Molecular evolution of antigen polymoiphism of modem malaria parasite populations

1. 感染多重性（multiplicity of infection， MOI）的地理差异比较不同地理区域恶性疟原虫人群的感染多重性（multiplicity of infection， MOI）。基于pcr的mspl- 5’单倍型测定的MOI在非洲较高，而在美拉尼西亚，MOI与疟疾传播强度之间没有明显的关联。结果表明，菌株特异性疟疾保护性免疫的获得不仅与疟疾传播强度有关，而且与当地流行的基因型数量和moi有关。为了研究间日疟原虫mspl多态性的进化历史，构建了间日疟原虫及其相关猴疟原虫mspl的系统发育树。间日疟原虫mspl等位基因全部集中在间日疟原虫谱系中，而不分布于其他种中。同样地，所有的cynomolgi mspl等位基因都聚集在cynomolgi谱系中。这表明间日疟原虫msp1多态性的起源相对较晚。我们在间日疟原虫谱系中观察到阳性选择，而在食蟹疟原虫谱系中没有。这一研究表明，mspl的进化历史在不同寄生虫谱系之间存在很大差异。为了推测疟原虫属的SSUrRNA系统发育，我们从8个类人猿疟原虫种中获得了编码细胞SSUrRNA （a型和s型）旁同源拷贝的基因序列。这些序列的最大似然分析，连同数据库中现有的所有细胞- ssurrna序列，清楚地显示了在无根疟原虫树中有四个独立的分支：类人猿疟原虫+间日疟原虫分支，啮齿动物疟原虫分支（P. berghei/P.）。包括疟疾疟原虫、恶性疟原虫、疟原虫、鸟类和爬行动物疟原虫在内的一个大进化支，以及卵形进化支。

1. Geographic variation in multiplicity of infectionMultiplicity of infection (MOI) was compared among P falciparum populations from diverse geographic areas. MOI as measured by PCR-based mspl- 5' haplotyping was high in Africa, whereas there was no discernible association between MOI and the intensity of malaria transmission in Melanesia. Results suggest that the acquisition of strain specific protective immunity against malaria is associated with not only the intensity of malaria transmission but also the number of genotypes prevalent in local areas and MOI.2. Origin of and natural selection in mspl polymorphism of P. vivaxTo investigate the evolutionary history of mspl polymorphism in P vivax, phylogenetic trees of mspl from P. vivax and related monkey malaria parasite species was constructed. All P vivax mspl alleles cluster in the P vivax lineage and are not distributed among other species. Similarly, all P cynomolgi mspl alleles cluster in the P cynomolgi lineage. This suggests that the origin of P. vivax mspl polymorphism is relatively recent. We observed positive selection_in the P vivax lineage but not in P cynomolgi. This study shows that the evolutionary history of mspl differs greatly among parasite lineages.3. Phylogeny of the cytosolic SSUrRNA of Plasmodium spp.To infer the SSUrRNA phylogeny of the genus Plasmodium, sequences of genes encoding paralogous copies of the cyto-SSUrRNA, A-type-like and S-type-like genes, from eight simian Plasmodium species were obtained. The maximum likelihood analyses of these sequences, together with all cyto-SSUrRNA sequences currently available in the database, clearly demonstrated four independent clades in the unrooted Plasmodium tree: a simian Plasmodium + P vivax clade, a rodent Plasmodium clade (P. berghei/P. yoelii), a large clade including P malariae, P. falciparum, P reichnowi, and avian and reptilian Plasmodium species, and a P ovale clade.