scholarly journals The missing expression level-evolutionary rate anticorrelation in viruses does not support protein function as a main constraint on sequence evolution

2021 ◽  
Author(s):  
Changshuo Wei ◽  
Yan-Ming Chen ◽  
Ying Chen ◽  
Wenfeng Qian
Keyword(s):  
Protein Function ◽  
Viral Protein ◽  
Evolutionary Biology ◽  
Evolutionary Rate ◽  
Purifying Selection ◽  
Endogenous Retroviruses ◽  
Expression Level ◽  
Sequence Evolution ◽  
Virus Species ◽  
Selective Constraints

Abstract One of the central goals in molecular evolutionary biology is to determine the sources of variation in the rate of sequence evolution among proteins. Gene expression level is widely accepted as the primary determinant of protein evolutionary rate, because it scales with the extent of selective constraints imposed on a protein, leading to the well-known negative correlation between expression level and protein evolutionary rate (the E-R anticorrelation). Selective constraints have been hypothesized to entail the maintenance of protein function, the avoidance of cytotoxicity caused by protein misfolding or nonspecific protein-protein interactions, or both. However, empirical tests evaluating the relative importance of these hypotheses remain scarce, likely due to the non-trivial difficulties in distinguishing the effect of a deleterious mutation on a protein’s function vs. its cytotoxicity. We realized that examining the sequence evolution of viral proteins could overcome this hurdle. It is because purifying selection against mutations in a viral protein that result in cytotoxicity per se is likely relaxed, while purifying selection against mutations that impair viral protein function persists. Multiple analyses of SARS-CoV-2 and nine other virus species revealed a complete absence of any E-R anticorrelation. As a control, the E-R anticorrelation does exist in human endogenous retroviruses where purifying selection against cytotoxicity is present. Taken together, these observations do not support the maintenance of protein function as the main constraint on protein sequence evolution in cellular organisms.

scholarly journals Evolutionary rate coevolution between mitochondria and mitochondria-associated nuclear-encoded proteins in insects

2018 ◽  
Author(s):  
Zhichao Yan ◽  
Gongyin Ye ◽  
John H. Werren
Keyword(s):  
Mitochondrial Function ◽  
Evolutionary Biology ◽  
Evolutionary Rate ◽  
Strong Predictor ◽  
Nuclear Proteins ◽  
Sequence Evolution ◽  
Minichromosome Maintenance ◽  
Encoded Proteins ◽  
Associated Proteins ◽  
Protein Conservation

AbstractThe mitochondrion is a pivotal organelle for energy production, and includes components encoded by both the mitochondrial and nuclear genomes. How these two genomes coevolve is a long-standing question in evolutionary biology. Here we initially investigate the evolutionary rates of mitochondrial components (oxidative phosphorylation (OXPHOS) proteins and ribosomal RNAs) and nuclear-encoded proteins associated with mitochondria, across the major orders of holometabolous insects. There are significant evolutionary rate correlations (ERCs) between mitochondria and mitochondria-associated nuclear-encoded proteins, which is likely driven by different rates of mitochondrial sequence evolution and compensatory changes in the interacting nuclear-encoded proteins. The pattern holds after correction for phylogenetic relationships and considering protein conservation levels. Correlations are stronger for nuclear-encoded OXPHOS proteins in contact with mitochondrial-encoded OXPHOS proteins and nuclear-encoded mitochondrial ribosomal amino acids directly contacting the mitochondrial rRNA. Mitochondrial-associated proteins show apparent rate acceleration over evolutionary time, but we suspect this pattern to be due to artifacts (e.g. rate estimation or calibration bias). We find that ERC between mitochondrial and nuclear proteins is a strong predictor of nuclear proteins known to interact with mitochondria, and therefore ERCs can be used to predict new candidate nuclear proteins with mitochondrial function. Using this approach, we detect proteins with high ERCs but not with known mitochondrial function based on gene ontology (GO). Manual screening of the literature revealed potential mitochondrial function for some of these proteins in humans or yeast. Their holometabolous ERCs therefore indicate these proteins may have phylogenetically conserved mitochondrial function. Twenty three additional candidates warrant further study for mitochondrial function based on this approach, including ERC evidence that proteins in the minichromosome maintenance helicase (MCM) complex interact with mitochondria. We conclude that the ERC method shows promise for identifying new candidate proteins with mitochondrial function.

