Despite structural identity, ace-1 heterogenous duplication resistance alleles are quite diverse in Anopheles mosquitoes

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Claret, Jean-Loup | Di-Liegro, Marion | Namias, Alice | Assogba, Benoit | Makoundou, Patrick | Koffi, Alphonsine | Pennetier, Cedric | Weill, Mylène | Milesi, Pascal | Labbé, Pierrick

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International audience. Anopheles gambiae s.l . has been the target of intense insecticide treatment since the mid-20th century to try and control malaria. A substitution in the ace-1 locus has been rapidly selected for, allowing resistance to organophosphate and carbamate insecticides. Since then, two types of duplication of the ace-1 locus have been found in An. gambiae s.l . populations: homogeneous duplications that are composed of several resistance copies, or heterogeneous duplications that contain both resistance and susceptible copies. The substitution induces a trade-off between resistance in the presence of insecticides and disadvantages in their absence: the heterogeneous duplications allow the fixation of the intermediate heterozygote phenotype. So far, a single heterogeneous duplication has been described in An. gambiae s.l . populations (in contrast with the multiple duplicated alleles found in Culex pipiens mosquitoes). We used a new approach, combining long and short-read sequencing with Sanger sequencing to precisely identify and describe at least nine different heterogeneous duplications, in two populations of An. gambiae s.l . We show that these alleles share the same structure as the previously identified heterogeneous and homogeneous duplications, namely 203-kb tandem amplifications with conserved breakpoints. Our study sheds new light on the origin and maintenance of these alleles in An. gambiae s.l . populations, and their role in mosquito adaptation.

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