Maier Alexander G, Duraisingh Manoj T, Reeder John C, Patel Sheral S, Kazura James W, Zimmerman Peter A, Cowman Alan F
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Nat Med. 2003 Jan;9(1):87-92. doi: 10.1038/nm807. Epub 2002 Dec 9.
Geographic overlap between malaria and the occurrence of mutant hemoglobin and erythrocyte surface proteins has indicated that polymorphisms in human genes have been selected by severe malaria. Deletion of exon 3 in the glycophorin C gene (called GYPCDeltaex3 here) has been found in Melanesians; this alteration changes the serologic phenotype of the Gerbich (Ge) blood group system, resulting in Ge negativity. The GYPCDeltaex3 allele reaches a high frequency (46.5%) in coastal areas of Papua New Guinea where malaria is hyperendemic. The Plasmodium falciparum erythrocyte-binding antigen 140 (EBA140, also known as BAEBL) binds with high affinity to the surface of human erythrocytes. Here we show that the receptor for EBA140 is glycophorin C (GYPC) and that this interaction mediates a principal P. falciparum invasion pathway into human erythrocytes. EBA140 does not bind to GYPC in Ge-negative erythrocytes, nor can P. falciparum invade such cells using this invasion pathway. This provides compelling evidence that Ge negativity has arisen in Melanesian populations through natural selection by severe malaria.
疟疾与突变血红蛋白及红细胞表面蛋白出现的地理重叠表明，人类基因中的多态性是由严重疟疾选择的。在美拉尼西亚人身上发现了血型糖蛋白C基因中外显子3的缺失（此处称为GYPCDeltaex3）；这种改变改变了Gerbich（Ge）血型系统的血清学表型，导致Ge阴性。在疟疾高度流行的巴布亚新几内亚沿海地区，GYPCDeltaex3等位基因的频率很高（46.5%）。恶性疟原虫红细胞结合抗原140（EBA140，也称为BAEBL）与人类红细胞表面具有高亲和力结合。我们在此表明，EBA140的受体是血型糖蛋白C（GYPC），并且这种相互作用介导了恶性疟原虫进入人类红细胞的主要入侵途径。EBA140不会与Ge阴性红细胞中的GYPC结合，恶性疟原虫也不能利用这种入侵途径侵入此类细胞。这提供了令人信服的证据，表明Ge阴性在美拉尼西亚人群中是通过严重疟疾的自然选择而出现的。
