Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P-falciparum
Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P-falciparum
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DOI：
10.1038/35039531
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发表时间：
2000-10-26
期刊：
影响因子：
64.8
通讯作者：
Scherf, A
中科院分区：
文献类型：
--
作者：
Freitas-Junior, LH;Bottius, E;Scherf, A
恶性疟原虫疟疾寄生虫的持续性和复发性感染是由于寄生虫具有抗原变异和逃避宿主免疫攻击的能力（1，2）。恶性疟原虫寄生虫在基因家族中产生高水平的变异性，所述基因家族包括细胞粘附和抗原变异的毒力决定簇（3-7），例如var基因。这些基因编码主要可变寄生虫蛋白（PfEMP-1），并在被恶性疟原虫感染的红细胞表面以互斥方式表达（8-12）。在这里，我们确定了一种机制，通过这种机制，var基因序列以比单独同源交换事件所预期的频率高得多的频率进行重组（13）。这些重组事件发生在异源染色体的亚端粒区域之间，其在无性血液阶段寄生虫的核周边附近的簇中或在有性寄生虫形式的细长核的一极附近的花束状配置中相关联。我们建议，在异源染色体上的var基因的对齐有利于基因转换，并促进抗原和粘附表型的多样性。毒力因子与特定的核亚区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产生影响。
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(1,2). P. falciparum parasites generate high levels of variability in gene families that comprise virulence determinants of cytoadherence and antigenic variation(3-7), 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(8-12). Here we identify a mechanism by which var gene sequences undergo recombination at frequencies much higher than those expected from homologous crossover events alone(13). 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.