scholarly journals An Integrated Model of Phenotypic Trait Changes and Site-Specific Sequence Evolution

2017 ◽  
Vol 66 (6) ◽  
pp. 917-933 ◽  
Author(s):  
Eli Levy Karin ◽  
Susann Wicke ◽  
Tal Pupko ◽  
Itay Mayrose
Keyword(s):  
Integrated Model ◽  
Phenotypic Trait ◽  
Sequence Evolution ◽  
Specific Sequence ◽  
Site Specific

scholarly journals Mitonuclear Coevolution, but Not Nuclear Compensation, Drives Evolution of OXPHOS Complexes in Bivalves

2021 ◽  
Author(s):  
Giovanni Piccinini ◽  
Mariangela Iannello ◽  
Guglielmo Puccio ◽  
Federico Plazzi ◽  
Justin C Havird ◽  
...  
Keyword(s):  
Specific Form ◽  
Nuclear Genes ◽  
Sequence Evolution ◽  
Bivalve Species ◽  
Mitochondrial Mutations ◽  
Site Specific ◽  
Mtdna Inheritance ◽  
Highly Correlated ◽  
Compensation Hypothesis ◽  
Mtdna Variability

Abstract In Metazoa, 4 out of 5 complexes involved in oxidative phosphorylation (OXPHOS) are formed by subunits encoded by both the mitochondrial (mtDNA) and nuclear (nuDNA) genomes, leading to the expectation of mito-nuclear coevolution. Previous studies have supported co-adaptation of mitochondria-encoded (mtOXPHOS) and nuclear-encoded OXPHOS (nuOXPHOS) subunits, often specifically interpreted with regard to the “nuclear compensation hypothesis”, a specific form of mitonuclear coevolution where nuclear genes compensate for deleterious mitochondrial mutations owing to less efficient mitochondrial selection. In this study we analysed patterns of sequence evolution of 79 OXPHOS subunits in 31 bivalve species, a taxon showing extraordinary mtDNA variability and including species with “doubly uniparental” mtDNA inheritance. Our data showed strong and clear signals of mitonuclear coevolution. NuOXPHOS subunits had concordant topologies with mtOXPHOS subunits, contrary to previous phylogenies based on nuclear genes lacking mt interactions. Evolutionary rates between mt and nuOXPHOS subunits were also highly correlated compared to non-OXPHOS-interacting nuclear genes. Nuclear subunits of chimeric OXPHOS complexes (I, III, IV, and V) also had higher dN/dS ratios than Complex II, which is formed exclusively by nuDNA-encoded subunits. However, we did not find evidence of nuclear compensation: mitochondria-encoded subunits showed similar dN/dS ratios compared to nuclear-encoded subunits, contrary to most previously studied bilaterian animals. Moreover, no site-specific signals of compensatory positive selection were detected in nuOXPHOS genes. Our analyses extend the evidence for mitonuclear coevolution to a new taxonomic group, but we propose a reconsideration of the nuclear compensation hypothesis.

Amino-Functionalized 5′ Cap Analogs as Tools for Site-Specific Sequence-Independent Labeling of mRNA

2017 ◽  
Vol 28 (7) ◽  
pp. 1978-1992 ◽  
Author(s):  
Marcin Warminski ◽  
Pawel J. Sikorski ◽  
Zofia Warminska ◽  
Maciej Lukaszewicz ◽  
Anna Kropiwnicka ◽  
...  
Keyword(s):  
Specific Sequence ◽  
Site Specific

scholarly journals Deconvolving nuclesome binding energy from experimental errors

2020 ◽  
Author(s):  
Mark Heron ◽  
Johannes Soeding
Keyword(s):  
Transcription Factors ◽  
Integrated Model ◽  
Specific Pattern ◽  
Quantitative Prediction ◽  
Specific Sequence ◽  
Sequence Preference ◽  
Open Questions ◽  
Binding Preference ◽  
Experimental Errors ◽  
Nucleosome Binding

1AbstractEukaryotic genomes are compacted into nucleosomes, 147-bp of DNA wrapped around histone proteins. Nucleosomes can hinder transcription factors and other DNA-binding proteins from accessing the genome. This competition at promoters and enhancers regulates gene expression. Therefore, a quantitative understanding of gene regulation requires the quantitative prediction of nucleosome binding affinities. However, little is known for certain about the sequence preference of nucleosomes.Here we develop an integrated model of nucleosome binding and genome-wide measurements thereof. Our model learns similar nucleosome sequence preferences from MNase-Seq and CC-Seq datasets.We find that modelling the positional uncertainty of MNase-Seq deconvolves the commonly described smooth 10-bp-periodic sequence preference into a position-specific pattern more closely resembling the pattern obtained from high-resolution CC-Seq data. By analysing the CC-Seq data we reveal the strong preference of A/T at +/− 3 bp from the dyad as an experimental bias. Our integrated model can separate this bias of CC-Seq from the true nucleosome binding preference.Our results show that nucleosomes have position-specific sequence preferences, which probably play an important role in their competition with transcription factors. Furthermore, our comparison of diverse datasets shows that the experimental biases have a similar strength as the signal of nucleosome-positioning measurements. Validating nucleosome models on experiments with similar biases overestimates their prediction quality of the true nucleosome binding.There are still many open questions about the sequence preference of nucleosomes and our approach will need to be extended to answer them. Only integrated models that combine the thermodynamics of nucleosome binding with experimental errors can deconvolve the two and learn the true preferences of nucleosomes.

