Multi-locus investigation of Anopheles-mediated selective pressure on Plasmodium falciparum in Africa.

BACKGROUND

The high burden of malaria in Africa is largely due to the presence of competent and adapted vector species. With invasive implicated in malaria outbreaks in Africa, understanding the genomic basis of vector-parasite compatibility is essential for assessing the risk of future outbreaks due to this mosquito. Vector compatibility with arises from ancient coevolution and involves genes like in and P47Rec in . Questions remain about whether sub-continental vector variation is a selective pressure on current populations or not.

METHODS

We analyzed the genetic diversity in parasite-vector interaction genes in and from 9 and 15 countries in Africa, respectively. Specifically, we looked for evidence of malaria vector-mediated selection within three genes and conducted association analyses with occurrence probabilities of prominent malaria vectors (VOP).

RESULTS

Higher protein haplotype diversities of Pfs47 and Pfs16 were associated with the probability of occurrence of and together. Only carried a signature of positive selection consistently (average Tajima's D = -2.96) which was associated with the probability of occurrence of . These findings support vector-mediated selection based on vector species diversity may be occurring within Africa. We also employed phylogenetic analyses of interaction genes (, , ) to identify significant subspecies diversity as a prerequisite to vector-population-mediated selection. HPX15 revealed significant sub-species differentiation (multiple branches bootstrap >70) compared to absence of variation in P47Rec, suggesting further investigation into sub-species mediated selection based on HPX15 is needed. Finally, we observed five amino acid changes at P47Rec in invasive compared to dominant African species, calling for further investigation of the impact these distinct P47Rec variants would have on local African Pfs47 diversity.

CONCLUSION

Overall, these findings support the notion that vector variation within Africa could influence diversity and lay a genomic framework for future investigation of invasive impact on African malaria.