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恶性疟原虫的变异基因位于大多数染色体的亚端粒区域。

The var genes of Plasmodium falciparum are located in the subtelomeric region of most chromosomes.

作者信息

Rubio J P, Thompson J K, Cowman A F

机构信息

The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Melbourne, Victoria, Australia 3050.

出版信息

EMBO J. 1996 Aug 1;15(15):4069-77.

Abstract

PfEMP1, a Plasmodium falciparum-encoded protein on the surface of infected erythrocytes is a ligand that mediates binding to receptors on endothelial cells. The PfEMP1 protein, which is encoded by the large var gene family, shows antigenic variation and changes in binding phenotype associated with alterations in antigenicity. We have constructed a yeast artificial chromosome contig of chromosome 12 from P. falciparum and show that var genes are arranged in four clusters; two lie amongst repetitive subtelomeric sequences and two occur in the more conserved central region. Analysis of parasite chromosomes by pulsed field gel electrophoresis (PFGE) demonstrates that most contain var genes and two-dimensional PFGE has shown that var genes are located at chromosome ends interspersed amongst repetitive sequences present in the subtelomeric complex. Analysis of a var gene located in the subtelomeric region of chromosome 12 has shown that it has close homologues at the opposite end of the chromosome and in the subtelomeric region of two other chromosomes. This suggests that recombination between heterologous chromosomes has occurred in the subtelomeric regions of these chromosomes. The subtelomeric location of var genes dispersed amongst repetitive sequences has important implications for generation of antigenic variants and novel cytoadherent specificities of this protein.

摘要

恶性疟原虫红细胞膜蛋白1(PfEMP1)是一种由恶性疟原虫编码、位于受感染红细胞表面的蛋白质,是一种介导与内皮细胞表面受体结合的配体。PfEMP1蛋白由庞大的var基因家族编码,具有抗原变异特性,其结合表型的变化与抗原性改变相关。我们构建了恶性疟原虫1号染色体的酵母人工染色体重叠群,结果显示var基因排列成四个簇;其中两个位于重复的亚端粒序列中,另外两个位于较为保守的中央区域。通过脉冲场凝胶电泳(PFGE)分析疟原虫染色体表明,大多数染色体含有var基因,二维PFGE显示var基因位于染色体末端,散布于亚端粒复合体中的重复序列之间。对位于12号染色体亚端粒区域的一个var基因进行分析发现,它在该染色体的另一端以及另外两条染色体的亚端粒区域有密切的同源物。这表明在这些染色体的亚端粒区域发生了异源染色体之间的重组。var基因散布于重复序列中的亚端粒定位对于该蛋白抗原变体的产生以及新的细胞黏附特异性具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6255/452127/4c6e2a886ace/emboj00015-0306-a.jpg

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