The Role of Gene Elongation in the Evolution of Histidine Biosynthetic Genes

Abstract

Gene elongation is a molecular mechanism consisting of an in-tandem duplication of a gene and divergence and fusion of the two copies, resulting in a gene constituted by two divergent paralogous modules. The aim of this work was to evaluate the importance of gene elongation in the evolution of histidine biosynthetic genes and to propose a possible evolutionary model for some of them. Concerning the genes hisA and hisF, which code for two homologous (β/α)8-barrels, it has been proposed that the two extant genes could be the result of a cascade of gene elongation/domain shuffling events starting from an ancestor gene coding for just one (β/α) module. A gene elongation event has also been proposed for the evolution of hisB and hisD; structural analyses revealed the possibility of an early elongation event, resulting in the repetition of modules. Furthermore, it is quite possible that the gene elongations responsible for the evolution of the four proteins occurred before the earliest phylogenetic divergence. In conclusion, gene elongation events seem to have played a crucial role in the evolution of the histidine biosynthetic pathway, and they may have shaped the structures of many genes during the first steps of their evolution.

Experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis

“…According to the phylogenetic tree, an ancient γ ‐HisB‐N ‐, or β‐Proteobacterium would also be a possible donor species. Since all modern HisB‐N enzymes are N‐terminally fused to IGPDH and the respective bi‐functional genes are located within the his operon, one can assume that after the horizontal gene transfer βgmhB* was incorporated into the his operon upstream of the gene that encodes for the IGPDH, as argued previously (Brilli & Fani, 2004 ; Del Duca et al, 2020 ). The receiving γ +HisB‐N ‐Proteobacterium already possessed a βGmhB enzyme, so the selective pressure on the GmhB function of the newly transferred βgmhB* gene was likely reduced.…”

“…The route itself has been extensively studied in Escherichia coli , where eight different enzymes, including two fusion enzymes, are involved (Figure S1 ) and where the corresponding genes are organized in a tightly regulated operon (Carlomagno et al, 1988 ; Winkler & Ramos‐Montañez, 2009 ). Most of the genes and their genomic organization are conserved between phylogenetically diverse species and the corresponding enzymes possess homologous folds (Del Duca et al, 2020 ; Fani et al, 2005 ; Winkler & Ramos‐Montañez, 2009 ). However, there is one exception, namely the HolPase (Brilli & Fani, 2004 ; Kulis‐Horn et al, 2017 ).…”

The Azurin Coding Gene: Origin and Phylogenetic Distribution

“…Moreover, at least another mechanism (in addition to the well-known gene duplication followed by evolutionary divergence) can be invoked to explain the origin of extant genes from simpler ones; this molecular mechanism is referred to as gene elongation, i.e., in tandem duplication of a gene followed by the deletion of the intervening sequence and the transformation of the nonsense codon of the first gene into a sense codon, resulting in an elongated gene double the size of the ancestor gene. Concerning the latter mechanism, the analysis of the amino-acid sequence of azurin proteins from different bacteria (not shown) did not reveal the existence of internal regions sharing a degree of sequence-similarity sufficiently high to suggest that the encoding gene might be the outcome of one (or more) gene elongation event(s) [44,45]. It is also known that azurin belongs to the Cupredoxin protein family, which, in turn, includes auracyanins, amicyanins, azurins, rusticyanins, pseudoazurins, and halocyanins.…”

Application of Cloning-Free Genome Engineering to Escherichia coli

“…Lastly, in addition to the possibility of using CFGE for generating site-specific deletions of a given DNA region as demonstrated by Dohlemann et al [ 20 ], in the case of S. meliloti , A. tumefaciens , and X. campestris , the finding that two or more copies of the same amplified region can be integrated into the host chromosome might also open the way to evolutionary studies concerning the fate of in tandem duplicated genes. Indeed, it is known that gene duplication is one of the most important mechanisms driving the evolution of genes and genomes [ 41 , 42 , 43 ]. Once that a gene has duplicated, one of the two copies might accumulate mutations in such a way that the new gene (i.e., a paralog gene) acquires a metabolic ability different from the original one, thus increasing the metabolic potential of the cell.…”