Role of in the dispersal of ancestral malaria through adaptation to different anopheline vectors.

malaria originated when , a gorilla malaria parasite transmitted by African sylvan anopheline mosquitoes, adapted to humans. Pfs47, a protein on the parasite surface mediates evasion of the mosquito immune system by interacting with a midgut receptor and is critical for adaptation to different anopheline species. Genetic analysis of 4,971 gene sequences from different continents revealed that Asia and Papua New Guinea harbor haplotypes more similar to its ortholog in at sites that determine vector compatibility, suggesting that ancestral readily adapted to Asian vectors. Consistent with this observation, Pfs47-receptor gene sequences from African sylvan malaria vectors, such as and , were found to share greater similarity with those of vectors than those of vectors of the African complex. Furthermore, experimental infections provide direct evidence that transformed parasites carrying orthologs of or were more effective at evading the immune system of the Asian malaria vector than . We propose that high compatibility of ancestral Pfs47 with the receptors of Asian vectors facilitated the early dispersal of human malaria to the Asian continent, without having to first adapt to sub-Saharan vectors of the complex.