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首页> 外文期刊>Nature >Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum
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Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum

机译：恶性疟原虫端粒染色体簇中毒力因子基因的频繁异位重组

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摘要

Persistent and recurrent infections by Plasmodium falciparum malaria parasites result from the ability of the parasite to undergo antigenic variation and evade host immune attack. P. falciparum parasites generate high levels of variability in gene families that comprise virulence determinants of cytoadherence and antigenic variation, such as the var genes. These genes encode the major variable parasite protein (PfEMP-1), and are expressed in a mutually exclusive manner at the surface of the erythrocyte infected by P.falciparum. Here we identify a mechanism by which var gene sequences undergo recombination at frequencies much higher than those expected from homologous crossover events alone. These recombination events occur between sub-telomeric regions of heterologous chromosomes, which associate in clusters near the nuclear periphery in asexual blood-stage parasites or in bouquet-like configurations near one pole of the elongated nuclei in sexual parasite forms. We propose that the alignment of var genes in heterologous chromosomes facilitates gene conversion and promotes the diversity of antigenic and adhesive phenotypes. The association of virulence factors with a specific nuclear subcompartment may also have implications for variation during mitotic recombination in asexual blood stages.
机译：恶性疟原虫疟疾寄生虫的持续和反复感染是由于该寄生虫经历抗原变异并逃避宿主免疫攻击的能力所致。恶性疟原虫寄生虫在基因家族中产生高水平的变异性，这些变异性包括细胞粘附和抗原变异的毒力决定因素，例如var基因。这些基因编码主要的可变寄生虫蛋白（PfEMP-1），并在恶性疟原虫感染的红细胞表面以互斥的方式表达。在这里，我们确定了一种机制，通过该机制，var基因序列可以以比单独同源交换事件所期望的频率高得多的频率进行重组。这些重组事件发生在异源染色体的亚端粒区域之间，异源染色体以无性血阶段寄生虫的形式出现在核外围附近的簇中，或者以性寄生虫的形式出现在细长核的一个极点附近的花束状结构中。我们建议异种染色体中的var基因的比对促进基因转换，并促进抗原和粘附表型的多样性。毒力因子与特定核亚室的关联也可能对无性血液阶段有丝分裂重组期间的变异有影响。

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