CLUSTERING OF CALIBRATED RADIOCARBON DATES: SITE-SPECIFIC CHRONOLOGICAL SEQUENCES IDENTIFIED BY DENSE RADIOCARBON SAMPLING

Radiocarbon ◽  
2020 ◽  
pp. 1-10
Author(s):  
Peter Demján ◽  
Peter Pavúk
Keyword(s):  
Bronze Age ◽  
Statistical Significance ◽  
Real Life ◽  
Simulated Data ◽  
Hierarchical Cluster ◽  
Specific Sequence ◽  
Radiocarbon Dates ◽  
Site Specific ◽  
Archaeological Data ◽  
A Site

ABSTRACT Calibrated radiocarbon (14C) determinations are commonly used in archaeology to assign calendar dates to a site’s chronological phases identified based on additional evidence such as stratigraphy. In the absence of such evidence, we can perform dense 14C sampling of the site to attempt to identify periods of heightened activity, separated by periods of inactivity, which correspond to archaeological phases and gaps between them. We propose a method to achieve this by hierarchical cluster analysis of the calibrated 14C dates, followed by testing of the different clustering solutions for consistency based on silhouette coefficient and statistical significance using randomization. Separate events identified in such a way can then be regarded as evidence for distinct phases of activity and used to construct a site-specific sequence. This can be in turn used as a Bayesian prior to further narrow down the distributions of the calibrated 14C dates. We assessed the validity of the method using simulated data as well as real-life archaeological data from the Bronze Age settlement of Troy. A Python implementation of the method is available online at https://github.com/demjanp/clustering_14C.

scholarly journals Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites

2014 ◽  
Author(s):  
Julian Echave ◽  
Eleisha L. Jackson ◽  
Claus O. Wilke
Keyword(s):  
Evolutionary Rate ◽  
Biophysical Model ◽  
Rate Variation ◽  
Sequence Evolution ◽  
Stress Model ◽  
Specific Sequence ◽  
Active Structure ◽  
Stability Model ◽  
The Stability ◽  
The Relationship

AbstractEvolutionary-rate variation among sites within proteins depends on functional and biophysical properties that constrain protein evolution. It is generally accepted that proteins must be able to fold stably in order to function. However, the relationship between stability constraints and among-sites rate variation is not well understood. Here, we present a biophysical model that links the thermodynamic stability changes due to mutations at sites in proteins (ΔΔG) to the rate at which mutations accumulate at those sites over evolutionary time. We find that such a “stability model” generally performs well, displaying correlations between predicted and empirically observed rates of up to 0.75 for some proteins. We further find that our model has comparable predictive power as does an alternative, recently proposed “stress model” that explains evolutionary-rate variation among sites in terms of the excess energy needed for mutants to adopt the correct active structure (ΔΔG*). The two models make distinct predictions, though, and for some proteins the stability model outperforms the stress model and vice versa. We conclude that both stability and stress constrain site-specific sequence evolution in proteins.

scholarly journals Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
David A Rasmussen ◽  
Tanja Stadler
Keyword(s):  
Population Level ◽  
Character State ◽  
Sequence Evolution ◽  
Deleterious Mutations ◽  
Site Specific ◽  
Fitness Effects ◽  
Single Character ◽  
Phylogenetic Models ◽  
Birth Death

Beneficial and deleterious mutations cause the fitness of lineages to vary across a phylogeny and thereby shape its branching structure. While standard phylogenetic models do not allow mutations to feedback and shape trees, birth-death models can account for this feedback by letting the fitness of lineages depend on their type. To date, these multi-type birth-death models have only been applied to cases where a lineage’s fitness is determined by a single character state. We extend these models to track sequence evolution at multiple sites. This approach remains computationally tractable by tracking the genotype and fitness of lineages probabilistically in an approximate manner. Although approximate, we show that we can accurately estimate the fitness of lineages and site-specific mutational fitness effects from phylogenies. We apply this approach to estimate the population-level fitness effects of mutations in Ebola and influenza virus, and compare our estimates with in vitro fitness measurements for these mutations.

Molecular origins of folding rate differences in the thioredoxin family

2020 ◽  
Vol 477 (6) ◽  
pp. 1083-1087 ◽  
Author(s):  
Athi N. Naganathan
Keyword(s):  
Protein Design ◽  
Redox Balance ◽  
Model Systems ◽  
Sequence Evolution ◽  
Specific Sequence ◽  
Folding Rate ◽  
Folding Rates ◽  
Reconstruction Methods ◽  
Sequence Reconstruction ◽  
Selected Subset

Thioredoxins are a family of conserved oxidoreductases responsible for maintaining redox balance within cells. They have also served as excellent model systems for protein design and engineering studies particularly through ancestral sequence reconstruction methods. The recent work by Gamiz-Arco et al. [Biochem J (2019) 476, 3631–3647] answers fundamental questions on how specific sequence differences can contribute to differences in folding rates between modern and ancient thioredoxins but also among a selected subset of modern thioredoxins. They surprisingly find that rapid unassisted folding, a feature of ancient thioredoxins, is not conserved in the modern descendants suggestive of co-evolution of better folding machinery that likely enabled the accumulation of mutations that slow-down folding. The work thus provides an interesting take on the expected folding-stability-function constraint while arguing for additional factors that contribute to sequence evolution and hence impact folding efficiency.

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