Population biology approach to the genome diversity of Plasmodium falciparum

1.恶性疟原虫的遗传多样性由于恶性疟原虫的表面抗原基因表现出广泛的多态性，推测其多态性的快速进化。然而，很少有人知道新的多态性产生的频率。我们对太平洋西南部瓦努阿图的恶性疟原虫种群感兴趣，那里的疟疾流行病学环境适合测试新抗原多态性是否迅速演变，因为混合gentoyypes的感染很少见。我们分析了单核苷酸多态性（SNPs）和重复长度多态性在三个主要的表面抗原，msp 1，msp 2和csp，在1996年至2002年从瓦努阿图的7个岛屿的人口。我们还测序了三个微卫星位点，serca第二内含子，TA 4 O和TA 101的简单重复长度多态性。对超过一百万个碱基的分析显示，瓦努阿图的三个抗原基因中没有新的SNP。相反，重复长度多态性 关于我们 迅速旋转。对基因座之间的“连锁不平衡”分析揭示了一个频谱的人口遗传结构，这表明一些老的抗原等位基因一直坚持通过减数分裂改组的染色体后，氯喹抗性的外观在瓦努阿图。我们认为，恶性疟原虫抗原基因的SNPs在分离群体中基本上是稳定的。2.恶性疟原虫TMRCA的估计恶性疟原虫现存群体的最新共同祖先（TMRCA）时间的估计对于了解恶性疟原虫的遗传多样性至关重要。为了评估TMRCA，我们从11株恶性疟原虫和1株莱氏疟原虫（一种与恶性疟原虫密切相关的黑猩猩疟原虫）中获得了两个管家基因（肌质和内质网Ca^2+>-ATPase（serca）和乳酸脱氢酶（ldh））的全长序列。恶性疟原虫种间遗传距离为0.0672±0.0088，种内遗传距离为0.0011 ±0.0007。根据种间距离与种内距离的比值，推测恶性疟原虫的TMRCA分别为（8.30±5.40）× 10^4和（11.62±7.56）× 10^4年。少

1.Genetic diversity of PlasmodiumfalciparumSince surface antigen genes of the human malaria parasite, Plasmodium falciparum, show extensive polymorphism, a rapid evolution of their polymorphism is presumed. However, little is known about frequency of the generation of novel polymorphisms. We are interested in P.falciparum populations in Vanuatu, in the southwestern Pacific, where the malaria epidemiological settings are suitable to test whether novel antigen polymorphism evolves rapidly because infections of mixed gentoypes are rare. We analyzed single nucleotidfe polymorphisms (SNPs) and repeat-length polymorphisms in three major surface antigens, msp1,msp2 and csp, in populations from 7 islands of Vanuatu in 1996 to 2002. We also sequenced simple repeat-length polymorphisms at three microsatellite loci, serca second intron, TA4O and TA 101. Analysis of more than one million bases revealed no de novo SNPs in the three antigen genes in Vanuatu. In contrast, repeat length polymorphism e … More volved rapidly. Analysis of ‘linkage disequilibrium' between pairs of loci revealed a spectrum of population genetic structure, suggesting that some of old antigen alleles have persisted through meiotic shuffling of chromosomes after the appearance of chloroquine resistance in Vanuatu. We argue that SNPs in P.falciparum antigen genes are substantially stable in isolated populations.2.Estimation of TMRCA of Plasmodium falciparum.The estimation of the time to the most recent common ancestor (TMRCA) of the extant populations of Plasmodium falciparuim is crucial for understanding the genetic diversity of the parasite. To estimate TMRCA, we obtained full-length sequences of two housekeeping genes, sarcoplasmic and endoplasmic reticulum Ca^<2+>-ATPase (serca) and lactate dehydrogenase (ldh), from 11 isolates of P.falciparum and one isolate of P.reichenowi, a chimpanzee malaria parasite closely related to P.falciparum. Interspecific genetic distance between the two species and intraspecific genetic distance within P.falciparum were 0.0672±0.0088 and 0.00 11±0.0007, respectively. Based on the ratio of interspecific distance to intraspecific distance, TMRCA of P.falciparum was estimated to be (8.30±5.40) x 10^4 and (11.62±7.56) x 10^4 years ago, assuming the divergence time of the two parasite species to be 5 and 7 million years ago, respectively. Less