Freitas-Junior L H, Bottius E, Pirrit L A, Deitsch K W, Scheidig C, Guinet F, Nehrbass U, Wellems T E, Scherf A
Unité de Biologie des Interactions Hote-Parasite, CNRS URA 1960, Paris, France.
Nature. 2000 Oct 26;407(6807):1018-22. doi: 10.1038/35039531.
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 subtelomeric 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.
恶性疟原虫反复感染是由于该寄生虫能够发生抗原变异并逃避宿主免疫攻击。恶性疟原虫在包含细胞黏附毒力决定因素和抗原变异的基因家族中产生高水平的变异性，例如var基因。这些基因编码主要的可变寄生虫蛋白（PfEMP-1），并以互斥的方式在被恶性疟原虫感染的红细胞表面表达。在此，我们确定了一种机制，通过该机制var基因序列以远高于仅由同源交叉事件预期的频率进行重组。这些重组事件发生在异源染色体的亚端粒区域之间，这些区域在无性血液阶段寄生虫的核周边附近成簇聚集，或在有性寄生虫形式的细长细胞核一极附近呈花束状排列。我们提出，异源染色体中var基因的排列促进了基因转换并促进了抗原和黏附表型的多样性。毒力因子与特定核亚区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。
