Editorial

2 pages, 173 KiB

Open AccessEditorial

Evolution and Structure of Proteins and Proteomes

by David A. Liberles and Ashley I. Teufel

Genes 2018, 9(12), 583; https://doi.org/10.3390/genes9120583 - 28 Nov 2018

Cited by 2 | Viewed by 2198

This themed issue centered on the evolution and structure of proteins and proteomes is comprised of seven published manuscripts. [...] Full article

(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes)

Research

Jump to: Editorial, Review

15 pages, 3876 KiB

Open AccessArticle

Large-Scale Analyses of Site-Specific Evolutionary Rates across Eukaryote Proteomes Reveal Confounding Interactions between Intrinsic Disorder, Secondary Structure, and Functional Domains

by Joseph B. Ahrens, Jordon Rahaman and Jessica Siltberg-Liberles

Genes 2018, 9(11), 553; https://doi.org/10.3390/genes9110553 - 14 Nov 2018

Cited by 10 | Viewed by 3798

Abstract

Various structural and functional constraints govern the evolution of protein sequences. As a result, the relative rates of amino acid replacement among sites within a protein can vary significantly. Previous large-scale work on Metazoan (Animal) protein sequence alignments indicated that amino acid replacement [...] Read more.

Various structural and functional constraints govern the evolution of protein sequences. As a result, the relative rates of amino acid replacement among sites within a protein can vary significantly. Previous large-scale work on Metazoan (Animal) protein sequence alignments indicated that amino acid replacement rates are partially driven by a complex interaction among three factors: intrinsic disorder propensity; secondary structure; and functional domain involvement. Here, we use sequence-based predictors to evaluate the effects of these factors on site-specific sequence evolutionary rates within four eukaryotic lineages: Metazoans; Plants; Saccharomycete Fungi; and Alveolate Protists. Our results show broad, consistent trends across all four Eukaryote groups. In all four lineages, there is a significant increase in amino acid replacement rates when comparing: (i) disordered vs. ordered sites; (ii) random coil sites vs. sites in secondary structures; and (iii) inter-domain linker sites vs. sites in functional domains. Additionally, within Metazoans, Plants, and Saccharomycetes, there is a strong confounding interaction between intrinsic disorder and secondary structure—alignment sites exhibiting both high disorder propensity and involvement in secondary structures have very low average rates of sequence evolution. Analysis of gene ontology (GO) terms revealed that in all four lineages, a high fraction of sequences containing these conserved, disordered-structured sites are involved in nucleic acid binding. We also observe notable differences in the statistical trends of Alveolates, where intrinsically disordered sites are more variable than in other Eukaryotes and the statistical interactions between disorder and other factors are less pronounced. Full article

(This article belongs to the Special Issue Evolution and Structure of Proteins and Proteomes)

► Show Figures

Figure 1

19 pages, 976 KiB

Open AccessArticle

Selection for Protein Stability Enriches for Epistatic Interactions

by Anna Posfai, Juannan Zhou, Joshua B. Plotkin, Justin B. Kinney and David M. McCandlish

Genes 2018, 9(9), 423; https://doi.org/10.3390/genes9090423 - 21 Aug 2018

Cited by 5 | Viewed by 4429

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 [...] Read more.

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)

► Show Figures

Figure 1

23 pages, 9807 KiB

Open AccessArticle

Structural and Evolutionary Insights within the Polysaccharide Deacetylase Gene Family of Bacillus anthracis and Bacillus cereus

by Athena Andreou, Petros Giastas, Elias Christoforides and Elias E. Eliopoulos

Genes 2018, 9(8), 386; https://doi.org/10.3390/genes9080386 - 31 Jul 2018

Cited by 14 | Viewed by 6634

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 [...] Read more.

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)

► Show Figures

Graphical abstract

13 pages, 1321 KiB

Open AccessArticle

Morphological Stasis and Proteome Innovation in Cephalochordates

by László Bányai, Krisztina Kerekes, Mária Trexler and László Patthy

Genes 2018, 9(7), 353; https://doi.org/10.3390/genes9070353 - 16 Jul 2018

Cited by 2 | Viewed by 3203

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 [...] Read more.

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)

► Show Figures

Figure 1

16 pages, 1235 KiB

Open AccessArticle

Epistatic Interactions in NS5A of Hepatitis C Virus Suggest Drug Resistance Mechanisms

by Elena Knops, Saleta Sierra, Prabhav Kalaghatgi, Eva Heger, Rolf Kaiser and Olga V. Kalinina

Genes 2018, 9(7), 343; https://doi.org/10.3390/genes9070343 - 06 Jul 2018

Cited by 12 | Viewed by 5056

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 [...] Read more.

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)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

12 pages, 2028 KiB

Open AccessReview

Using the Mutation-Selection Framework to Characterize Selection on Protein Sequences

by Ashley I. Teufel, Andrew M. Ritchie, Claus O. Wilke and David A. Liberles

Genes 2018, 9(8), 409; https://doi.org/10.3390/genes9080409 - 13 Aug 2018

Cited by 9 | Viewed by 3716

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 [...] Read more.

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)

► Show Figures

Figure 1

21 pages, 7001 KiB

Open AccessFeature PaperReview

Evolutionary Divergent Suppressor Mutations in Conformational Diseases

by Noel Mesa-Torres, Isabel Betancor-Fernández, Elisa Oppici, Barbara Cellini, Eduardo Salido and Angel L. Pey

Genes 2018, 9(7), 352; https://doi.org/10.3390/genes9070352 - 13 Jul 2018

Cited by 13 | Viewed by 3420

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 [...] Read more.

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)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Evolution and Structure of Proteins and Proteomes

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (8 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI