Identification of Novel Gene Cluster Potentially Associated with Insecticide Resistance in Anopheles gambiae s.l.

Background/Objectives: Despite the increasing emergence of resistance, insecticide-based tools remain the primary method for malaria vector control in Africa. To maintain the effectiveness of these interventions, continuous monitoring and identification of novel resistance mechanisms is essential. This study aimed to investigate potential new insecticide resistance genes in the Anopheles gambiae complex. Methods: We analyzed whole-genome sequencing data from the An. gambiae 1000 Genomes Project. A broad range of genomic analysis techniques and tools were used to identify and explore genetic variation in the candidate resistance genes. Results: High haplotype homozygosity values, indicative of positive selection, were detected in a 2L chromosomal region corresponding to an aldehyde oxidase gene cluster (AGAP006220, AGAP006221, AGAP006224, AGAP006225, AGAP006226). Single nucleotide polymorphisms (SNPs) have been identified in these genes with frequencies up to 100%, including 569, 691, 1433, 978, and 811 non-synonymous SNPs in AGAP006220, AGAP006221, AGAP006224, AGAP006225, and AGAP006226, respectively. Copy number variations (CNVs) such as deletions and amplifications were also identified at low frequencies (<12%). Population structure analyses revealed adaptive and geographic gene flow between An. gambiae and An. coluzzii. Conclusions: This study provides evidence that aldehyde oxidase genes may contribute to insecticide resistance in An. gambiae s.l. populations. These results highlight the importance of genomic surveillance for detecting novel resistance loci and guiding the development of improved vector control strategies under changing ecological and evolutionary conditions.