Structural basis for segmental gene conversion in generation of Anaplasma marginale outer membrane protein variants
Structural basis for segmental gene conversion in generation of Anaplasma marginale outer membrane protein variants
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DOI：
10.1111/j.1365-2958.2005.04670.x
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发表时间：
2005-07-01
影响因子：
3.6
通讯作者：
Palmer, GH
中科院分区：
文献类型：
--
作者：
Futse, JE;Brayton, KA;Palmer, GH
无形体属的细菌病原体通过将染色体假基因转化为单表达位点来产生表面被膜变体。这些假基因编码独特的表面暴露的高变区，其侧翼是保守结构域，其与表达位点侧翼结构域相同。此外，边缘无形体通过将源自假基因的寡核苷酸区段重组到现有表达位点拷贝中来产生变体，导致变体多样性的组合增加。利用A.边缘基因组序列为了追踪重组到msp 2表达位点中的序列的起源，我们证明了在感染期间表达的msp 2的复杂性增加，反映了从给定假基因的完整高变区的重组到具有源自不同假基因的高变区的区段的复杂嵌合体的转变。检查1183个片段变化的变体的完整集合显示，99%可以通过保守的侧翼结构域中发生的重组位点之一和高变区中的另一个来解释。因此，我们提出了一个“锚定”模型的节段基因转换，其中保守的侧翼序列紧密对齐和锚的表达位点序列的假基因。与重组位点相关的是缺失、插入和取代;然而，这些对变体生成的贡献相对较小，因为这些发生在不到2%的变体中。重要的是，锚定模型，它可以解释更多的变异比严格的片段序列同一性机制，是一致的msp 2变异的数量预测和经验确定在持续感染。
Bacterial pathogens in the genus Anaplasma generate surface coat variants by gene conversion of chromosomal pseudogenes into single-expression sites. These pseudogenes encode unique surface-exposed hypervariable regions flanked by conserved domains, which are identical to the expression site flanking domains. In addition, Anaplasma marginale generates variants by recombination of oligonucleotide segments derived from the pseudogenes into the existing expression site copy, resulting in a combinatorial increase in variant diversity. Using the A. marginale genome sequence to track the origin of sequences recombined into the msp2 expression site, we demonstrated that the complexity of the expressed msp2 increases during infection, reflecting a shift from recombination of the complete hypervariable region of a given pseudogene to complex mosaics with segments derived from hypervariable regions of different pseudogenes. Examination of the complete set of 1183 variants with segmental changes revealed that 99% could be explained by one of the recombination sites occurring in the conserved flanking domains and the other within the hypervariable region. Consequently, we propose an 'anchoring' model for segmental gene conversion whereby the conserved flanking sequences tightly align and anchor the expression site sequence to the pseudogene. Associated with the recombination sites were deletions, insertions and substitutions; however, these are a relatively minor contribution to variant generation as these occurred in less than 2% of the variants. Importantly, the anchoring model, which can account for more variants than a strict segmental sequence identity mechanism, is consistent with the number of msp2 variants predicted and empirically identified during persistent infection.