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25 results for “amino acid substitution”
An unusual amino acid substitution within hummingbird cytochrome c oxidase alters a key proton-conducting channel
<p>Hummingbirds in flight exhibit the highest metabolic rate of all vertebrates. The bioenergetic requirements associated with sustained hovering flight raise the possibility of unique amino acid substitutions that would enhance aerobic metabolism. Here, we have identified a non-conservative substitution within the mitochondria-encoded cytochrome <i>c</i> oxidase subunit I (COI) that is fixed within hummingbirds, yet exceedingly rare among other vertebrates. This unusual change is also rare among metazoans, but can be identified in several clades with diverse life histories. We performed atomistic molecular dynamics simulations using bovine and hummingbird COI models, thereby bypassing experimental limitations imposed by the inability to modify mtDNA in a site-specific manner. Intriguingly, our findings suggest that COI amino acid position 153 (bovine numbering system) provides control over the hydration and activity of a key proton channel in COX. We discuss potential phenotypic outcomes linked to this intriguing alteration encoded by the hummingbird mitochondrial genome.</p>
Data for: Epistatic effects between amino acid insertions and substitutions mediate toxin-resistance of vertebrate Na+, K+-ATPases
<p>The recurrent evolution of resistance to cardiotonic steroids (CTS) across diverse animals most frequently involves convergent amino-acid substitutions in the H1-H2 extracellular loop of Na<sub>+</sub>, K<sub>+</sub>-ATPase (NKA). Previous work revealed that hystricognath rodents (e.g. chinchilla) and pterocliform birds (sandgrouse) have convergently evolved amino-acid insertions in the H1-H2 loop, but their functional significance was not known. Using protein engineering, we show that these insertions have distinct effects on CTS resistance in homologs of each of the two species that strongly depend on intramolecular interactions with other residues. Removing the insertion in the chinchilla NKA unexpectedly increases CTS resistance and decreases NKA activity. In the sandgrouse NKA, the amino acid insertion and substitution Q111R both contribute to an augmented CTS resistance without compromising ATPase activity levels. Molecular docking simulations provide additional insight into the biophysical mechanisms responsible for the context-specific mutational effects on CTS insensitivity of the enzyme. Our results highlight the diversity of genetic substrates that underlie CTS insensitivity in vertebrate NKA and reveal how amino-acid insertions can alter the phenotypic effects of point mutations at key sites in the same protein domain.</p>
Data for: Epistatic effects between amino acid insertions and substitutions mediate toxin-resistance of vertebrate Na+, K+-ATPases
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Data from: Concerted evolution reveals co-adapted amino acid substitutions in Na+K+ ATPase of frogs that prey on toxic toads
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An unusual amino acid substitution within hummingbird cytochrome c oxidase alters a key proton-conducting channel
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Data for: Torii et al., Influence of amino acid substitutions in capsid proteins of coxsackievirus B5 on free chlorine and thermal inactivation
<p>This folder contains the experimental data for the figures shown in the main manuscript.</p>
Supplementary material for: nQMaker: estimating time non-reversible amino acid substitution models
<p><span>Amino acid substitution models are a key component in phylogenetic analyses of protein sequences. All commonly-used amino acid models available to date are time-reversible, an assumption designed for computational convenience but not for biological reality. Another significant downside to time-reversible models is that they do not allow inference of rooted trees without outgroups. In this paper, we introduce a maximum likelihood approach nQMaker, an extension of the recently published QMaker method, that allows the estimation of time non-reversible amino acid substitution models and rooted phylogenetic trees from a set of protein sequence alignments. We show that the non-reversible models estimated with nQMaker are a much better fit to empirical alignments than pre-existing reversible models, across a wide range of datasets including mammals, birds, plants, fungi, and other taxa, and that the improvements in model fit scale with the size of the dataset. Notably, for the recently published plant and bird trees, these non-reversible models correctly recovered the commonly estimated root placements with very high statistical support without the need to use an outgroup. We provide nQMaker as an easy-to-use feature in the IQ-TREE software (<a href="http://www.iqtree.org">http://www.iqtree.org</a>), allowing users to estimate non-reversible models and rooted phylogenies from their own protein datasets.</span></p>
Parthenogenesis doubles the rate of amino acid substitution in Whiptail mitochondria
