Genomic Connectivity and Adaptive Gene Flow of Anopheles gambiae s. s. Across East and Central Africa.

Population connectivity influences the adaptive capacity of disease vectors by mediating the spread of insecticide resistance alleles. High gene flow poses challenges for tailored intervention strategies targeting localised populations, but connectivity is often poorly characterised for particular geographical regions. This study uses whole-genome data to investigate the population connectivity of the Anopheles gambiae malaria vector across East-Central Africa, including understudied populations from Ethiopia. We also investigated adaptive gene flow using Diplotype clustering at known insecticide resistance loci. Population structure analyses revealed that Ethiopian populations experience high gene flow with inland East African An. gambiae including Uganda, inland Kenya, inland Tanzania, and the northern DRC, likely reflecting ecological continuity across the region. In contrast, coastal populations of East Africa and south-central DRC were subject to restricted gene flow, consistent with geographical and ecological barriers to dispersal. Diplotype clustering of the Cyp6aa/p gene cluster and Cyp9k1 revealed that CNV-variant sharing broadly mirrored genome-wide connectivity patterns, with shared variation present in inland East Africa and the northern DRC, but distinct CNV-associated clusters in more isolated populations in southeastern DRC. On the other hand, allele sharing at the Vgsc gene did not follow patterns of population connectivity, with the Vgsc -L995S allele broadly shared across East Africa and the Vgsc -L995F allele shared between Ethiopia and populations throughout the DRC. Notably, Ethiopia emerges as a crossover point where resistance alleles from East and Central Africa can converge, suggesting it is an important region for the monitoring of emergent and/or expanding adaptations. Findings highlight the importance of cross-border collaboration and the development of resistance management strategies that respond to both regional connectivity and local divergence.