scholarly journals Tissue-specific evolution of protein coding genes in human and mouse

2014 ◽  
Author(s):  
Nadezda Kryuchkova-Mostacci ◽  
Marc Robinson-Rechavi
Keyword(s):  
Gene Expression ◽  
Positive Selection ◽  
Evolutionary Rate ◽  
Purifying Selection ◽  
Expression Level ◽  
Neutral Evolution ◽  
Protein Coding ◽  
Tissue Specific ◽  
Protein Coding Genes ◽  
Mouse Tissues

Protein-coding genes evolve at different rates, and the influence of different parameters, from gene size to expression level, has been extensively studied. While in yeast gene expression level is the major causal factor of gene evolutionary rate, the situation is more complex in animals. Here we investigate these relations further, especially taking in account gene expression in different organs as well as indirect correlations between parameters. We used RNA-seq data from two large datasets, covering 22 mouse tissues and 27 human tissues. Over all tissues, evolutionary rate only correlates weakly with levels and breadth of expression. The strongest explanatory factors of strong purifying selection are GC content, expression in many developmental stages, and expression in brain tissues. While the main component of evolutionary rate is purifying selection, we also find tissue-specific patterns for sites under neutral evolution and for positive selection. We observe fast evolution of genes expressed in testis, but also in other tissues, notably liver, which are explained by weak purifying selection rather than by positive selection.

scholarly journals Transcriptome Expression of Biomineralization Genes in Littoraria flava Gastropod in Brazilian Rocky Shore Reveals Evidence of Local Adaptation

2021 ◽  
Vol 13 (4) ◽  
Author(s):  
Camilla A Santos ◽  
Gabriel G Sonoda ◽  
Thainá Cortez ◽  
Luiz L Coutinho ◽  
Sónia C S Andrade
Keyword(s):  
Local Adaptation ◽  
Differentially Expressed Genes ◽  
Evolutionary Biology ◽  
Rocky Shore ◽  
Expression Patterns ◽  
Purifying Selection ◽  
Marine Species ◽  
Differentially Expressed ◽  
Planktonic Larva ◽  
Structure Changes

Abstract Understanding how selection shapes population differentiation and local adaptation in marine species remains one of the greatest challenges in the field of evolutionary biology. The selection of genes in response to environment-specific factors and microenvironmental variation often results in chaotic genetic patchiness, which is commonly observed in rocky shore organisms. To identify these genes, the expression profile of the marine gastropod Littoraria flava collected from four Southeast Brazilian locations in ten rocky shore sites was analyzed. In this first L. flava transcriptome, 250,641 unigenes were generated, and 24% returned hits after functional annotation. Independent paired comparisons between 1) transects, 2) sites within transects, and 3) sites from different transects were performed for differential expression, detecting 8,622 unique differentially expressed genes. Araçá (AR) and São João (SJ) transect comparisons showed the most divergent gene products. For local adaptation, fitness-related differentially expressed genes were chosen for selection tests. Nine and 24 genes under adaptative and purifying selection, respectively, were most related to biomineralization in AR and chaperones in SJ. The biomineralization-genes perlucin and gigasin-6 were positively selected exclusively in the site toward the open ocean in AR, with sequence variants leading to pronounced protein structure changes. Despite an intense gene flow among L. flava populations due to its planktonic larva, gene expression patterns within transects may be the result of selective pressures. Our findings represent the first step in understanding how microenvironmental genetic variation is maintained in rocky shore populations and the mechanisms underlying local adaptation in marine species.

Genomic Background Predicts the Fate of Duplicated Genes: Evidence From the Yeast Genome

Genetics ◽  
2004 ◽  
Vol 166 (4) ◽  
pp. 1995-1999 ◽  
Author(s):  
Ze Zhang ◽  
Hirohisa Kishino
Keyword(s):  
Recombination Rate ◽  
Evolutionary Rate ◽  
Average Rate ◽  
Classical Model ◽  
Purifying Selection ◽  
Genomic Region ◽  
Yeast Genome ◽  
Duplicated Genes ◽  
Potential Force ◽  
Accelerated Evolution