<p class="MsoNormal"><span>Sexual reproduction is ubiquitous in the natural world, suggesting that sex must have extensive benefits to overcome the cost of males compared to asexual reproduction. One hypothesized advantage of sex with strong theoretical support is that sex plays a role in removing deleterious mutations from the genome. Theory predicts that transitions to asexuality should lead to the suppression of recombination and segregation and, in turn, weakened natural selection, allowing for the accumulation of slightly deleterious mutations. We tested this prediction by estimating the d<em>N</em>/d<em>S</em> ratios in asexual vertebrate lineages in the genus <em>Aspidoscelis</em> using whole mitochondrial genomes from seven asexual and five sexual species. We found higher d<em>N</em>/d<em>S</em> ratios in asexual <em>Aspidoscelis </em>species, indicating that asexual whiptails accumulate non-synonymous substitutions due to weaker purifying selection. Additionally, we estimated nucleotide diversity and found that asexuals harbor significantly less diversity. Thus, despite their recent origins, slightly deleterious mutations accumulated rapidly enough in asexual lineages to be detected. We provided empirical evidence to corroborate the connection between asexuality and increased </span><span>amino acid substitutions</span><span> in asexual vertebrate lineages.</span></p> <p class="MsoNormal"><span> </span></p>
Supplementary material for: nQMaker: estimating time non-reversible amino acid substitution models
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Parthenogenesis doubles the rate of amino acid substitution in Whiptail mitochondria
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Data from: Creation of photocyclic vertebrate rhodopsin by single amino acid substitution
<p><span>Opsins are universal photoreceptive proteins in animals and can be classified into three types based on their photoreaction properties. Upon light irradiation, vertebrate rhodopsin forms a metastable active state, which cannot revert back to the original dark state via either photoreaction or thermal reaction. By contrast, after photoreception, most opsins form a stable active state which can photo-convert back to the dark state. Moreover, we recently found a novel type of opsins whose activity is regulated by photocycling. However, the molecular mechanism underlying this diversification of opsins remains unknown. In this study, we showed that</span><span> vertebrate rhodopsin acquired the photocyclic and photoreversible properties upon introduction of a single mutation at position 188. This revealed that the residue at position 188 contributes to the diversification of photoreaction properties of opsins by its regulation of the recovery from the active state to the original dark state.</span></p>
Data from: Sequence entropy of folding and the absolute rate of amino acid substitutions
Adequate representations of protein evolution should consider how the acceptance of mutations depends on the sequence context in which they arise. However, epistatic interactions among sites in a protein result in hererogeneities in the substitution rate, both temporal and spatial, that are beyond the capabilities of current models. Here we use parallels between amino acid substitutions and chemical reaction kinetics to develop an improved theory of protein evolution. We constructed a mechanistic framework for modelling amino acid substitution rates that uses the formalisms of statistical mechanics, with principles of population genetics underlying the analysis. Theoretical analyses and computer simulations of proteins under purifying selection for thermodynamic stability show that substitution rates and the stabilization of resident amino acids (the 'evolutionary Stokes shift') can be predicted from biophysics and the effect of sequence entropy alone. Furthermore, we demonstrate that substitutions predominantly occur when epistatic interactions result in near neutrality; substitution rates are determined by how often epistasis results in such nearly neutral conditions. This theory provides a general framework for modelling protein sequence change under purifying selection, potentially explains patterns of convergence and mutation rates in real proteins that are incompatible with previous models, and provides a better null model for the detection of adaptive changes.
Evaluation of Phe Fluctuation in PKU Pts Treated With PKU GOLIKE Versus Standard Amino Acid Protein Substitute.
ClinicalTrials.gov study NCT05487378. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Data from: Sequence entropy of folding and the absolute rate of amino acid substitutions
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Data from: Creation of photocyclic vertebrate rhodopsin by single amino acid substitution
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Data from: ModelOMatic: fast and automated comparison between RY, nucleotide, amino acid, and codon substitution models
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Sperm chromatin structure and reproductive fitness are altered by substitution of a single amino acid in mouse Protamine 1
GEO Series GSE225271. Mus musculus. 54 samples. Type: Expression profiling by high throughput sequencing; Methylation profiling by high throughput sequencing.
A single amino acid substitution in the capsid protein of Zika virus contributes to the African lineage-specific virulence phenotypes
GEO Series GSE226495. Mus musculus. 9 samples. Type: Expression profiling by high throughput sequencing.
A Single Amino-Acid Substitution of RNA Polymerase ß subunit Confers A Novel Class of VISA phenotype on hVISA Strain Mu3
GEO Series GSE50826. Staphylococcus aureus. 5 samples. Type: Expression profiling by array.
ARTEMIS DIANE T790M (An Amino Acid Substitution at Position 790 in EGFR, From a Threonine (T) to a Methionine (M)) Mutation at Hospital Laboratories in Comparison With Central Laboratory
ClinicalTrials.gov study NCT02991274. IPD Sharing: Not stated. Countries: 1. Publications: 0.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.