scholarly journals Molecular Evolution of the Vertebrate FK506 Binding Protein 25

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Fei Liu ◽  
Xiao-Long Wei ◽  
Hao Li ◽  
Ji-Fu Wei ◽  
Yong-Qing Wang ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Nuclear Dna ◽  
Purifying Selection ◽  
Synonymous Substitution ◽  
Vertebrate Lineage ◽  
Gene Splicing ◽  
Fk506 Binding Protein ◽  
Ppiase Domain ◽  
Synonymous Substitution Rates ◽  
Peptidyl Prolyl Isomerases

FK506 binding proteins (FKBPs) belong to immunophilins with peptidyl-prolyl isomerases (PPIases) activity. FKBP25 (also known as FKBP3) is one of the nuclear DNA-binding proteins in the FKBPs family, which plays an important role in regulating transcription and chromatin structure. The calculation of nonsynonymous and synonymous substitution rates suggested that FKBP25 undergoes purifying selection throughout the whole vertebrate evolution. Moreover, the result of site-specific tests showed that no sites were detected under positive selection. Only one PPIase domain was detected by searching FKBP25 sequences at Pfam and SMART domain databases. Mammalian FKBP25 possess exon-intron conservation, although conservation in the whole vertebrate lineage is incomplete. The result of this study suggests that the purifying selection triggers FKBP25 evolutionary history, which allows us to discover the complete role of the PPIase domain in the interaction between FKBP25 and nuclear proteins. Moreover, intron alterations during FKBP25 evolution that regulate gene splicing may be involved in the purifying selection.

scholarly journals Genetic Diversity in the 3′ Terminal 4.7-kb Region of Grapevine leafroll-associated virus 3

2011 ◽  
Vol 101 (4) ◽  
pp. 445-450 ◽  
Author(s):  
Jinbo Wang ◽  
Abhineet M. Sharma ◽  
Siobain Duffy ◽  
Rodrigo P. P. Almeida
Keyword(s):  
Genetic Diversity ◽  
Purifying Selection ◽  
Synonymous Substitution ◽  
Effective Population ◽  
Data Set ◽  
Reading Frame ◽  
Napa Valley ◽  
Synonymous Substitution Rates ◽  
Leafroll Disease

Grapevine leafroll-associated virus 3 (GLRaV-3; Ampelovirus, Closteroviridae), associated with grapevine leafroll disease, is an important pathogen found across all major grape-growing regions of the world. The genetic diversity of GLRaV-3 in Napa Valley, CA, was studied by sequencing 4.7 kb in the 3′ terminal region of 50 isolates obtained from Vitis vinifera ‘Merlot’. GLRaV-3 isolates were subdivided into four distinct phylogenetic clades. No evidence of positive selection was observed in the data set, although neutral selection (ratio of nonsynonymous to synonymous substitution rates = 1.1) was observed in one open reading frame (ORF 11, p4). Additionally, the four clades had variable degrees of overall nucleotide diversity. Moreover, no geographical structure among isolates was observed, and isolates belonging to different phylogenetic clades were found in distinct vineyards, with one exception. Considered with the evidence of purifying selection (i.e., against deleterious mutations), these data indicate that the population of GLRaV-3 in Napa Valley is not expanding and its effective population size is not increasing. Furthermore, research on the biological characterization of GLRaV-3 strains might provide valuable insights on the biology of this species that may have epidemiological relevance.

scholarly journals Enhanced functional divergence of duplicate genes several million years after gene duplication in the Arabidopsis lineage

2016 ◽  
Author(s):  
Kousuke Hanada ◽  
Ayumi Tezuka ◽  
Masafumi Nozawa ◽  
Yutaka Suzuki ◽  
Sumio Sugano ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Functional Divergence ◽  
Purifying Selection ◽  
Orthologous Gene ◽  
Synonymous Substitution ◽  
Duplicate Genes ◽  
Duplicated Genes ◽  
Highly Qualified ◽  
Duplication Events ◽  
Synonymous Substitution Rates

