Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum
Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum
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DOI：
10.1016/j.molbiopara.2007.11.004
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发表时间：
2008-03-01
影响因子：
1.5
通讯作者：
Torii, Motomi
中科院分区：
文献类型：
--
作者：
Iriko, Hideyuki;Kaneko, Osamu;Torii, Motomi
人类疟原虫恶性疟原虫的高分子质量蛋白复合物（PfRhopH）可诱导宿主保护性免疫，因此是疫苗开发的候选物。了解多态性水平和进化过程对疫苗设计和了解这种寄生虫的细胞入侵进化都很重要。在本研究中，我们对编码PfRhopH复合体蛋白的7个基因（rhoph2、rhoph3和5个rhoph1/clag基因类似物）的整个开放阅读框进行了测序。我们发现四个rhoph1/clag基因（clag2、3.1、3.2和8）具有高度多态性。这4个rhoph1/clag基因的1000 ~ 1200个氨基酸位置上主要出现氨基酸取代和缺失。clag8和9的非同义替换多于同义替换，表明正选择。采用赖氏疟原虫同源序列的McDonald-Kreitman试验也支持clag8的阳性选择。根据种间遗传距离与种内遗传距离的比值，假设恶性疟原虫和雷氏疟原虫在600万年前出现分化，估计clag2和clag8的最近共同祖先的时间分别为189万年和87万年前。除了拷贝数多态性外，还检测到3号染色体上的rhoph1/clag基因的基因转换事件，这可能在增加每个位点的多样性中起作用。我们的研究结果表明，PfRhopH1/Clag多基因家族的高度多样性是通过在相当长的一段时间内多样化的选择力来维持的。(c) 2007 Elsevier B.V.版权所有
complex of high-molecular-mass proteins (PfRhopH) of the human malaria parasite Plasmodium falciparum induces host protective immunity and therefore is a candidate for vaccine development. Understanding the level of polymorphism and the evolutionary processes is important for advancements in both vaccine design and knowledge of the evolution of cell invasion in this parasite. In the present study, we sequenced the entire open reading frames of seven genes encoding the proteins of the PfRhopH complex (rhoph2, rhoph3, and five rhoph1/clag gene paralogs). We found that four rhoph1/clag genes (clag2, 3.1, 3.2, and 8) were highly polymorphic. Amino acid substitutions and indels are predominantly clustered around amino acid positions 1000-1200 of these four rhoph1/clag genes. An excess of nonsynonymous substitutions over synonymous substitutions was detected for clag8 and 9, indicating positive selection. The McDonald-Kreitman test with a Plasmodium reichenowi orthologous sequence also supports positive selection on clag8. Based on the ratio of interspecific genetic distance to intraspecific distance, the time to the most recent common ancestor of the clag2 and 8 polymorphisms was estimated to be 1.89 and 0.87 million years ago, respectively, assuming divergence of P. falciparum and P. reichenowi 6 million years ago. In addition to a copy number polymorphism, gene conversion events were detected for the rhoph1/clag genes on chromosome 3, which likely play a role in increasing the diversity of each locus. Our results indicate that a high diversity of the PfRhopH1/Clag multigene family is maintained by diversifying selection forces over a considerably long period. (c) 2007 Elsevier B.V. All rights reserved.