Abstract:
Deciphering the evolutionary forces controlling insecticide resistance
in malaria vectors remains a prerequisite to designing molecular tools
to detect and assess resistance impact on control tools. Here, we
demonstrate that a 4.3kb transposon-containing structural variation
drives pyrethroid resistance in central/eastern African populations of
the malaria vector Anopheles funestus . In this study, we analysed
Pooled template sequencing data and direct sequencing to identify an
insertion of 4.3kb containing putative transposons in the intergenic
region of two P450s CYP6P5 -CYP6P9b in mosquitoes of the
malaria vector Anopheles funestus from Uganda. We then designed a
PCR assay to track its spread temporally and regionally and decipher its
role in insecticide resistance. The insertion originates in or near
Uganda in East Africa, where it is fixed and has spread to high
frequencies in the Central African nation of Cameroon but is still at
low frequency in West Africa and absent in Southern Africa. A strong
association was established between this SV and pyrethroid resistance in
field populations (SV+ vs SV-; OR=29, P < 0.0001) and is
reducing pyrethroid-only nets’ efficacy. Genetic crosses and qRT-PCR
revealed that this SV enhances the overexpression of CYP6P9a/bbut not CYP6P5 . A marked and rapid selection was observed with
the 4.3kb-SV frequency increasing from 3% in 2014 to 98 % in 2021 in
Cameroon. Our findings highlight the underexplored role and rapid spread
of SVs in the evolution of insecticide resistance and provide additional
tools for molecular surveillance of insecticide resistance.