplay between different mutational occurrences, gene flow and local selection. This has important practical implications for the management and sustainability of malaria vector control programs.
Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Lisbon, Portugal. jpinto@ihmt.unl.pt
João
J
Pinto
Amy
A
Lynd
José L
JL
Vicente
Federica
F
Santolamazza
Nadine P
NP
Randle
Gabriele
G
Gentile
Marta
M
Moreno
Frédéric
F
Simard
Jacques Derek
JD
Charlwood
Virgílio E
VE
do Rosário
Adalgisa
A
Caccone
Alessandra
A
Della Torre
Martin J
MJ
Donnelly
D000818:Animals; D000852:Anopheles / Q000187:drug effects / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D009154:Mutation
D017931:DNA Primers