Data from: Positive selection underlies the species-specific binding of P. falciparum RH5 to human basigin

Plasmodium falciparum, the causative agent of the deadliest form of malaria, is a member of the Laverania subgenus, which includes ape-infecting parasites. P. falciparum is thought to have originated in gorillas, although infection is now restricted to humans. Laverania parasites display remarkable host-specificity, which is partially mediated by the interaction between parasite ligands and host receptors. We analyse the evolution of BSG (basigin) and GYPA (glycophorin A) in primates/hominins, as well as of their Plasmodium-encoded ligands, PfRH5 and PfEBA175. We show that, in primates, positive selection targeted two sites in BSG (F27 and H102), both involved in PfRH5 binding. A population genetics–phylogenetics approach detected the strongest selection for the gorilla lineage: one of the positively selected sites (K191) is a major determinant of PfRH5 binding affinity. Analysis of RH5 genes indicated episodic selection on the P. falciparum branch; the positively selected W447 site is known to stabilize the interaction with human basigin. Conversely, we detect no selection in the receptor-binding region of EBA175 in the P. falciparum lineage. Its host receptor, GYPA, shows evidence of positive selection in all hominid lineages; selected codons include glycosylation sites that modulate PfEBA175 binding affinity. Data herein provide an evolutionary explanation for species-specific binding of the PfRH5-BSG ligand–receptor pair and support the hypothesis that positive selection at these genes drove the host shift leading to the emergence of P. falciparum as a human pathogen.恶性疟原虫（Plasmodium falciparum）是引发最致命型疟疾的病原体，隶属于Laverania亚属（Laverania subgenus）的一员，该亚属包含感染猿类的寄生虫。恶性疟原虫被认为起源于大猩猩，尽管目前其感染仅局限于人类。Laverania亚属寄生虫展现出显著的宿主特异性，这一特性部分由寄生虫配体与宿主受体的相互作用所介导。本研究分析了灵长类/人亚族动物中BSG（basigin）和血型糖蛋白A（GYPA）的进化历程，同时也分析了疟原虫编码的配体PfRH5与PfEBA175的进化情况。研究显示，在灵长类动物中，正选择（positive selection）靶向了BSG中的两个位点（F27与H102），这两个位点均参与PfRH5的结合过程。采用群体遗传学-系统发育学（population genetics–phylogenetics）方法，检测到大猩猩支系受到最强的选择压力：其中一个正选择位点（K191）是决定PfRH5结合亲和力的关键决定因素。对RH5基因的分析显示，恶性疟原虫支系上存在间断性选择（episodic selection）；经证实，正选择位点W447可稳定其与人类basigin的相互作用。与之相反，本研究未在恶性疟原虫支系的EBA175受体结合区域检测到选择压力。其宿主受体血型糖蛋白A（GYPA）在所有人科支系中均呈现正选择信号；受选择的密码子包含可调节PfEBA175结合亲和力的糖基化位点。本研究数据为PfRH5-BSG配体-受体对的物种特异性结合提供了进化层面的解释，并支持如下假说：上述基因的正选择推动了宿主转换（host shift）事件，最终促使恶性疟原虫成为人类致病原虫。