Genomic analysis identifies candidate supergene architecture for host-feeding behavior in wild Aedes aegypti dengue...

Aedes aegypti is the primary arboviral vector globally, and its affinity to feed on human hosts is a key determinant of transmission intensity. Despite the epidemiological importance of anthropophily, the genomic architecture underlying the molecular basis of host-feeding behavior remains understudied.

Here, we present an integrated genome-wide association study (GWAS) and structural variant analysis of host-feeding behavior in 21 field-collected Ae. aegypti females phenotyped as human-blood-fed (HF; n = 11) or non-human-blood-fed (NHF; n = 10). Whole-genome sequencing yielded 661,519 high-quality SNPs distributed across all three chromosomes. Principal component analysis on a linkage disequilibrium-pruned dataset revealed modest population structure (PC1 = 11.69%, PC2 = 10.98%).

GWAS using a general linear model with five PC covariates (λ = 1.05) identified 11 suggestive SNPs in genes including an actin binding protein on chromosome 2 and G-protein coupled receptor 39 on chromosome 3. Chromosomal inversion analysis using Delly identified an HF-specific inversion on chromosome 2 harboring 13 genes across three functionally coherent chemosensory categories: the sensory developmental regulator tap, odorant receptors (Or6, Or31, Or33) and an odorant-binding protein (Gp68), and eight gustatory receptor genes (Gr15-Gr19a, Gr35, Gr36, Gr66).

The concentration of co-adapted chemosensory genes within a single non-recombining chromosomal unit is consistent with a possible supergene model of anthropophily, paralleling inversion-mediated behavioral divergence in Anopheles gambiae. These exploratory findings provide a preliminary genomic framework for host-seeking behavior in Ae. aegypti and identify probable candidate loci warranting functional validation before application to vector surveillance.