Role of <i>Pfs47</i> in the dispersal of ancestral <i>Plasmodium falciparum</i> malaria through adaptation to different anopheline vectors.

Abstract

<i>Plasmodium falciparum</i> malaria originated when <i>Plasmodium praefalciparum</i>, a gorilla malaria parasite transmitted by African sylvan anopheline mosquitoes, adapted to humans. Pfs47, a protein on the parasite surface mediates <i>P. falciparum</i> evasion of the mosquito immune system by interacting with a midgut receptor and is critical for <i>Plasmodium</i> adaptation to different anopheline species. Genetic analysis of 4,971 <i>Pfs47</i> gene sequences from different continents revealed that Asia and Papua New Guinea harbor <i>Pfs47</i> haplotypes more similar to its ortholog in <i>P. praefalciparum</i> at sites that determine vector compatibility, suggesting that ancestral <i>P. falciparum</i> readily adapted to Asian vectors. Consistent with this observation, Pfs47-receptor gene sequences from African sylvan malaria vectors, such as <i>Anopheles moucheti</i> and <i>An. marshallii</i>, were found to share greater similarity with those of <i>Asian</i> vectors than those of vectors of the African <i>An. gambiae</i> complex. Furthermore, experimental infections provide direct evidence that transformed <i>P. falciparum</i> parasites carrying <i>Pfs47</i> orthologs of <i>P. praefalciparum</i> or <i>P. reichenowi</i> were more effective at evading the immune system of the Asian malaria vector <i>An. dirus</i> than <i>An. gambiae</i>. We propose that high compatibility of ancestral <i>P. falciparum</i> 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 <i>An. gambiae</i> complex.