Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1)

Abstract

Immunization with the first identified Plasmodium falciparum merozoite surface protein (MSP-1) protected monkeys from an otherwise fatal infection. The question of whether the high degree of diversity in MSP-1 among parasite clones will be an impediment to its development as a vaccine candidate needs to be resolved. We have aligned all published sequences, identifying errors, resequencing a portion of one parasite clone, and identifying probable duplicate sequences of four pairs of parasite clones. The sequences are displayed in a fashion that facilitates the study of variation and its potentially diverse origins. The original dimorphic sequences described by Tanabe et al. have been modified to include only common sequences throughout the entire gene. The extension of the dimorphic region to the 5' end of block 3 brings into question the involvement of intragenic crossover as the major mechanism generating allelic diversity. Additional diversity developed from point mutations and recombination in certain regions of the gene. The regions of variability and conservation should serve as a data base for planning vaccine trials.