Special Issue "Evolution and Structure of Proteins and Proteomes"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Population and Evolutionary Genetics and Genomics".

Deadline for manuscript submissions: closed (31 May 2018)

Special Issue Editors

Guest Editor
Dr. David Liberles

Department of Biology, Temple University, Philadelphia, PA, USA
Website | E-Mail
Interests: comparative genomics; protein evolution; computational evolutionary systems biology; gene duplication
Guest Editor
Dr. Ashley Teufel

Department of Integrative Biology, University of Austin Texas, Austin, TX, USA
Website | E-Mail
Interests: protein evolution; gene duplication; computational biology; virology

Special Issue Information

Dear Colleagues, 

The evolution of proteins and proteomes is governed by a wealth of interacting processes, spanning from the population level to the atomic level. When a mutation appears in a protein coding sequence, its ultimate fate in a population depends, in part, on its effects on functional sites, folding and stability, and expression. Even subtle modifications to any of these components can have downstream effects on systems-level processes that influence individual fitness. Although these molecular processes occur within an individual, their evolutionary consequences are determined by the population into which they are cast. In this Special Issue, we encourage the contribution of review articles and original research papers that examine the evolution and structure of proteins and proteomes through a merger of biophysics, systems biology, evolutionary, and population genetic frameworks.

Dr. David Liberles
Dr. Ashley Teufel
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • protein
  • proteome
  • evolution
  • molecular function
  • biophysical models
  • evolutionary systems biology
  • biological networks

Published Papers (6 papers)

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Research

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Open AccessArticle Selection for Protein Stability Enriches for Epistatic Interactions
Received: 4 June 2018 / Revised: 30 July 2018 / Accepted: 14 August 2018 / Published: 21 August 2018
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Abstract
A now classical argument for the marginal thermodynamic stability of proteins explains the distribution of observed protein stabilities as a consequence of an entropic pull in protein sequence space. In particular, most sequences that are sufficiently stable to fold will have stabilities near
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A now classical argument for the marginal thermodynamic stability of proteins explains the distribution of observed protein stabilities as a consequence of an entropic pull in protein sequence space. In particular, most sequences that are sufficiently stable to fold will have stabilities near the folding threshold. Here, we extend this argument to consider its predictions for epistatic interactions for the effects of mutations on the free energy of folding. Although there is abundant evidence to indicate that the effects of mutations on the free energy of folding are nearly additive and conserved over evolutionary time, we show that these observations are compatible with the hypothesis that a non-additive contribution to the folding free energy is essential for observed proteins to maintain their native structure. In particular, through both simulations and analytical results, we show that even very small departures from additivity are sufficient to drive this effect. Full article
(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes)
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Open AccessArticle Structural and Evolutionary Insights within the Polysaccharide Deacetylase Gene Family of Bacillus anthracis and Bacillus cereus
Received: 31 May 2018 / Revised: 24 July 2018 / Accepted: 25 July 2018 / Published: 31 July 2018
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Abstract
Functional and folding constraints impose interdependence between interacting sites along the protein chain that are envisaged through protein sequence evolution. Studying the influence of structure in phylogenetic models requires detailed and reliable structural models. Polysaccharide deacetylases (PDAs), members of the carbohydrate esterase family
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Functional and folding constraints impose interdependence between interacting sites along the protein chain that are envisaged through protein sequence evolution. Studying the influence of structure in phylogenetic models requires detailed and reliable structural models. Polysaccharide deacetylases (PDAs), members of the carbohydrate esterase family 4, perform mainly metal-dependent deacetylation of O- or N-acetylated polysaccharides such as peptidoglycan, chitin and acetylxylan through a conserved catalytic core termed the NodB homology domain. Genomes of Bacillus anthracis and its relative Bacillus cereus contain multiple genes of putative or known PDAs. A comparison of the functional domains of the recently determined PDAs from B. anthracis and B. cereus and multiple amino acid and nucleotide sequence alignments and phylogenetic analysis performed on these closely related species showed that there were distinct differences in binding site formation, despite the high conservation on the protein sequence, the folding level and the active site assembly. This may indicate that, subject to biochemical verification, the binding site-forming sequence fragments are under functionally driven evolutionary pressure to accommodate and recognize distinct polysaccharide residues according to cell location, use, or environment. Finally, we discuss the suggestion of the paralogous nature of at least two genes of B. anthracis, ba0330 and ba0331, via specific differences in gene sequence, protein structure, selection pressure and available localization patterns. This study may contribute to understanding the mechanisms under which sequences evolve in their structures and how evolutionary processes enable structural variations. Full article
(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes)
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Open AccessArticle Morphological Stasis and Proteome Innovation in Cephalochordates
Received: 24 May 2018 / Revised: 11 July 2018 / Accepted: 11 July 2018 / Published: 16 July 2018
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Abstract
Lancelets, extant representatives of basal chordates, are prototypic examples of evolutionary stasis; they preserved a morphology and body-plan most similar to the fossil chordates from the early Cambrian. Such a low level of morphological evolution is in harmony with a low rate of
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Lancelets, extant representatives of basal chordates, are prototypic examples of evolutionary stasis; they preserved a morphology and body-plan most similar to the fossil chordates from the early Cambrian. Such a low level of morphological evolution is in harmony with a low rate of amino acid substitution; cephalochordate proteins were shown to evolve slower than those of the slowest evolving vertebrate, the elephant shark. Surprisingly, a study comparing the predicted proteomes of Chinese amphioxus, Branchiostoma belcheri and the Florida amphioxus, Branchiostoma floridae has led to the conclusion that the rate of creation of novel domain combinations is orders of magnitude greater in lancelets than in any other Metazoa, a finding that contradicts the notion that high rates of protein innovation are usually associated with major evolutionary innovations. Our earlier studies on a representative sample of proteins have provided evidence suggesting that the differences in the domain architectures of predicted proteins of these two lancelet species reflect annotation errors, rather than true innovations. In the present work, we have extended these studies to include a larger sample of genes and two additional lancelet species, Asymmetron lucayanum and Branchiostoma lanceolatum. These analyses have confirmed that the domain architecture differences of orthologous proteins of the four lancelet species are because of errors of gene prediction, the error rate in the given species being inversely related to the quality of the transcriptome dataset that was used to aid gene prediction. Full article
(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes)
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Open AccessArticle Epistatic Interactions in NS5A of Hepatitis C Virus Suggest Drug Resistance Mechanisms
Received: 27 March 2018 / Accepted: 29 June 2018 / Published: 6 July 2018
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Abstract
Hepatitis C virus (HCV) causes a major health burden and can be effectively treated by direct-acting antivirals (DAAs). The non-structural protein 5A (NS5A), which plays a role in the viral genome replication, is one of the DAAs’ targets. Resistance-associated viruses (RAVs) harbouring NS5A
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Hepatitis C virus (HCV) causes a major health burden and can be effectively treated by direct-acting antivirals (DAAs). The non-structural protein 5A (NS5A), which plays a role in the viral genome replication, is one of the DAAs’ targets. Resistance-associated viruses (RAVs) harbouring NS5A resistance-associated mutations (RAMs) have been described at baseline and after therapy failure. A mutation from glutamine to arginine at position 30 (Q30R) is a characteristic RAM for the HCV sub/genotype (GT) 1a, but arginine corresponds to the wild type in the GT-1b; still, GT-1b strains are susceptible to NS5A-inhibitors. In this study, we show that GT-1b strains with R30Q often display other specific NS5A substitutions, particularly in positions 24 and 34. We demonstrate that in GT-1b secondary substitutions usually happen after initial R30Q development in the phylogeny, and that the chemical properties of the corresponding amino acids serve to restore the positive charge in this region, acting as compensatory mutations. These findings may have implications for RAVs treatment. Full article
(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes)
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Review

