Population biology approach to the genome diversity of Plasmodium falciparum

1.恶性疟原虫的遗传多样性由于人的恶性疟原虫表面抗原基因具有广泛的多态性，推测其多态性的快速进化。然而，对新的多态产生的频率知之甚少。我们感兴趣的是西南太平洋瓦努阿图的恶性疟原虫种群，那里的疟疾流行病学环境适合测试新的抗原多态是否由于混合正型感染罕见而迅速进化。我们分析了1996年至2002年瓦努阿图7个岛屿的人群中三种主要表面抗原MSP1、MSP2和CSP的单核苷酸多态(SNPs)和重复长度多态。我们还测定了SERCA第二内含子、TA4O和TA 101三个微卫星座位的简单重复长度多态。对100多万个碱基的分析显示，瓦努阿图的三个抗原基因中没有从头开始的SNPs。相反，重复长度多态e…更多的人迅速涌入。对两个基因座之间的连锁不平衡分析揭示了种群遗传结构的光谱，这表明在瓦努阿图出现氯喹抗性后，一些旧的抗原等位基因通过染色体的减数分裂洗牌而持续存在。我们认为恶性疟原虫抗原基因中的SNPs在隔离种群中是基本稳定的。2.恶性疟原虫TMRCA的估计。估计恶性疟原虫现存种群的最近共同祖先(TMRCA)的时间对于了解恶性疟原虫的遗传多样性至关重要。为了估计TMRCA，我们从11个恶性疟原虫分离株和一个与恶性疟原虫关系密切的黑猩猩疟原虫分离株中，获得了两个看家基因肌浆和内质网钙-ATPase(SERCA)和乳酸脱氢酶(LDH)的全长序列。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，假设两种寄生虫的分化时间分别为500万年前和700万年前，恶性疟原虫的TMRCA分别为(8.30±5.40)x 104和(11.62±7.56)x 104。较少

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