A rapidly selected 4.3kb transposon-containing structural variation is
driving a P450-based resistance to pyrethroids in the African malaria
vector Anopheles funestus
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/b but 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.