Enzyme evolution beyond gene duplication

Noda‐Garcia, Lianet; Barona‐Gómez, Francisco

doi:10.4161/mge.26439

Cited by 14 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The TrpF-1 sub-clade (red branch, Figure 2) represents the corynebacterial TrpF xenologues present in the Gammaproteobacteria . Thus, and as introduced above, TrpF-1 co-occurs with a sub-functionalized PriA, subHisA, which has lost its PRA isomerase function [14,15].…”

Section: Resultsmentioning

confidence: 99%

“…coli mutants lacking the trpF (strain FBGW f ) or hisA (strain HfrG6) genes. In addition, when possible, some of them were purified to homogeneity and characterized, as previously described [10,14,15]. Moreover, conversion of PRA by the TrpF-2 homologue from S. globisporus (PRaP_Sglo) was investigated.…”

Section: Resultsmentioning

confidence: 99%

“…The changes include different positions of residues away from the catalytic framework, with the most pronounced rearrangements and various degrees of order seen in the L5 loop. Interestingly, although loops 1 and 6 have been shown to adopt different conformations in PriA_Mtub, defining the apo and halo states [15,16], the PriA and PriB structures from Streptomyces species do not show these movements. So we focused on the several interactions that contribute to conformation and position of the L5 loop in PriB proteins, as further described below, with an emphasis on the contacts related to ProFAR and PRA substrates.…”

Section: Resultsmentioning

confidence: 99%

“…( C ) PriA from M. tuberculosis (PriA_Mtub) with L5 loop assuming a twisted knot-like conformation upon binding of PRFAR. All the known active site residues [15] are shown in both complexes.…”

Section: Figurementioning

confidence: 99%

“…PriA’s structure and function relationship has been also thoroughly investigated [8–11], and possible connections with other His and Trp enzymes have been proposed [12]. Moreover, given its physiologically relevant dual-substrate specificity, PriA has been adopted as a model system to study the evolution of the ( βα ) 8 -fold [12,13], and previously, to investigate genetic models driving enzyme evolution [3,14,15].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Co-occurrence of analogous enzymes determines evolution of a novel (βα)8-isomerase sub-family after non-conserved mutations in flexible loop

Verduzco-Castro

Michalska

Endres

et al. 2016

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

We investigate the evolution of co-occurring analogous enzymes involved in L-tryptophan and L-histidine biosynthesis in Actinobacteria Phylogenetic analysis of trpF homologues, a missing gene in certain clades of this lineage whose absence is complemented by a dual-substrate HisA homologue, termed PriA, found that they fall into three categories: (i) trpF-1, an L-tryptophan biosynthetic gene horizontally acquired by certain Corynebacterium species; (ii) trpF-2, a paralogue known to be involved in synthesizing a pyrrolopyrrole moiety and (iii) trpF-3, a variable non-conserved orthologue of trpF-1 We previously investigated the effect of trpF-1 upon the evolution of PriA substrate specificity, but nothing is known about the relationship between trpF-3 and priA After in vitro steady-state enzyme kinetics we found that trpF-3 encodes a phosphoribosyl anthranilate isomerase. However, mutation of this gene in Streptomyces sviceus did not lead to auxothrophy, as expected from the biosynthetic role of trpF-1 Biochemical characterization of a dozen co-occurring TrpF-2 or TrpF-3, with PriA homologues, explained the prototrophic phenotype, and unveiled an enzyme activity trade-off between TrpF and PriA. X-ray structural analysis suggests that the function of these PriA homologues is mediated by non-conserved mutations in the flexible L5 loop, which may be responsible for different substrate affinities. Thus, the PriA homologues that co-occur with TrpF-3 represent a novel enzyme family, termed PriB, which evolved in response to PRA isomerase activity. The characterization of co-occurring enzymes provides insights into the influence of functional redundancy on the evolution of enzyme function, which could be useful for enzyme functional annotation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Co-occurrence of analogous enzymes determines evolution of a novel (βα)8-isomerase sub-family after non-conserved mutations in flexible loop

Verduzco-Castro

Michalska

Endres

et al. 2016

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

show abstract

The Complexity of Genetic Redundancy

Krakauer

2014

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Genetic redundancy is often associated with the duplication of an open reading frame within a genome or a multiplicity of regulatory elements sharing a target. Genetic redundancy is inferred when the modification or deletion of a portion of functional genetic material results in minimal changes to a trait or organismal phenotype – robustness – and when this genetic information is surplus to a reference, non‐robust, genome. Robustness has been attributed to buffering mechanisms promoted by duplicates and to compensatory pathways that can be independent of duplication. Most redundant duplicates are rapidly lost from genomes by mutation and drift. The preservation of redundancy requires some form of epistasis or pleiotropy, typically evolving through subfunctionalization of gene products. The term redundancy is too coarse to capture the full range of phenomena that it is used to describe and new concepts are required for dealing with multi‐locus and context‐dependent robustness. Key Concepts: Redundancy arises through mechanisms that compensate for the loss of functional genetic information. Redundancy can be achieved through a duplication of a structural or regulatory gene. Redundancy arises neutrally through partial or whole‐genome duplication and can persist without selection for short periods of time. The long‐term preservation of redundancy requires specific genetic mechanisms, epistastis or pleiotropy, and on‐going selection pressures. Redundancy is most common in species found in small populations with large genomes for whom neutral processes, dominated by drift, play a significant role. Genetic or structural similarity among perturbed (knockout or knockdown) duplicates, to imply functional interchangeability, is empirically the strongest predictor of genetic redundancy. Alternative, functionally equivalent pathways, that do not share genetic duplicates, can provide mechanisms of redundancy. Redundancy is context‐dependent and often involves numerous factors to include epigenetic modification, environmental compensation, not just genetic loci. Recent studies showing a very high incidence of loss‐function variants in human genomes provide strong support for the prevalence of mechanisms of redundancy. New concepts are required to capture the robustness of genomes that go beyond mechanisms of redundancy. These new concepts will need to deal effectively with the contribution of numerous loci and factors – collective robustness.

show abstract

Dynamics and constraints of enzyme evolution

Kaltenbach

Tokuriki

2014

J Exp Zool Pt B

View full text Add to dashboard Cite

The wealth of distinct enzymatic functions found in nature is impressive and the on-going evolutionary divergence of enzymatic functions continues to generate new and efficient catalysts, which can be seen through the recent emergence of enzymes able to degrade xenobiotics. However, recreating such processes in the laboratory has been met with only moderate success. What are the factors that lead to suboptimal research outputs? In this review, we discuss constraints on enzyme evolution, which can restrict evolutionary trajectories and lead to evolutionary dead-ends. We highlight recent studies that have used experimental evolution to mimic different aspects of enzymatic adaptation under simple, controlled settings to shed light on evolutionary dynamics and constraints. A better understanding of these constraints will lead to the development of more efficient strategies for directed evolution and enzyme engineering.

show abstract

Enzyme evolution beyond gene duplication

Cited by 14 publications

References 24 publications

Co-occurrence of analogous enzymes determines evolution of a novel (βα)8-isomerase sub-family after non-conserved mutations in flexible loop

Co-occurrence of analogous enzymes determines evolution of a novel (βα)8-isomerase sub-family after non-conserved mutations in flexible loop

The Complexity of Genetic Redundancy

Dynamics and constraints of enzyme evolution

Contact Info

Product

Resources

About