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首页> 外文期刊>Molecular Microbiology >Plasmodium falciparum antigenic variation. Mapping mosaic var gene sequences onto a network of shared, highly polymorphic sequence blocks
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Plasmodium falciparum antigenic variation. Mapping mosaic var gene sequences onto a network of shared, highly polymorphic sequence blocks

机译：恶性疟原虫的抗原变异。将镶嵌var基因序列映射到共享的高度多态序列块的网络上

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摘要

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a potentially important family of immune targets, encoded by an extremely diverse gene family called var. Understanding of the genetic organization of var genes is hampered by sequence mosaicism that results from a long history of non-homologous recombination. Here we have used software designed to analyse social networks to visualize the relationships between large collections of short var sequences tags sampled from clinical parasite isolates. In this approach, two sequences are connected if they share one or more highly polymorphic sequence blocks. The results show that the majority of analysed sequences including several var-like sequences from the chimpanzee parasite Plasmodium reichenowi can be either directly or indirectly linked together in a single unbroken network. However, the network is highly structured and contains putative subgroups of recombining sequences. The major subgroup contains the previously described group A var genes, previously proposed to be genetically distinct. Another subgroup contains sequences found to be associated with rosetting, a parasite virulence phenotype. The mosaic structure of the sequences and their division into subgroups may reflect the conflicting problems of maximizing antigenic diversity and minimizing epitope sharing between variants while maintaining their host cell binding functions.
机译：恶性疟原虫红细胞膜蛋白1（PfEMP1）是潜在的重要免疫靶标家族，由称为var的极为多样的基因家族编码。对var基因的遗传组织的理解受到了序列镶嵌的阻碍，而序列镶嵌是源于非同源重组的悠久历史。在这里，我们使用了旨在分析社交网络的软件，以可视化从临床寄生虫分离株中采样的短var序列标签的大量集合之间的关系。在这种方法中，如果两个序列共享一个或多个高度多态的序列块，则它们将相连。结果表明，大多数分析序列，包括来自黑猩猩寄生虫疟原虫的几个var-like序列，都可以在一个完整的网络中直接或间接连接在一起。但是，该网络具有高度的结构，并包含重组序列的假定子组。主要亚组包含先前描述的A组var基因，先前提出具有遗传差异。另一个亚组包含发现与玫瑰花结（一种寄生虫毒力表型）相关的序列。序列的镶嵌结构及其划分为亚组可能反映了在保持它们的宿主细胞结合功能的同时，使抗原多样性最大化和变体之间的表位共享最小化的矛盾问题。

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