Ape parasite origins of human malaria virulence genes.
Ape parasite origins of human malaria virulence genes.
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DOI：
10.1038/ncomms9368
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发表时间：
2015-10-12
影响因子：
16.6
通讯作者：
Buckee CO
中科院分区：
文献类型：
--
作者：
Larremore DB;Sundararaman SA;Liu W;Proto WR;Clauset A;Loy DE;Speede S;Plenderleith LJ;Sharp PM;Hahn BH;Rayner JC;Buckee CO
由var基因家族编码的抗原是人类恶性疟原虫的主要毒力因子，表现出巨大的株内和株间多样性。在这里，我们使用网络分析表明，var架构和镶嵌在多个层次上保守的Laverania亚属，根据var样序列从8个单一物种和3个多物种疟原虫感染的野生动物或避难所非洲猿。使用选择的全基因组扩增，我们还发现了多域变异结构和同线性的证据，在疟原虫gaboni，一个类人猿Laverania物种最远的相关恶性疟原虫，以及一类新的达菲结合样结构域。这些研究结果表明，模块化的遗传结构和序列多样性的var介导的宿主-寄生虫相互作用之前的Laverania亚属的辐射，早在恶性疟原虫的出现。 var基因编码的抗原是恶性疟原虫的主要毒力因子。在这里，Larremore等人在感染非洲猿类的远亲疟原虫物种中发现了var样基因，表明这些基因在数百万年前就已经存在于猿类寄生虫的祖先中。
Antigens encoded by the var gene family are major virulence factors of the human malaria parasite Plasmodium falciparum, exhibiting enormous intra- and interstrain diversity. Here we use network analysis to show that var architecture and mosaicism are conserved at multiple levels across the Laverania subgenus, based on var-like sequences from eight single-species and three multi-species Plasmodium infections of wild-living or sanctuary African apes. Using select whole-genome amplification, we also find evidence of multi-domain var structure and synteny in Plasmodium gaboni, one of the ape Laverania species most distantly related to P. falciparum, as well as a new class of Duffy-binding-like domains. These findings indicate that the modular genetic architecture and sequence diversity underlying var-mediated host-parasite interactions evolved before the radiation of the Laverania subgenus, long before the emergence of P. falciparum. Antigens encoded by var genes are major virulence factors of the human malaria parasite Plasmodium falciparum. Here, Larremore et al. identify var-like genes in distantly related Plasmodium species infecting African apes, indicating that these genes already existed in an ancestral ape parasite many millions of years ago.