Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus.

Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highl...

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Main Authors: Xavier Grau-Bové, Eric Lucas, Dimitra Pipini, Emily Rippon, Arjèn E van 't Hof, Edi Constant, Samuel Dadzie, Alexander Egyir-Yawson, John Essandoh, Joseph Chabi, Luc Djogbénou, Nicholas J Harding, Alistair Miles, Dominic Kwiatkowski, Martin J Donnelly, David Weetman, Anopheles gambiae 1000 Genomes Consortium
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1009253
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author Xavier Grau-Bové
Eric Lucas
Dimitra Pipini
Emily Rippon
Arjèn E van 't Hof
Edi Constant
Samuel Dadzie
Alexander Egyir-Yawson
John Essandoh
Joseph Chabi
Luc Djogbénou
Nicholas J Harding
Alistair Miles
Dominic Kwiatkowski
Martin J Donnelly
David Weetman
Anopheles gambiae 1000 Genomes Consortium
author_facet Xavier Grau-Bové
Eric Lucas
Dimitra Pipini
Emily Rippon
Arjèn E van 't Hof
Edi Constant
Samuel Dadzie
Alexander Egyir-Yawson
John Essandoh
Joseph Chabi
Luc Djogbénou
Nicholas J Harding
Alistair Miles
Dominic Kwiatkowski
Martin J Donnelly
David Weetman
Anopheles gambiae 1000 Genomes Consortium
author_sort Xavier Grau-Bové
collection DOAJ
description Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Côte d'Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions.
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spelling doaj-art-30c7338ad0d441db8220b06ca1885bfa2025-08-20T02:23:18ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-01-01171e100925310.1371/journal.pgen.1009253Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus.Xavier Grau-BovéEric LucasDimitra PipiniEmily RipponArjèn E van 't HofEdi ConstantSamuel DadzieAlexander Egyir-YawsonJohn EssandohJoseph ChabiLuc DjogbénouNicholas J HardingAlistair MilesDominic KwiatkowskiMartin J DonnellyDavid WeetmanAnopheles gambiae 1000 Genomes ConsortiumVector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Côte d'Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions.https://doi.org/10.1371/journal.pgen.1009253
spellingShingle Xavier Grau-Bové
Eric Lucas
Dimitra Pipini
Emily Rippon
Arjèn E van 't Hof
Edi Constant
Samuel Dadzie
Alexander Egyir-Yawson
John Essandoh
Joseph Chabi
Luc Djogbénou
Nicholas J Harding
Alistair Miles
Dominic Kwiatkowski
Martin J Donnelly
David Weetman
Anopheles gambiae 1000 Genomes Consortium
Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus.
PLoS Genetics
title Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus.
title_full Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus.
title_fullStr Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus.
title_full_unstemmed Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus.
title_short Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus.
title_sort resistance to pirimiphos methyl in west african anopheles is spreading via duplication and introgression of the ace1 locus
url https://doi.org/10.1371/journal.pgen.1009253
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