Evidence for Diversifying Selection on Erythrocyte-Binding Antigens of Plasmodium falciparum and P. vivax

Genetics - Tập 163 Số 4 - Trang 1327-1336 - 2003
Jake Baum1, Alan W. Thomas2, David J. Conway1
1Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom
2Department of Parasitology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands

Tóm tắt

Abstract Malaria parasite antigens involved in erythrocyte invasion are primary vaccine candidates. The erythrocyte-binding antigen 175K (EBA-175) of Plasmodium falciparum binds to glycophorin A on the human erythrocyte surface via an N-terminal cysteine-rich region (termed region II) and is a target of antibody responses. A survey of polymorphism in a malaria-endemic population shows that nucleotide alleles in eba-175 region II occur at more intermediate frequencies than expected under neutrality, but polymorphisms in the homologous domains of two closely related genes, eba-140 (encoding a second erythrocyte-binding protein) and Ψeba-165 (a putative pseudogene), show an opposite trend. McDonald-Kreitman tests employing interspecific comparison with the orthologous genes in P. reichenowi (a closely related parasite of chimpanzees) reveal a significant excess of nonsynonymous polymorphism in P. falciparum eba-175 but not in eba-140. An analysis of the Duffy-binding protein gene, encoding a major erythrocyte-binding antigen in the other common human malaria parasite P. vivax, also reveals a significant excess of nonsynonymous polymorphisms when compared with divergence from its ortholog in P. knowlesi (a closely related parasite of macaques). The results suggest that EBA-175 in P. falciparum and DBP in P. vivax are both under diversifying selection from acquired human immune responses.

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