Copy number variants underlie major selective sweeps in insecticide resistance genes in Anopheles arabiensis.

Autor: Lucas ER; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Nagi SC; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Kabula B; National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania., Batengana B; National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania., Kisinza W; National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania., Egyir-Yawson A; Department of Biomedical Sciences, University of Cape Coast, Cape Coast, Ghana., Essandoh J; Department of Biomedical Sciences, University of Cape Coast, Cape Coast, Ghana., Dadzie S; Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana., Chabi J; Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana., Van't Hof AE; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.; Biology Centre of the Czech Academy of Sciences, Institute of Entomology, České Budějovice, Czech Republic., Rippon EJ; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Pipini D; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Harding NJ; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom., Dyer NA; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Clarkson CS; Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom., Miles A; Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom., Weetman D; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Donnelly MJ; Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.; Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2024 Dec 05; Vol. 22 (12), pp. e3002898. Date of Electronic Publication: 2024 Dec 05 (Print Publication: 2024).
DOI: 10.1371/journal.pbio.3002898
Abstrakt: To keep ahead of the evolution of resistance to insecticides in mosquitoes, national malaria control programmes must make use of a range of insecticides, both old and new, while monitoring resistance mechanisms. The outdoor-biting malaria vector Anopheles arabiensis is of increasing concern for malaria transmission because it is apparently less susceptible to many indoor control interventions, yet knowledge of its mechanisms of resistance remains limited. Furthermore, comparatively little is known in general about resistance to non-pyrethroid insecticides such as pirimiphos-methyl (PM), which are crucial for effective control in the context of globally high resistance to pyrethroids. We performed a genome-wide association study to determine the molecular mechanisms of resistance to the pyrethroid deltamethrin (commonly used in bednets) and PM (widespread use for indoor spraying), in An. arabiensis from 2 regions in Tanzania. Genomic regions of positive selection in these populations were largely driven by copy number variants (CNVs) in gene families involved in metabolic resistance. We found evidence of a new gene cluster involved in resistance to PM, identifying a strong selective sweep tied to a CNV in the carboxylesterase genes Coeae2g - Coeae6g. Using complementary data from another malaria vector, An. coluzzii, in Ghana, we show that copy number at this locus is significantly associated with PM resistance. Similarly, for deltamethrin, resistance was strongly associated with a novel CNV allele in the Cyp6aa / Cyp6p cluster (Cyp6aap_Dup33). Against this background of metabolic resistance, resistance caused by mutations in the insecticide target sites was very rare or absent. Mutations in the pyrethroid target site Vgsc were at very low frequency in Tanzania, yet combining these samples with 3 An. arabiensis individuals from West Africa revealed a startling evolutionary diversity, with up to 5 independent origins of Vgsc-995 mutations found within just 8 haplotypes. Thus, despite having been first recorded over 10 years ago, Vgsc resistance mutations in Tanzanian An. arabiensis have remained at stable low frequencies. Overall, our results provide a new copy number marker for monitoring resistance to PM in malaria mosquitoes, and reveal the complex picture of resistance patterns in An. arabiensis.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Lucas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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