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Open AccessReview Using the Mutation-Selection Framework to Characterize Selection on Protein Sequences
Received: 19 June 2018 / Revised: 2 August 2018 / Accepted: 9 August 2018 / Published: 13 August 2018
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Abstract
When mutational pressure is weak, the generative process of protein evolution involves explicit probabilities of mutations of different types coupled to their conditional probabilities of fixation dependent on selection. Establishing this mechanistic modeling framework for the detection of selection has been a goal
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When mutational pressure is weak, the generative process of protein evolution involves explicit probabilities of mutations of different types coupled to their conditional probabilities of fixation dependent on selection. Establishing this mechanistic modeling framework for the detection of selection has been a goal in the field of molecular evolution. Building on a mathematical framework proposed more than a decade ago, numerous methods have been introduced in an attempt to detect and measure selection on protein sequences. In this review, we discuss the structure of the original model, subsequent advances, and the series of assumptions that these models operate under. Full article
(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes)
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Open AccessFeature PaperReview Evolutionary Divergent Suppressor Mutations in Conformational Diseases
Received: 12 June 2018 / Revised: 9 July 2018 / Accepted: 11 July 2018 / Published: 13 July 2018
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Abstract
Neutral and adaptive mutations are key players in the evolutionary dynamics of proteins at molecular, cellular and organismal levels. Conversely, largely destabilizing mutations are rarely tolerated by evolution, although their occurrence in diverse human populations has important roles in the pathogenesis of conformational
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Neutral and adaptive mutations are key players in the evolutionary dynamics of proteins at molecular, cellular and organismal levels. Conversely, largely destabilizing mutations are rarely tolerated by evolution, although their occurrence in diverse human populations has important roles in the pathogenesis of conformational diseases. We have recently proposed that divergence at certain sites from the consensus (amino acid) state during mammalian evolution may have rendered some human proteins more vulnerable towards disease-associated mutations, primarily by decreasing their conformational stability. We herein extend and refine this hypothesis discussing results from phylogenetic and structural analyses, structure-based energy calculations and structure-function studies at molecular and cellular levels. As proof-of-principle, we focus on different mammalian orthologues of the NQO1 (NAD(P)H:quinone oxidoreductase 1) and AGT (alanine:glyoxylate aminotransferase) proteins. We discuss the different loss-of-function pathogenic mechanisms associated with diseases involving the two enzymes, including enzyme inactivation, accelerated degradation, intracellular mistargeting, and aggregation. Last, we take into account the potentially higher robustness of mammalian orthologues containing certain consensus amino acids as suppressors of human disease, and their relation with different intracellular post-translational modifications and protein quality control capacities, to be discussed as sources of phenotypic variability between human and mammalian models of disease and as tools for improving current therapeutic approaches. Full article
(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes)
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