Abstract
BackgroundHistidine 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.ResultsThe 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.ConclusionGene 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.
Highlights
Histidine biosynthesis is one of the best characterized anabolic pathways
Several his gene fusions happened in distinct taxonomic lineages; hisNB originated within γproteobacteria and after its appearance it was transferred to Campylobacter species and to some Bacteria belonging to the CFB group
The hisIE gene fusion was found in several taxonomic lineages and our results suggest that it probably happened several times in distinct lineages
Summary
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. There is a large body of genetic and biochemical information available, mainly for Escherichia coli and Salmonella enterica, including operon structure, gene expression, and growing sequence data [1] In these two enterobacteria, the pathway is the same, 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 (Figure 1) [2,3]. The connection to purine biosynthesis results from an enzymatic step catalyzed by imidazole glycerol phosphate (IGP) synthase, a heterodimeric protein composed by one subunit each of the hisH and hisF products [2] This heterodimeric enzyme catalyzes the transformation of N'-(5'-phosphoribosyl)-formimino-5aminoimidazol-4-carboxamide ribonucleotide (PRFAR) into 5'-(5-aminoimidazole-4-carboxamide) ribonucleotide (AICAR), which is recycled into the de novo purine biosynthetic pathway, and IGP, which leads to histidine. The chemical syntheses of histidine [4], prebiotic analogues of histidine [5], and of histidyl-histidine under primitive conditions has been reported [6], as well as the role of the latter in the enhancement of some possible prebiotic oligomerization de novo synthesisof purines
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