Abstract Gene duplication with subsequent divergence plays a central role in the acquisition of genes with novel function and complexity during the course of evolution. With reduced functional constraints or through positive selection, these duplicated genes may experience accelerated evolution. Under the model of subfunctionalization, loss of subfunctions leads to complementary acceleration at sites with two copies, and the difference in average rate between the sequences may not be obvious. On the other hand, the classical model of neofunctionalization predicts that the evolutionary rate in one of the two duplicates is accelerated. However, the classical model does not tell which of the duplicates experiences the acceleration in evolutionary rate. Here, we present evidence from the Saccharomyces cerevisiae genome that a duplicate located in a genomic region with a low-recombination rate is likely to evolve faster than a duplicate in an area of high recombination. This observation is consistent with population genetics theory that predicts that purifying selection is less effective in genomic regions of low recombination (Hill-Robertson effect). Together with previous studies, our results suggest the genomic background (e.g., local recombination rate) as a potential force to drive the divergence between nontandemly duplicated genes. This implies the importance of structure and complexity of genomes in the diversification of organisms via gene duplications.

scholarly journals Identification of residue inversions in large phylogenies of duplicated proteins

2021 ◽  
Author(s):  
Stefano Pascarelli ◽  
Paola Laurino
Keyword(s):  
Gene Duplication ◽  
Protein Sequence ◽  
Protein Function ◽  
High Throughput Sequencing ◽  
Functional Divergence ◽  
Growth Factor Receptor ◽  
Sequence Evolution ◽  
Protein Database ◽  
Sequencing Studies ◽  
Homology Relationship

Connecting protein sequence to function is becoming increasingly relevant since high-throughput sequencing studies accumulate large amounts of genomic data. Protein database annotation helps to bridge this gap; however, it is fundamental to understand the mechanisms underlying functional inheritance and divergence. If the homology relationship between proteins is known, can we determine whether the function diverged? In this work, we analyze different possibilities of protein sequence evolution after gene duplication and identify "residue inversions", i.e., sites where the relationship between the ancestry and the functional signal is decoupled. Residues in these sites play a role in functional divergence and could indicate a shift in protein function. We develop a method to recognize residue inversions in a phylogeny and test it on real and simulated datasets. In a dataset built from the Epidermal Growth Factor Receptor (EGFR) sequences found in 88 fish species, we identify 19 positions that went through inversion after gene duplication, mostly located at the ligand-binding extracellular domain.

scholarly journals Allele frequency divergence reveals ubiquitous influence of positive selection in Drosophila

2021 ◽  
Author(s):  
Jason Bertram
Keyword(s):  
Allele Frequency ◽  
Evolutionary Biology ◽  
Polymorphic Locus ◽  
Purifying Selection ◽  
Allele Frequencies ◽  
Intermediate Allele ◽  
Genome Wide ◽  
Signature Of Selection ◽  
Basic Objective ◽  
Genomic Regions

Resolving the role of natural selection is a basic objective of evolutionary biology. It is generally difficult to detect the influence of selection because ubiquitous non-selective stochastic change in allele frequencies (genetic drift) degrades evidence of selection. As a result, selection scans typically only identify genomic regions that have undergone episodes of intense selection. Yet it seems likely such episodes are the exception; the norm is more likely to involve subtle, concurrent selective changes at a large number of loci. We develop a new theoretical approach that uncovers a previously undocumented genome-wide signature of selection in the collective divergence of allele frequencies over time. Applying our approach to temporally-resolved allele frequency measurements from laboratory and wild Drosophila populations, we quantify the selective contribution to allele frequency divergence and find that selection has substantial effects on much of the genome. We further quantify the magnitude of the total selection coefficient (a measure of the combined effects of direct and linked selection) at a typical polymorphic locus, and find this to be large (of order 1%) even though most mutations are not directly under selection. We find that selective allele frequency divergence is substantial at intermediate allele frequencies, which we argue is most parsimoniously explained by positive --- not purifying --- selection. Thus, in these populations most mutations are far from evolving neutrally in the short term (tens of generations), including mutations with neutral fitness effects, and the result cannot be explained simply as a purging of deleterious mutations.

scholarly journals Conserved noncoding elements influence the transposable element landscape in Drosophila

2018 ◽  
Author(s):  
Manee M. Manee ◽  
John Jackson ◽  
Casey M. Bergman
Keyword(s):  
Transposable Element ◽  
Significant Proportion ◽  
Purifying Selection ◽  
Noncoding Dna ◽  
Frequency Spectra ◽  
Noncoding Regions ◽  
Selective Constraints ◽  
Large Numbers ◽  
Random Expectation ◽  
Conserved Noncoding Elements

