Phenotype and genotype diversity in the circumsporozoite proteins of Plasmodium vivax in Thailand

Abstract

Two phenotypes of the circumsporozoite (CS) protein of the human malaria parasite Plasmodium vivax occur in Thailand, each of which has a characteristic nonamer repeat: GDRA( A D )GQPA for VK210-type and ANGAG-NQPG for VK247-type. We have sequenced the repetitive domains and flanking regions from 17 specimens collected from a small area, some of which had given ambiguous results in allele-specific hybridization or enzyme-linked immunosorbent assays (ELISA). Base substitutions occurred in non-random, limited patterns that suggest the dissemination of mutations by both unequal crossing-over and gene conversion; most substitutions were silent and phenotypic variation was relatively minor. Sequence variation and number of repeat units were much more variable in VK210-type clones than in those of VK247-type. Each VK210-type isolate with a poor ELISA response contained at least one clone with one of five residue substitutions not found in normally responsive isolates. The absence of obvious hybrid sequences between the two alleles suggests that most successful recombination may have been between sister chromatids, and the limited phenotypic variation suggests that CS antibody does not exert selective pressure on evolution.