Ward C P, Clottey G T, Dorris M, Ji D D, Arnot D E
Institute of Cell, Animal and Population Biology, Division of Biology, University of Edinburgh, Scotland, UK.
Mol Biochem Parasitol. 1999 Jul 30;102(1):167-77. doi: 10.1016/s0166-6851(99)00106-1.
The var genes of Plasmodium falciparum encode a family of parasite erythrocyte surface antigens, the PfEMP-1 proteins, which function as adhesion ligands for host endothelial and erythrocyte receptors. PfEMP-1 is extremely polymorphic although the extent of this variation in naturally transmitted parasite populations is unclear. We have identified 56 different sequences from the Duffy binding-like (DBL-1) domain of var genes amplified from six different P. falciparum clones isolated from patient infections in a Sudanese village in October-November 1989. These clones have been compared with 25 PfEMP-1 sequences expressed from different var gene loci by the 3D7A clone and 48 PfEMP-1 sequences from different isolates in endemic areas such as Kenya, Brazil, Gambia, Vietnam and Vanuatu to analyse diversity in clonal, local and 'global' P. falciparum populations. Evidence that certain conserved sequences recur in clones from one Sudanese village and in isolates from all over the world suggests that var gene diversity is the result of recombinational reshuffling of a subset of conserved, presumably ancestral sequences. Recurrence of particular var sequence blocks thus leads to 'overlaps' in the PfEMP-1 sequence repertoire of different P. falciparum clones.
恶性疟原虫的var基因编码一类寄生虫红细胞表面抗原，即PfEMP-1蛋白，其作为宿主内皮细胞和红细胞受体的黏附配体发挥作用。尽管在自然传播的寄生虫群体中这种变异的程度尚不清楚，但PfEMP-1具有极高的多态性。我们从1989年10月至11月在苏丹一个村庄从患者感染中分离出的6个不同恶性疟原虫克隆中扩增出var基因的达菲结合样（DBL-1）结构域，鉴定出了56个不同序列。这些克隆已与3D7A克隆从不同var基因座表达的25个PfEMP-1序列以及来自肯尼亚、巴西、冈比亚、越南和瓦努阿图等流行地区不同分离株的48个PfEMP-1序列进行比较，以分析克隆、本地和“全球”恶性疟原虫群体中的多样性。来自苏丹一个村庄的克隆以及来自世界各地分离株中某些保守序列反复出现的证据表明，var基因多样性是保守的、可能是祖先序列的一个子集通过重组重排的结果。特定var序列块的反复出现因此导致不同恶性疟原虫克隆的PfEMP-1序列库出现“重叠”。
