title: Natural selection on Plasmodium surface proteins.
abstract: Numbers of synonymous (ds) and nonsynonymous (dN) nucleotide substitutions per site were analysed in eight polymorphic Plasmodium genes: circumsporozoite protein gene (CSP), sporozoite surface protein 2 (thrombospondin related anonymous protein, TRAP), merozoite surface antigen 2 (MSA-2), apical membrane antigen 1 (PF83), liver-stage antigen-1 (LSA-1), knob-associated histidine-rich protein (KAHRP), ring-infected erythrocyte surface antigen (RESA) and S-antigen. In certain regions of genes coding for proteins of the sporozoite and merozoite surface (CSP, TRAP, MSA-2 and PF83), dN was significantly greater than dS. This unusual pattern of nucleotide substitution is indicative of positive Darwinian selection acting to promote diversity at the amino-acid level; thus our results suggest that the sporozoite and merozoite surface proteins are under positive selection, presumably exerted by the host immune system. No such pattern of substitution was observed on LSA-1, KAHRP, RESA, or S-antigen. Observed patterns of nucleotide substitution were not explicable by nucleotide content bias. G + C content in the 5' nonrepeat region of CSP in nine Plasmodium species was positively correlated with that in the 3' nonrepeat region; however, there was no relationship between G + C content and the ratio dS/dN in either CSP or a larger sample of all regions of all genes analysed.
authors.affiliation: Department of Biology, Pennsylvania State University, University Park 16802, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Hughes
authors.forename: A L
authors.initials: AL
authors.lastname: Hughes
mesh_terms: D000818:Animals; D000940:Antigenic Variation / Q000235:genetics*; D001482:Base Composition; D001483:Base Sequence; D016368:Frameshift Mutation; D017125:Genes, Protozoan / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D010961:Plasmodium / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D008565:Membrane Proteins; D015800:Protozoan Proteins