Sequence diversity and linkage disequilibrium within the merozoite surfaceprotein-1 (Msp-1) locus of Plasmodium falciparum: A longitudinal study in Brazil

The merozoite surface protein-1 (MSP-1) is a major vaccine candidate for th e asexual blood stage of malaria. We examined both the extent of sequence d iversity in block 17, the 3' end of Msp-1 gene coding for a 19-kDa polypept ide (MSP-j(19)) putatively involved in red blood cell binding, and the patt erns of linkage disequilibrium between polymorphic sires throughout the Msp -1 locus. The parasite population sample consisted of Plasmodium falciparum isolates collected between 1985 and 1998 in rondonia. an area of hypoendem ic malaria transmission in the southwestern Brazilian Amazon. Results were summarized as follows. (1) Seven block-17 sequence variants or haplotypes w ere found among 130 isolates, including two new haplotypes (novel combinati ons of previously reported amino acid replacements), here named Brazil-1 (E -TSR-F) and Brazil-2 (Q-TSR-F). (2) As previously shown for other Msp-1 pol ymorphisms, frequencies of block-17 haplotypes displayed significant tempor al variation. (3) Extensive linkage disequilibrium was demonstrated between neighboring dimorphic sires within block 17. as well as between polymorphi sms at the 5' and 3' ends of Msp-1 (map distance range: 3.83-4.99 kb). (4) The overall patterns of linkage disequilibrium within Msp-1 remained stable over a period of nearly one decade, and examples of possible 'epidemic' ex pansion of parasites carrying particular Msp-1 alleles were found in the 19 80s and 1990s. These results are discussed in relation to the population bi ology of P. falciparum and the development of malaria vaccines based on MSP -1.