Bacot, T. | bioRxiv Science

bioRxiv2025

Metabolic resistance of the tiger mosquito to pyrethroid insecticides in La Reunion Island likely results from local adaptation

The resistance of mosquitoes to insecticides is a valuable model system for studying the genetic bases of xenobiotic adaptation in insects. The spread of the Asian tiger mosquito Aedes albopictus combined to the massive use of pyrethroid insecticides to limit arbovirus transmission resulted in the rise of resistance in various continents. Here, we investigated the genetic mechanisms underlying the recent adaptation of this mosquito to deltamethrin in La Reunion island. Bioassays confirmed the presence of resistance alleles in field populations. The resistance phenotype was further enhanced in the laboratory following a few generations of controlled selection. Combining whole genome Pool-seq and RNA-seq revealed no evidence of target-site resistance mutations but the over-expression and variant selection of detoxification enzymes associated with pyrethroid metabolism including cytochrome P450s, transferases and ABC-transporters. Among over-expressed detoxification genes, only one was linked to a gene duplication while polymorphism data suggest most of them being trans-regulated. Genome-wide selection signatures revealed a 9 Mb inverted superlocus responding to insecticide selection whose phenotypical importance remains uncertain. Altogether, this study indicates that the multigenic metabolic resistance phenotype observed in this insular territory mainly results from local adaptation. From an applied perspective, this study provides a set of markers to track pyrethroid resistance in the tiger mosquito in the South-West Indian Ocean. As this region is subjected to recurrent arbovirus outbreaks, the additive resistance phenotype that may arise from the introduction of Kdr mutations from other territories also calls for improving resistance surveillance at the regional scale. Author summaryWhile novel vector control strategies are being developed, chemical insecticides remain widely used to control mosquitoes transmitting human diseases such as the Asian tiger mosquito. However, the recurrent use of insecticides resulted in the emergence of resistance which can ultimately affect vector control efficacy. Here, we investigate the genetic bases underlying the resistance of the Asian tiger mosquito to the pyrethroid insecticide deltamethrin in La Reunion island. By combining two complementary genomic approaches, we showed that resistance is mainly caused by an increased insecticide detoxification while classical Knock down resistance mutations affecting the target of the insecticide were not detected. We also showed that resistance is underlain by multiple genetic changes spread across the genome, supporting the local selection of resistance rather than the introduction of resistance alleles. Furthermore, we identified a large inverted supergene responding to insecticide selection. This study provides valuable insights into the genetic bases of insecticide resistance, enabling the implementation of molecular makers to improve the tracking of insecticide resistance in this major mosquito vector across the Indian Ocean.

genomics↗

bioRxiv2024

A genomic duplication spanning multiple P450s contributes to insecticide resistance in the dengue mosquito Aedes aegypti

Resistance of mosquitoes to insecticides is one example of rapid adaptation to anthropogenic selection pressures having a strong impact on human health and activities. Target-site modification and increased insecticide detoxification are the two main mechanisms underlying insecticide resistance in mosquitoes. While target-sites mutations are well characterised and often used to track resistance in the field, the genomic events associated with insecticide detoxification remain partially characterised. Recent studies evidenced the key role of gene duplications in the over-expression of detoxification enzymes and their potential use to track metabolic resistance alleles in the field. However, such genomic events remain difficult to characterise due to their complex genomic architecture and their co-occurrence with other resistance alleles. In this concern, the present work investigated the role of a large genomic duplication affecting a cluster of detoxification enzymes in conferring resistance to the pyrethroid insecticide deltamethrin in the mosquito Aedes aegypti. Two isofemale lines originating from French Guiana and being deprived from major target-site mutations showed distinct insecticide resistance levels. Combining RNA-seq and whole genome pool-seq identified a 220 Kb genomic duplication enhancing the expression of multiple contiguous cytochrome P450s in the resistant line. The genomic architecture of the duplicated loci was elucidated through long read sequencing, evidencing its transposon-mediated evolutionary origin. The involvement of this P450 duplication in deltamethrin survival was supported by a significant phenotypic response to the P450 inhibitor piperonyl butoxide together with genotype-phenotype association and RNA interference. Experimental evolution suggested that this P450 duplication is associated with a significant fitness cost, potentially affecting its adaptive value in presence of other resistance alleles. Overall, this study supports the importance of genomic duplications affecting detoxification enzymes in the rapid adaptation of mosquitoes to insecticides. Deciphering their genomic architecture provides new insights into the evolutionary processes underlying such rapid adaptation. Such findings provide new tools for the surveillance and management of resistance in the field.

evolutionary biology↗