Frequent recombination events generate diversity within the multi-copy variant antigen gene families of Plasmodium falciparum
Frequent recombination events generate diversity within the multi-copy variant antigen gene families of Plasmodium falciparum
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DOI：
10.1016/j.ijpara.2008.01.010
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发表时间：
2008-08-01
影响因子：
4
通讯作者：
Deitsch, Kirk W.
中科院分区：
文献类型：
--
作者：
Frank, Matthias;Kirkman, Laura;Deitsch, Kirk W.
人类疟疾寄生虫恶性疟原虫利用抗原变异机制来避免其人类宿主的抗体反应，从而产生长期持续的感染。这个过程主要是由主要红细胞表面抗原表达的系统性变化引起的，主要红细胞表面抗原是一种寄生虫产生的蛋白质，称为PfEMPI，由恶性疟原虫基因组中超过60个var基因的库编码。var基因在单个寄生虫基因组内以及在不同寄生虫分离株之间表现出广泛的序列多样性，因此提供了在感染过程中交替展示的大量抗原决定簇。虽然最近发表了大量的工作，记录了在自然寄生虫种群中发现的var基因所表现出的极端多样性水平，但关于导致var基因序列多样化和异质性的机制却很少有人做。在从原始NF 54寄生虫分离株产生转基因株系的过程中，我们克隆并表征了一种称为E5的寄生虫株系，其与用于恶性疟原虫基因组核苷酸测序项目的寄生虫3137密切相关但不同。对E5 var基因库以及周围rif和stevor多拷贝基因家族的分析，发现了这些基因家族内频繁重组事件的例子，包括重复转座的例子，这表明重组事件在恶性疟原虫抗原编码基因内多样性的产生中发挥着重要作用。(C)2008年澳大利亚寄生虫学会由爱思唯尔有限公司出版。保留所有权利。
The human malaria parasite Plasmodium falciparum utilises a mechanism of antigenic variation to avoid the antibody response of its human host and thereby generates a long-term, persistent infection. This process predominantly results from systematic changes in expression of the primary erythrocyte surface antigen, a parasite-produced protein called PfEMPI that is encoded by a repertoire of over 60 var genes in the P. falciparunt genome. var genes exhibit extensive sequence diversity, both within a single parasite's genome as well as between different parasite isolates, and thus provide a large repertoire of antigenic determinants to be alternately displayed over the course of an infection. Whilst significant work has recently been published documenting the extreme level of diversity displayed by var genes found in natural parasite populations, little work has been done regarding the mechanisms that lead to sequence diversification and heterogeneity within var genes. In the course of producing transgenic lines from the original NF54 parasite isolate, we cloned and characterised a parasite line, termed E5, which is closely related to but distinct from 3137, the parasite used for the P. falciparum genome nucleotide sequencing project. Analysis of the E5 var gene repertoire, as well as that of the surrounding rif and stevor multi-copy gene families, identified examples of frequent recombination events within these gene families, including an example of a duplicative transposition which indicates that recombination events play a significant role in the generation of diversity within the antigen encoding genes of P. falciparum. (C) 2008 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.