Regional adaptation to mosquito vectors shapes Plasmodium falciparum populations

Plasmodium falciparum , the most virulent human malaria parasite, is transmitted by Anopheles mosquitoes whose community composition varies geographically. Population genomic analyses reveal highly differentiated P. falciparum loci with roles in mosquito infection, which may be driven by adaptation to regional vectors. To test this, we generated transgenic parasites in which reference alleles were replaced with geographically alternative variants at candidate transmission-stage genes. Transmissibility was compared across four mosquito species representing distinct geographic ranges ( An. gambiae , An. stephensi , An. minimus , and An. albimanus ). Two of five tested polymorphisms increased oocyst and sporozoite burdens in sympatric parasite–vector combinations. Both substitutions occurred in ookinete micronemal proteins, CTRP and WARP, within von Willebrand factor A domains, suggesting that regional allelic variation modulates Plasmodium –vector compatibility by altering midgut adhesion interactions.