Natural selection on Plasmodium surface proteins

Mol Biochem Parasitol. 1995 Apr;71(1):99-113. doi: 10.1016/0166-6851(95)00037-2.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigenic Variation / genetics*
  • Base Composition
  • Base Sequence
  • Frameshift Mutation
  • Genes, Protozoan / genetics
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Phylogeny
  • Plasmodium / genetics*
  • Protozoan Proteins / genetics*
  • Selection, Genetic*
  • Sequence Analysis, DNA


  • Membrane Proteins
  • Protozoan Proteins