The role of gene fusions in the evolution of metabolic pathways: the histidine biosynthesis case.
The role of gene fusions in the evolution of metabolic pathways: the histidine biosynthesis case.
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基因融合在代谢途径进化中的作用：组氨酸的生物合成病例。
DOI：
10.1186/1471-2148-7-s2-s4
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发表时间：
2007-08-16
影响因子：
3.4
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中科院分区：
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组氨酸的生物合成是最具特色的合成代谢途径之一。有大量的遗传和生化信息可用，包括操纵子结构、基因表达和越来越大的序列数据库。40多年来，这一途径一直是广泛研究的主题，主要是在大肠杆菌和肠道沙门氏菌中，这两种生物合成组氨酸的细节似乎是相同的。在这两个肠杆菌中，该途径是无分支的，包括一些不寻常的反应，由九个中间产物组成；他的基因排列在一个紧凑的操纵子(hisGDC[NB]HAF[IE])中，其中三个操纵子(hisNB，HISD和hisIE)编码双功能酶。我们对现有基因组中的His基因融合进行了详细的分析，以了解基因融合在塑造这一途径中的作用。对HISA结构的分析揭示了该蛋白家族的几个基因延长事件：通过组成Tim-Barrel蛋白的模块的结构叠加确定了内部复制。几个His基因的融合发生在不同的分类谱系中；HisNB起源于γ-变形杆菌，出现后被转移到弯曲杆菌(ε-变形杆菌)和属于CFB组的一些细菌。转会涉及到整个他的作曲家。HisIE基因融合在多个分类谱系中被发现，我们的结果表明，这种融合可能在不同的谱系中发生了多次。涉及HisIE和HisD基因(His4)和Hish和Hisf基因(His7)的基因融合发生在真核生物区域；后者已经转移到一些δ变形杆菌。基因复制是代谢途径起源和进化的最广为人知的机制；然而，在途径组装过程中可能还存在其他几种机制，基因融合似乎是最重要和最常见的机制之一。
Histidine biosynthesis is one of the best characterized anabolic pathways. There is a large body of genetic and biochemical information available, including operon structure, gene expression, and increasingly larger sequence databases. For over forty years this pathway has been the subject of extensive studies, mainly in Escherichia coli and Salmonella enterica, in both of which details of histidine biosynthesis appear to be identical. In these two enterobacteria the pathway is unbranched, includes a number of unusual reactions, and consists of nine intermediates; his genes are arranged in a compact operon (hisGDC [NB]HAF [IE]), with three of them (hisNB, hisD and hisIE) coding for bifunctional enzymes. We performed a detailed analysis of his gene fusions in available genomes to understand the role of gene fusions in shaping this pathway. The analysis of HisA structures revealed that several gene elongation events are at the root of this protein family: internal duplication have been identified by structural superposition of the modules composing the TIM-barrel protein. Several his gene fusions happened in distinct taxonomic lineages; hisNB originated within γ-proteobacteria and after its appearance it was transferred to Campylobacter species (ε-proteobacteria) and to some Bacteria belonging to the CFB group. The transfer involved the entire his operon. The hisIE gene fusion was found in several taxonomic lineages and our results suggest that it probably happened several times in distinct lineages. Gene fusions involving hisIE and hisD genes (HIS4) and hisH and hisF genes (HIS7) took place in the Eukarya domain; the latter has been transferred to some δ-proteobacteria. Gene duplication is the most widely known mechanism responsible for the origin and evolution of metabolic pathways; however, several other mechanisms might concur in the process of pathway assembly and gene fusion appeared to be one of the most important and common.