scholarly journals Mistranslation can promote the exploration of alternative evolutionary trajectories in enzyme evolution

2021 ◽  
Author(s):  
Jia Zheng ◽  
Sinisa Bratulic ◽  
Heidi E. L. Lischer ◽  
Andreas Wagner
Keyword(s):  
Enzyme Evolution ◽  
Evolutionary Trajectories

Multidimensional epistasis and fitness landscapes in enzyme evolution

2012 ◽  
Vol 445 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Wei Zhang ◽  
Daniel F. A. R. Dourado ◽  
Pedro Alexandrino Fernandes ◽  
Maria João Ramos ◽  
Bengt Mannervik
Keyword(s):  
Glutathione Transferase ◽  
Fitness Landscape ◽  
Evolutionary Process ◽  
Salient Feature ◽  
Selective Advantage ◽  
Enzyme Evolution ◽  
Conventional Analysis ◽  
Evolutionary Response ◽  
Single Protein ◽  
Evolutionary Trajectories

The conventional analysis of enzyme evolution is to regard one single salient feature as a measure of fitness, expressed in a milieu exposing the possible selective advantage at a given time and location. Given that a single protein may serve more than one function, fitness should be assessed in several dimensions. In the present study we have explored individual mutational steps leading to a triple-point-mutated human GST (glutathione transferase) A2-2 displaying enhanced activity with azathioprine. A total of eight alternative substrates were used to monitor the diverse evolutionary trajectories. The epistatic effects of the mutations on catalytic activity were variable in sign and magnitude and depended on the substrate used, showing that epistasis is a multidimensional quality. Evidently, the multidimensional fitness landscape can lead to alternative trajectories resulting in enzymes optimized for features other than the selectable markers relevant at the origin of the evolutionary process. In this manner the evolutionary response is robust and can adapt to changing environmental conditions.

Multi-substrate–activity space and quasi-species in enzyme evolution: Ohno's dilemma, promiscuity and functional orthogonality

2009 ◽  
Vol 37 (4) ◽  
pp. 740-744 ◽  
Author(s):  
Bengt Mannervik ◽  
Arna Runarsdottir ◽  
Sanela Kurtovic
Keyword(s):  
Multivariate Analysis ◽  
Directed Evolution ◽  
Enzyme Evolution ◽  
Activity Space ◽  
Glutathione Transferases ◽  
Multidimensional Space ◽  
Alternative Substrates ◽  
Catalytic Activities ◽  
Evolutionary Trajectories

A functional enzyme displays activity with at least one substrate and can be represented by a vector in substrate–activity space. Many enzymes, including GSTs (glutathione transferases), are promiscuous in the sense that they act on alternative substrates, and the corresponding vectors operate in multidimensional space. The direction of the vector is governed by the relative activities of the diverse substrates. Stochastic mutations of already existing enzymes generate populations of variants, and clusters of functionally similar mutants can serve as parents for subsequent generations of enzymes. The proper evolving unit is a functional quasi-species, which may not be identical with the ‘best’ variant in its generation. The manifestation of the quasi-species is dependent on the substrate matrix used to explore catalytic activities. Multivariate analysis is an approach to identifying quasi-species and to investigate evolutionary trajectories in the directed evolution of enzymes for novel functions.

scholarly journals Conformational dynamics and enzyme evolution

2018 ◽  
Vol 15 (144) ◽  
pp. 20180330 ◽  
Author(s):  
Dušan Petrović ◽  
Valeria A. Risso ◽  
Shina Caroline Lynn Kamerlin ◽  
Jose M. Sanchez-Ruiz
Keyword(s):  
Biological Function ◽  
Dynamic Properties ◽  
Conformational Dynamics ◽  
Enzyme Evolution ◽  
Single Mutation ◽  
Evolutionary Changes ◽  
Conformational Diversity ◽  
Evolutionary Trajectories ◽  
Experimental Approaches ◽  
Environmental Temperatures

