Plasmodium falciparum: intragenic recombination and nonrandom associations between polymorphic domains of the precursor to the major merozoite surface antigens

Abstract

Extensive allelic polymorphism in the Plasmodium falciparum major merozoite antigen precursor (MSP1/PMMSA) is partly due to intragenic recombination events within a short region near the 5' end of the gene. Newly described allelic sequences from this region of the gene are compared to those previously published, revealing additional sites of intragenic recombination. Epitopes recognised by monoclonal antibodies on the protein have been assigned on the basis of correlations between serology and amino acid sequence polymorphisms among different allelic types of MSP1. Serological analyses of MSP1 from 567 wild isolates from The Gambia, Nigeria, and Brazil reveal that certain pairs of epitopes, although sited on MSP1 domains separated by known sites of intragenic recombination, are highly significantly associated on parasites in endemic populations. Most associations are similar in the three countries. These associations are discussed with respect to the intragenic recombination hypothesis.