Brenas, J. H. | bioRxiv Science

bioRxiv2026

Genomic signatures of selection in Anopheles funestus reveal shared and population-specific adaptive variation across African populations

Insecticide resistance in Anopheles funestus threatens malaria vector control across sub-Saharan Africa, yet genomic signatures of selection across geographically structured populations remain poorly understood. We analysed whole-genome sequence data from 635 An. funestus mosquitoes from West (Senegal, Guinea, Nigeria), Central (Cameroon), and East Africa (Kenya) to characterise population structure and identify targets of recent positive selection. Population genomic analyses revealed strong differentiation between East African and West/Central African populations, with finer-scale structuring within West Africa. Genome-wide selection scans using H12 identified sweep regions on chromosome arms 2RL and 3RL, overlapping a cytochrome P450 cluster and the gamma-aminobutyric acid (GABA) receptor locus respectively. iSAFE prioritised candidate variants within these sweeps: non-synonymous substitutions in CYP6A14 were identified at high frequencies in Guinea, Nigeria, and Cameroon, while population-restricted variants implicated octopamine receptor genes on 2RL and the GABA receptor on 3RL. Diplotype clustering and copy number variation analyses confirmed the causal role of candidate variants, embedded within extended haplotypes of reduced heterozygosity consistent with recent positive selection. These findings demonstrate that adaptive evolution in An. funestus reflects both shared and population-specific selective processes shaped by geography and ecological context. Whereas selection on detoxification pathways appears widespread, localised signals in neuromodulatory loci, including the GABA receptor and octopamine-related genes, reveal that biological systems beyond metabolic resistance contribute to mosquito adaptation. The convergence of selective signals across these gene classes highlights neuromodulatory pathways as potential complementary targets for next-generation vector control strategies.

genomics↗

bioRxiv2023

Mechanisms of transcriptional regulation in Anopheles gambiae revealed by allele specific expression

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in cis, by regulatory sequences on the same chromosome, and by trans acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in cis-regulatory modules (CRM), but few of these have been identified in mosquitoes. We crossed bendiocarb resistant and susceptible Anopheles gambiae strains to identify cis-regulated genes that might be responsible for the resistant phenotype using RNAseq, and cis-regulatory module sequences controlling gene expression in insecticide resistance relevant tissues were predicted using machine learning. We found 115 genes showing allele specific expression in hybrids of insecticide susceptible and resistant strains, suggesting cis regulation is an important mechanism of gene expression regulation in Anopheles gambiae. The genes showing allele specific expression included a higher proportion of Anopheles specific genes on average younger than genes those with balanced allelic expression. Author SummaryThe evolution of insecticide resistance, including resistance that is due to changes in the expression levels of certain resistance associated genes is threatening progress in malaria control. We investigated how the expression of genes in the malaria vector Anopheles gambiae is controlled, by implementing a method for the first time in this species. Each mosquito inherits a set of chromosomes from both parents, so has a maternal and paternal copy of most genes. When a gene is expressed, the DNA encoding that gene is transcribed into messenger RNA. This process is controlled by the cellular environment and by other DNA sequences on the same chromosome as each gene. We crossed mosquitoes from insecticide resistant and susceptible strains to equalize the cellular environment and then measured the levels of messenger RNA from both gene copies. 115 genes showed consistently different messenger RNA levels between gene copies in most crosses, suggesting these genes are regulated by factors on the same chromosome. There were relatively more Anopheles specific genes with imbalanced expression. Using machine learning we identified DNA sequences that may be responsible for controlling gene expression in mosquito tissues; several of these sequences were close to genes with imbalanced expression.

genetics↗