Allelic recombination and linkage disequilibrium within Msp-1 of Plasmodium falciparum, the malignant human malaria parasite

The C-terminal, cysteine-rich 19 kDa domain of merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a target of the host's humoral immunity and thus a malaria vaccine candidate. Although variation in the 19 kDa dom ain is limited among parasite isolates, tertiary structure-dependent intram olecular associations between the 19 kDa domain and other parts of MSP-1 ar e suggested to be involved in immune evasion by allowing competitive bindin g of protective and non-protective antibodies directed to their epitopes, w hich are conformationally in close proximity but separated at the primary s tructure. Since allelic recombination can account for the major variability of the Msp-1 gene, we examined whether linkage disequilibrium occurs betwe en polymorphic loci in the 5'- and the 3'-region, the latter encoding the 1 9 kDa domain. From 184 Thai held isolates, we selected 69 isolates with a s ingle allelic type in six variable blocks of Msp-1 as determined by PCR-bas ed allelic typing. All the isolates showed no evidence of recombination in blocks 6 to 16, whereas recombination was apparent in blocks 2 to 6. Sequen cing of the 3'-region revealed two potential recombination sites in block 1 7. Strong linkage disequilibrium was seen between polymorphic loci in the 5 '- and 3'-regions. The strength of this disequilibrium did not correlate wi th distance between loci. We discuss the possible role of epistatic selecti on on particular association types (haplotypes) of Msp-1. (C) 1999 Elsevier Science B.V. All rights reserved.