AbstractHighly conserved noncoding elements (CNEs) comprise a significant proportion of the genomes of multicellular eukaryotes. The function of most CNEs remains elusive, but growing evidence indicates they are under some form of purifying selection. Noncoding regions in many species also harbor large numbers of transposable element (TE) insertions, which are typically lineage specific and depleted in exons because of their deleterious effects on gene function or expression. However, it is currently unknown whether the landscape of TE insertions in noncoding regions is random or influenced by purifying selection on CNEs. Here we combine comparative and population genomic data in Drosophila melanogaster to show that abundance of TE insertions in intronic and intergenic CNEs is reduced relative to random expectation, supporting the idea that selective constraints on CNEs eliminate a proportion of TE insertions in noncoding regions. However, we find no difference in the allele frequency spectra for polymorphic TE insertions in CNEs versus those in unconstrained spacer regions, suggesting that the distribution of fitness effects acting on observable TE insertions is similar across different functional compartments in noncoding DNA. Our results provide evidence that selective constraints on CNEs contribute to shaping the landscape of TE insertion in eukaryotic genomes, and provide further evidence supporting the conclusion that CNEs are indeed functionally constrained and not simply mutational cold spots.

Darwin’s molecule

Hemoglobin ◽  
2018 ◽  
pp. 201-232
Author(s):  
Jay F. Storz
Keyword(s):  
Protein Function ◽  
Evolutionary Biology ◽  
Lessons Learned ◽  
Atomic Resolution ◽  
Molecular Adaptation ◽  
Genetic Adaptation ◽  
Biochemical Phenotype ◽  
Causal Connections ◽  
Model Molecule ◽  
Model Protein

Chapter 9 discusses conceptual issues in protein evolution and provides a synthesis of lessons learned from studies of hemoglobin function. Using hemoglobin as a model molecule, we can exploit an unparalleled base of knowledge about structure-function relationships and we can characterize biophysical mechanisms of molecular adaptation at atomic resolution. It is therefore possible to document causal connections between genotype and biochemical phenotype at an unsurpassed level of rigor and detail. Moreover, since the oxygenation properties of hemoglobin provide a direct link between ambient O2 availability and aerobic metabolism, genetically based changes in protein function can be related to ecologically relevant aspects of organismal physiology. We therefore have a solid theoretical framework for making predictions and for interpreting observed associations between biochemical phenotype and fitness-related measures of whole-animal physiological performance. The chapter explores case studies that illustrate how experimental research on functional properties of a well-chosen model protein can be used to address some of the most conceptually expansive questions in evolutionary biology: Is genetic adaptation predictable? Why does evolution follow some pathways rather than others?

scholarly journals Generalizing rate heterogeneity across sites in statistical phylogenetics

2020 ◽  
Vol 20 (4) ◽  
pp. 410-436
Author(s):  
Sarah E Heaps ◽  
Tom MW Nye ◽  
Richard J Boys ◽  
Tom A Williams ◽  
Svetlana Cherlin ◽  
...  
Keyword(s):  
Linear Models ◽  
Sequence Data ◽  
Sequence Evolution ◽  
Rate Matrix ◽  
Molecular Sequence Data ◽  
Instantaneous Rate ◽  
Sequence Composition ◽  
Molecular Sequence ◽  
Selective Constraints ◽  
Posterior Inference

Phylogenetics uses alignments of molecular sequence data to learn about evolutionary trees relating species. Along branches, sequence evolution is modelled using a continuous-time Markov process characterized by an instantaneous rate matrix. Early models assumed the same rate matrix governed substitutions at all sites of the alignment, ignoring variation in evolutionary pressures. Substantial improvements in phylogenetic inference and model fit were achieved by augmenting these models with multiplicative random effects that describe the result of variation in selective constraints and allow sites to evolve at different rates which linearly scale a baseline rate matrix. Motivated by this pioneering work, we consider an extension using a quadratic, rather than linear, transformation. The resulting models allow for variation in the selective coefficients of different types of point mutation at a site in addition to variation in selective constraints. We derive properties of the extended models. For certain non-stationary processes, the extension gives a model that allows variation in sequence composition, both across sites and taxa. We adopt a Bayesian approach, describe an MCMC algorithm for posterior inference and provide software. Our quadratic models are applied to alignments spanning the tree of life and compared with site-homogeneous and linear models.

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