Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family
Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family
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DOI：
10.1046/j.1365-2958.2003.03814.x
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发表时间：
2003-12-01
影响因子：
3.6
通讯作者：
Smith, JD
中科院分区：
文献类型：
--
作者：
Kraemer, SM;Smith, JD
var基因家族编码恶性疟原虫红细胞膜1 （PfEMP1）蛋白，该蛋白作为毒力因子负责感染红细胞的抗原变异和细胞粘附。这些蛋白质协调被感染的红细胞从血液循环中隔离，并导致恶性疟原虫疟疾感染的黏附并发症。在这项研究中，我们分析了var基因的遗传组织和菌株结构，并提供了三个独立进化群体的证据，这些群体在亚端粒和中央染色体位置之间部分地存在功能分化和差异。我们的分析表明，重组等级限制了群体之间的重组，并可能解释为什么一些var基因在寄生虫菌株之间异常保守。这种重组层次，加上结合和免疫选择，形成了变异抗原库，并对与疟疾发病直接相关的PfEMP1蛋白家族具有结构、功能和进化影响。
The var gene family encodes Plasmodium falciparum erythrocyte membrane 1 (PfEMP1) proteins that act as virulence factors responsible for both antigenic variation and cytoadherence of infected erythrocytes. These proteins orchestrate infected erythrocyte sequestration from blood circulation and contribute to adhesion-based complications of P. falciparum malaria infections. For this study, we analysed the genetic organization and strain structure of var genes and present evidence for three separately evolving groups that have, in part, functionally diverged and differ between subtelomeric and central chromosomal locations. Our analyses suggest that a recombination hierarchy limits reassortment between groups and may explain why some var genes are unusually conserved between parasite strains. This recombination hierarchy, coupled with binding and immune selection, shapes the variant antigen repertoire and has structural, functional and evolutionary consequences for the PfEMP1 protein family that are directly relevant to malaria pathogenesis.