Molecular approaches to the genetic diversity of malaria parasites

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The genetic diversity of surface antigens of malaria parasites was studied on field isolates from geographic endemic areas. Analysis of about 500 isolates by PCR and DNA sequencing revealed the followings.1. Polymorphism of the merozoite surface antigen gene (PfMsp-1) of P. falciparum: Linkage disequilibrium between polymorphic sites in the 5'-region (blocks 2-6) and 3'-region (block 17) of PfMsp-1 in parasite population from Thailand, Vietnam and Brazil The strength of this linkage disequilibrium correlated with the intensity of transmission of malaria. It is suggested that both selection and genetic drift are involved in this linkage disequilibrium. The diversity of PfMsp-1 was very limited in Vanuatu with very strong linkage disequilibrium between the 5'- and 3' - polymorphic sites. Extremely low rate of mixed clone infections in Vanuatu suggests that the rate of recombination in PfMsp-1 depends on not only the intensity of transmission but the frequency of mixed infection and the number of alleles present in an endemic area.2. Polymorphism of the merozoite surface antigen gene (PvMsp-1) of P. vivax: In order to examine in-depth structural organization of PvMsp-1 , complete nucleotide sequencing of the gene of 40 isolates obtained from geographic areas was done. Sequence alignment revealed that (i) PvMsp-1 consist of 7 variable blocks interspersed with 8 conserved blocks, (ii) variation is primarily dimorphic, and (iii) potential recombination sites occur throughout the gene. These results suggest that allelic recombination is the major mechanism for generating the diversity in PvMsp-1.