Molecular approaches to the genetic diversity of malaria parasites

用地理流行区的野外分离株研究了疟疾寄生虫表面抗原的遗传多样性。对约500株分离物进行了聚合酶链式反应和DNA测序分析，结果如下。恶性疟原虫裂殖子表面抗原基因(PfMsp-1)的多态性：在泰国、越南和巴西的寄生虫群体中，PfMsp-1的5‘区(第2-6区)和3’区(第17区)的多态位点之间存在连锁不平衡。这种连锁不平衡的程度与疟疾传播的强度有关。推测该连锁不平衡与选择和遗传漂移有关。在瓦努阿图，PfMsp-1的多样性非常有限，5‘和3’多态位点之间存在很强的连锁不平衡。瓦努阿图极低的混合克隆感染率表明，PfMsp-1的重组率不仅取决于传播强度，而且取决于混合感染的频率和流行地区存在的等位基因数量。间日疟原虫裂殖子表面抗原基因(PvMsp-1)的多态性研究：为了解间日疟原虫裂殖子表面抗原基因(PvMsp-1)的结构组成，对从不同地区分离到的40株裂殖子表面抗原基因进行了核苷酸全序列测定。序列比对表明：(I)PvMsp-1由7个可变区和8个保守区组成，(Ii)变异主要是二态的，(Iii)潜在的重组位点存在于整个基因中。这些结果表明，等位基因重组是产生PvMsp-1多样性的主要机制。

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.