Enzymes are dynamic entities, and their dynamic properties are clearly linked to their biological function. It follows that dynamics ought to play an essential role in enzyme evolution. Indeed, a link between conformational diversity and the emergence of new enzyme functionalities has been recognized for many years. However, it is only recently that state-of-the-art computational and experimental approaches are revealing the crucial molecular details of this link. Specifically, evolutionary trajectories leading to functional optimization for a given host environment or to the emergence of a new function typically involve enriching catalytically competent conformations and/or the freezing out of non-competent conformations of an enzyme. In some cases, these evolutionary changes are achieved through distant mutations that shift the protein ensemble towards productive conformations. Multifunctional intermediates in evolutionary trajectories are probably multi-conformational, i.e. able to switch between different overall conformations, each competent for a given function. Conformational diversity can assist the emergence of a completely new active site through a single mutation by facilitating transition-state binding. We propose that this mechanism may have played a role in the emergence of enzymes at the primordial, progenote stage, where it was plausibly promoted by high environmental temperatures and the possibility of additional phenotypic mutations.

scholarly journals Skull shape differentiation of black and white olms (Proteus anguinus anguinus and Proteus a. parkelj): an exploratory analysis with micro-CT scanning

2013 ◽  
Vol 82 (2) ◽  
pp. 107-114 ◽  
Author(s):  
Ana Ivanović ◽  
Gregor Aljančič ◽  
Jan W. Arntzen
Keyword(s):  
Morphological Differentiation ◽  
Ct Scanning ◽  
Exploratory Analysis ◽  
Micro Ct ◽  
Black And White ◽  
Necturus Maculosus ◽  
Proteus Anguinus ◽  
Evolutionary Trajectories ◽  
Morphological Detail ◽  
Shape Changes

We performed an exploratory analysis of the morphology of the cranium in the white olm (Proteus anguinus anguinus) and the black olm (P. a. parkelj) with micro-CT scanning and geometric morphometrics. The mudpuppy (Necturus maculosus) was used as an outgroup. The black olm falls outside the white olm morphospace by a markedly wider skull, shorter vomers which are positioned further apart and by laterally positioned squamosals and quadrates relative to the palate (the shape of the buccal cavity). On account of its robust skull with more developed premaxillae a shorter otico-occipital region, the black olm is positioned closer to Necturus than are the studied specimens of the white olm. The elongated skull of the white olm, with an anteriorly positioned jaw articulation point, could be regarded as an adaptation for improved feeding success, possibly compensating for lack of vision. As yet, the alternative explanations on the evolution of troglomorphism in Proteus are an extensive convergence in white olms versus the reverse evolution towards less troglomorphic character states in the black olm. To further understand the evolutionary trajectories within Proteus we highlight the following hypotheses for future testing: i) morphological differentiation is smaller within than between genetically differentiated white olm lineages, and ii) ontogenetic shape changes are congruent with the shape changes between lineages. We anticipate that the morphological detail and analytical power that come with the techniques we here employed will assist us in this task.

scholarly journals Impacts of yeast metabolic network structure on enzyme evolution

2007 ◽  
Vol 8 (8) ◽  
pp. 407 ◽  
Author(s):  
Chenqi Lu ◽  
Ze Zhang ◽  
Lindsey Leach ◽  
MJ Kearsey ◽  
ZW Luo
Keyword(s):  
Metabolic Network ◽  
Network Structure ◽  
Enzyme Evolution

scholarly journals Mutational patterns and clonal evolution from diagnosis to relapse in pediatric acute lymphoblastic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shumaila Sayyab ◽  
Anders Lundmark ◽  
Malin Larsson ◽  
Markus Ringnér ◽  
Sara Nystedt ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Large Scale ◽  
Somatic Mutations ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Point Mutations ◽  
Driver Genes ◽  
Protein Coding ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Evolutionary Trajectories

