title: Contrasting signatures of selection on the Plasmodium falciparum erythrocyte binding antigen gene family.
abstract: Erythrocyte binding antigens of Plasmodium falciparum are involved in erythrocyte invasion, and may be targets of acquired immunity. Of the five eba genes, protein products have been detected for eba-175, eba-181 and eba-140, but not for psieba-165 or ebl-1, providing opportunity for comparative analysis of genetic variation to identify selection. Region II of each of these genes was sequenced from a cross-sectional sample of parasites in an endemic Kenyan population, and the frequency distributions of polymorphisms analysed. A positive value of Tajima's D was observed for eba-175 (D=1.13) indicating an excess of intermediate frequency polymorphisms, while all other genes had negative values, the most negative being ebl-1 (D=-2.35) followed by psieba-165 (D=-1.79). The eba-175 and ebl-1 genes were then studied in a sample of parasites from Thailand, for which a positive Tajima's D value was again observed for eba-175 (D=1.79), and a negative value for ebl-1 (D=-1.85). This indicates that eba-175 is under balancing selection in each population, in strong contrast to the other members of the gene family, particularly ebl-1 and psieba-165 that may have been under recent directional selection. Population expansion simulations were performed under a neutral model, further supporting the departures from neutrality of these genes.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. federica.verra@lshtm.ac.uk
authors.forename: Federica
authors.initials: F
authors.lastname: Verra
authors.forename: Watcharee
authors.initials: W
authors.lastname: Chokejindachai
authors.forename: Gareth D
authors.initials: GD
authors.lastname: Weedall
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Polley
authors.forename: Tabitha W
authors.initials: TW
authors.lastname: Mwangi
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: David J
authors.initials: DJ
authors.lastname: Conway
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics*; D001483:Base Sequence; D016054:DNA, Protozoan / Q000235:genetics; D017125:Genes, Protozoan; D014644:Genetic Variation; D006801:Humans; D007630:Kenya; D015810:Linkage Disequilibrium; D016778:Malaria, Falciparum / Q000469:parasitology; D008969:Molecular Sequence Data; D005810:Multigene Family; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D011995:Recombination, Genetic; D012641:Selection, Genetic; D012689:Sequence Homology, Nucleic Acid
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; C066001:Duffy antigen binding protein, Plasmodium; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface