Genetic architectures of resistance to insecticides: from genomics to vectorial capacity – ArchR

To achieve these objectives, the ArchR project will rely on the wide diversity of resistance alleles with copy number variations found in the Culex pipiens mosquito, and on a unique collection of natural population samples collected over 30 years, combined with quantitative data on insecticide treatment variations. The ArchR project will also rely on a recognized international consortium, which has worked or is already working together on other projects, and which combines the complementary skills (population genetics, genomics and bioinformatics, molecular biology, vector competence and experimental infections, computer modeling, ...) and resources and infrastructure (insectariums level 2 and 3, molecular platforms and computer platforms) necessary to carry out this project. During this project, two PhD and several Master students will also be trained in high-level research with the different partners of this consortium.

The ArchR project will thus allow crucial developments for fundamental research in evolutionary biology: early evolution of duplications, impacts of adaptive dynamics on genome evolution, impact of environmental variations on genome polymorphism and population adaptability, evolutionary trade- offs between adaptation and transmission.

By linking the treatment practices with their demographic impacts and the dynamics of resistance alleles in natural populations, and by assessing the impact of resistance alleles on mosquito vectorial capacity, it will also provide useful information for professionals in charge of vector control or crop protection, and help design sustainable control strategies.

Milesi P., J.-L. Claret, S. Unal, M. Weill and P. Labbé. Evolutionary trade-offs associated with copy number variations in resistance alleles in Culex pipiens mosquitoes. submitted.

Since the middle of the 20th century, insecticides have been massively used to control the vectors of infectious diseases and thus limit their impact on public health. This drastic modification of their environment has selected different adaptations in these vectors, collectively referred to as insecticide resistance. The genomic architecture of these adaptations can be very diverse, ranging from simple nucleotide substitutions to large-scale mutations such as gene duplication. The effects of these different mutations on the vectors phenotype and fitness can differ and are difficult to anticipate, particularly in an environment that is itself variable.
Using interdisciplinary approaches, the ArchR project aims 1) to understand how these different genomic architectures impact the phenotype of their carriers, and to measure the evolutionary dynamics of multi-copy alleles under various intensities of insecticidal pressure in natura, 2) to study how variations in environmental conditions and the architecture of these adaptive mutations influence the dynamics of genome polymorphism, via the natural selection of resistance alleles and the demographic effects of insecticide treatments, and 3) to measure the effect of mutations on vectorial competence and mosquito metabolism, in order to anticipate their impact on public health.
To achieve these objectives, the ArchR project will rely on the wide diversity of resistance alleles with copy number variations found in the Culex pipiens mosquito, and on a unique collection of natural population samples collected over 30 years, combined with quantitative data on insecticide treatment variations. The ArchR project will also rely on a recognized international consortium, which has worked or is already working together on other projects, and which combines the complementary skills (population genetics, genomics and bioinformatics, molecular biology, vector competence and experimental infections, computer modeling, ...) and resources and infrastructure (insectariums level 2 and 3, molecular platforms and computer platforms) necessary to carry out this project. During this project, two PhD and several Master students will also be trained in high-level research with the different partners of this consortium.
The ArchR project will thus allow crucial developments for fundamental research in evolutionary biology: early evolution of duplications, impacts of adaptive dynamics on genome evolution, impact of environmental variations on genome polymorphism and population adaptability, evolutionary trade-offs between adaptation and transmission. By linking the treatment practices with their demographic impacts and the dynamics of resistance alleles in natural populations, and by assessing the impact of resistance alleles on mosquito vectorial capacity, it will also provide useful information for professionals in charge of vector control or crop protection, and help design sustainable control strategies.