AbstractThe mechanisms driving clonal heterogeneity and evolution in relapsed pediatric acute lymphoblastic leukemia (ALL) are not fully understood. We performed whole genome sequencing of samples collected at diagnosis, relapse(s) and remission from 29 Nordic patients. Somatic point mutations and large-scale structural variants were called using individually matched remission samples as controls, and allelic expression of the mutations was assessed in ALL cells using RNA-sequencing. We observed an increased burden of somatic mutations at relapse, compared to diagnosis, and at second relapse compared to first relapse. In addition to 29 known ALL driver genes, of which nine genes carried recurrent protein-coding mutations in our sample set, we identified putative non-protein coding mutations in regulatory regions of seven additional genes that have not previously been described in ALL. Cluster analysis of hundreds of somatic mutations per sample revealed three distinct evolutionary trajectories during ALL progression from diagnosis to relapse. The evolutionary trajectories provide insight into the mutational mechanisms leading relapse in ALL and could offer biomarkers for improved risk prediction in individual patients.

scholarly journals The Diversity and Evolution of Sex Chromosomes in Frogs

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 483
Author(s):  
Wen-Juan Ma ◽  
Paris Veltsos
Keyword(s):  
Sex Determination ◽  
Sex Chromosomes ◽  
Chromosome Evolution ◽  
Sex Chromosome ◽  
Comparative Genomic ◽  
Ancestral State ◽  
Heteromorphic Sex Chromosomes ◽  
Genomic Studies ◽  
Evolutionary Trajectories ◽  
Heterogametic Sex

Frogs are ideal organisms for studying sex chromosome evolution because of their diversity in sex chromosome differentiation and sex-determination systems. We review 222 anuran frogs, spanning ~220 Myr of divergence, with characterized sex chromosomes, and discuss their evolution, phylogenetic distribution and transitions between homomorphic and heteromorphic states, as well as between sex-determination systems. Most (~75%) anurans have homomorphic sex chromosomes, with XY systems being three times more common than ZW systems. Most remaining anurans (~25%) have heteromorphic sex chromosomes, with XY and ZW systems almost equally represented. There are Y-autosome fusions in 11 species, and no W-/Z-/X-autosome fusions are known. The phylogeny represents at least 19 transitions between sex-determination systems and at least 16 cases of independent evolution of heteromorphic sex chromosomes from homomorphy, the likely ancestral state. Five lineages mostly have heteromorphic sex chromosomes, which might have evolved due to demographic and sexual selection attributes of those lineages. Males do not recombine over most of their genome, regardless of which is the heterogametic sex. Nevertheless, telomere-restricted recombination between ZW chromosomes has evolved at least once. More comparative genomic studies are needed to understand the evolutionary trajectories of sex chromosomes among frog lineages, especially in the ZW systems.

scholarly journals CRISPR-Cas System: The Powerful Modulator of Accessory Genomes in Prokaryotes

2021 ◽  
pp. 1-16
Author(s):  
Anca Butiuc-Keul ◽  
Anca Farkas ◽  
Rahela Carpa ◽  
Dumitrana Iordache
Keyword(s):  
Nucleic Acids ◽  
Pathogenic Bacteria ◽  
The Novel ◽  
Defense System ◽  
Guide Rnas ◽  
Crispr Array ◽  
Different Types ◽  
Evolutionary Trajectories ◽  
Novel Coronavirus ◽  
Cas Proteins

Being frequently exposed to foreign nucleic acids, bacteria and archaea have developed an ingenious adaptive defense system, called CRISPR-Cas. The system is composed of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) array, together with CRISPR (<i>cas</i>)-associated genes. This system consists of a complex machinery that integrates fragments of foreign nucleic acids from viruses and mobile genetic elements (MGEs), into CRISPR arrays. The inserted segments (spacers) are transcribed and then used by cas proteins as guide RNAs for recognition and inactivation of the targets. Different types and families of CRISPR-Cas systems consist of distinct adaptation and effector modules with evolutionary trajectories, partially independent. The origin of the effector modules and the mechanism of spacer integration/deletion is far less clear. A review of the most recent data regarding the structure, ecology, and evolution of CRISPR-Cas systems and their role in the modulation of accessory genomes in prokaryotes is proposed in this article. The CRISPR-Cas system&apos;s impact on the physiology and ecology of prokaryotes, modulation of horizontal gene transfer events, is also discussed here. This system gained popularity after it was proposed as a tool for plant and animal embryo editing, in cancer therapy, as antimicrobial against pathogenic bacteria, and even for combating the novel coronavirus – SARS-CoV-2; thus, the newest and promising applications are reviewed as well.

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