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


Autoři: Xavier Grau-Bové aff001;  Eric Lucas aff001;  Dimitra Pipini aff001;  Emily Rippon aff001;  Arjèn E. van ‘t Hof aff001;  Edi Constant aff002;  Samuel Dadzie aff003;  Alexander Egyir-Yawson aff004;  John Essandoh aff001;  Joseph Chabi aff003;  Luc Djogbénou aff001;  Nicholas J. Harding aff006;  Alistair Miles aff006;  Dominic Kwiatkowski aff006;  Martin J. Donnelly aff001;  David Weetman aff001
Působiště autorů: Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom aff001;  Centre Suisse de Recherches Scientifiques en Côte d’Ivoire, Abidjan, Côte d’Ivoire aff002;  Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana aff003;  Department of Biomedical Sciences, University of Cape Coast, Cape Coast, Ghana aff004;  Institut Régional de Santé Publique, Université d’Abomey-Calavi, Benin aff005;  Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom aff006;  Wellcome Sanger Institute, Hinxton, United Kingdom aff007
Vyšlo v časopise: Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus. PLoS Genet 17(1): e1009253. doi:10.1371/journal.pgen.1009253
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009253

Souhrn

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.

Klíčová slova:

Anopheles gambiae – Genomics – Ghana – Haplotypes – Insecticides – Introgression – Invertebrate genomics – Phylogenetic analysis


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