title: Evidence for diversifying selection on erythrocyte-binding antigens of Plasmodium falciparum and P. vivax.
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 psieba-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.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom. jakebaum@pobox.com
authors.forename: Jake
authors.initials: J
authors.lastname: Baum
authors.forename: Alan W
authors.initials: AW
authors.lastname: Thomas
authors.forename: David J
authors.initials: DJ
authors.lastname: Conway
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D010966:Plasmodium vivax / Q000235:genetics* / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D000953:Antigens, Protozoan; D002352:Carrier Proteins; C438380:EBA140 protein, Plasmodium falciparum; D008565:Membrane Proteins; D015800:Protozoan Proteins; C065668:erythrocyte-binding antigen 175, Plasmodium