Adaptive Evolution of RH5 in Ape Plasmodium species of the Laverania Subgenus.
Adaptive Evolution of RH5 in Ape Plasmodium species of the Laverania Subgenus.
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Laverania子属的猿类疟原虫种类RH5的自适应演变。
DOI：
10.1128/mbio.02237-17
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发表时间：
2018-01-23
期刊：
影响因子：
6.4
通讯作者：
Sharp PM
中科院分区：
文献类型：
--
作者：
Plenderleith LJ;Liu W;MacLean OA;Li Y;Loy DE;Sundararaman SA;Bibollet-Ruche F;Learn GH;Hahn BH;Sharp PM
恶性疟原虫是人类疟疾发病和死亡的主要原因，已被证明是在感染野生黑猩猩（类人猿）和西部大猩猩（大猩猩）的六种宿主特异性寄生虫（狐猴亚属）中的一种跨物种传播后出现的。寄生虫编码的配体RH5与宿主蛋白basigin的结合是红细胞入侵所必需的，并且与宿主特异性有关。最近的一项研究声称发现了RH5中两个氨基酸的变化，这些变化“推动了宿主的转变，导致恶性疟原虫作为人类病原体的出现”。然而，当时可用的猿类资料，只包括一个与黑猩猩有远亲关系的寄生虫序列，不足以证明任何这样的结论。在这里，我们利用所有6种猿类寄生虫的序列研究了Laverania Rh5基因的进化。在整个狐猴系统发育中搜索基因范围的偶发性选择，我们发现8个密码子处于正选择状态，其中3个密码子对应于恶性疟原虫RH5与人类盆地之间形成氢键的接触残基。其中一个位点（残留197）在猿类向人类传播后发生了变化，从而产生了恶性疟原虫，这表明大猩猩寄生虫可能在适应人类宿主方面发挥了作用。我们还发现证据表明，恶性疟原虫的核苷酸多态性模式并非狐蝠属物种的典型特征，可能反映了人类寄生虫的近期人口统计学历史。一些密切相关的，宿主特异性疟疾寄生虫感染野生黑猩猩和大猩猩最近被描述。人类疟疾最重要的病因——恶性疟原虫，现在已知是由一种大猩猩寄生虫的跨物种传播造成的。克服寄生虫配体RH5与其宿主细胞受体basigin之间的物种特异性相互作用，可能是人类寄生虫起源的重要一步。我们研究了Rh5基因的进化，并在已知与人类盆地形成联系的位点发现了猿寄生物种多样化过程中适应性变化的证据。其中一个变化发生在恶性疟原虫的起源，这意味着它是对人类宿主的重要适应。
Plasmodium falciparum, the major cause of malaria morbidity and mortality in humans, has been shown to have emerged after cross-species transmission of one of six host-specific parasites (subgenus Laverania) infecting wild chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla). Binding of the parasite-encoded ligand RH5 to the host protein basigin is essential for erythrocyte invasion and has been implicated in host specificity. A recent study claimed to have found two amino acid changes in RH5 that “drove the host shift leading to the emergence of P. falciparum as a human pathogen.” However, the ape Laverania data available at that time, which included only a single distantly related chimpanzee parasite sequence, were inadequate to justify any such conclusion. Here, we have investigated Laverania Rh5 gene evolution using sequences from all six ape parasite species. Searching for gene-wide episodic selection across the entire Laverania phylogeny, we found eight codons to be under positive selection, including three that correspond to contact residues known to form hydrogen bonds between P. falciparum RH5 and human basigin. One of these sites (residue 197) has changed subsequent to the transmission from apes to humans that gave rise to P. falciparum, suggesting a possible role in the adaptation of the gorilla parasite to the human host. We also found evidence that the patterns of nucleotide polymorphisms in P. falciparum are not typical of Laverania species and likely reflect the recent demographic history of the human parasite. A number of closely related, host-specific malaria parasites infecting wild chimpanzees and gorillas have recently been described. The most important cause of human malaria, Plasmodium falciparum, is now known to have resulted from a cross-species transmission of one of the gorilla parasites. Overcoming species-specific interactions between a parasite ligand, RH5, and its receptor on host cells, basigin, was likely an important step in the origin of the human parasite. We have investigated the evolution of the Rh5 gene and found evidence of adaptive changes during the diversification of the ape parasite species at sites that are known to form bonds with human basigin. One of these changes occurred at the origin of P. falciparum, implicating it as an important adaptation to the human host.