AbstractLineage-specifically duplicated genes likely contribute to the phenotypic divergence in closely related species. However, neither the frequency of duplication events nor the degree of selective pressures immediately after gene duplication is clear in the speciation process. Plants have substantially higher gene duplication rates than most other eukaryotes. Here, using Illumina short reads from Arabidopsis halleri, which has highly qualified plant genomes in close species (Brassica rapa, A. thaliana and A. lyrata), we succeeded in generating orthologous gene groups among B. rapa, A. thaliana, A. lyrata and A. halleri. The frequency of duplication events in the Arabidopsis lineage was approximately 10 times higher than the frequency inferred by comparative genomics of Arabidopsis, poplar, rice and moss. Of the currently retained genes in A. halleri, 11–24% had undergone gene duplication in the Arabidopsis lineage. To examine the degree of selective pressure for duplicated genes, we calculated the ratios of nonsynonymous to synonymous substitution rates (KA/KS) in the A. halleri-lyrata and A. halleri lineages. Using a maximum-likelihood framework, we examined positive (KA/KS > 1) and purifying selection (KA/KS < 1) at a significant level (P < 0.01). Duplicate genes tended to have a higher proportion of positive selection compared with non-duplicated genes. More interestingly, we found that functional divergence of duplicated genes was accelerated several million years after gene duplication at a higher proportion than immediately after gene duplication.

scholarly journals A comparison of one-rate and two-rate inference frameworks for site-specific dN/dS estimation

2015 ◽  
Author(s):  
Stephanie J. Spielman ◽  
Suyang Wan ◽  
Claus O. Wilke
Keyword(s):  
Model Misspecification ◽  
Purifying Selection ◽  
Synonymous Substitution ◽  
Selective Constraint ◽  
Model Specification ◽  
Inference Model ◽  
Specific Context ◽  
Point Estimates ◽  
Synonymous Substitution Rates ◽  
Excessive Noise

AbstractTwo broad paradigms exist for inferring dN/dS, the ratio of nonsynonymous to synonymous substitution rates, from coding sequences: i) a one-rate approach, where dN/dS is represented with a single parameter, or ii) a two-rate approach, where dN and dS are estimated separately. The performances of these two approaches have been well-studied in the specific context of proper model specification, i.e. when the inference model matches the simulation model. By contrast, the relative performances of one-rate vs. two-rate parameterizations when applied to data generated according to a different mechanism remains unclear. Here, we compare the relative merits of one-rate and two-rate approaches in the specific context of model misspecification by simulating alignments with mutation-selection models rather than with dN/dS-based models. We find that one-rate frameworks generally infer more accurate dN/dS point estimates, even when dS varies among sites. In other words, modeling dS variation may substantially reduce accuracy of dN/dS point estimates. These results appear to depend on the selective constraint operating at a given site. In particular, for sites under strong purifying selection (dN/dS<~0.3), one-rate and two-rate models show comparable performances. However, one-rate models significantly outperform two-rate models for sites under moderate-to-weak purifying selection. We attribute this distinction to the fact that, for these more quickly evolving sites, a given substitution is more likely to be nonsynonymous than synonymous. The data will therefore be relatively enriched for nonsynonymous changes, and modeling dS contributes excessive noise to dN/dS estimates. We additionally find that high levels of divergence among sequences, rather than the number of sequences in the alignment, are more critical for obtaining precise point estimates.

scholarly journals SIX6 Shows High Divergence in Fusarium oxysporum f. sp. cubense TR4

2021 ◽  
Vol 25 (06) ◽  
pp. 1331-1338
Author(s):  
Nadya Farah
Keyword(s):  
Positive Selection ◽  
Fusarium Oxysporum ◽  
Purifying Selection ◽  
Synonymous Substitution ◽  
Effector Proteins ◽  
Pr Genes ◽  
Ratio Distribution ◽  
Formae Speciales ◽  
Pathogenesis Related ◽  
Synonymous Substitution Rates

Secreted fungal effector proteins and their host targets are good examples to understand the mechanism of host-pathogen co-evolution with genes involved in the interaction undergoing positive selection. SIX genes (secreted in xylem) are obtained via horizontal transfer and can be found within the formae speciales of Fusarium oxysporum. SIX6 and SIX9 of F. oxysporum f. spp. cubense (Foc) are predicted to play a role as effectors. However, their involvement in the pathogenicity of Foc in banana plants has not been determined yet. In the susceptible banana cultivar, we found that the SIX6 and SIX9 genes of Foc TR4 were highly expressed in roots, but not in corms or leaves. The host, however, expressed the pathogenesis-related (PR) genes, PR-1 and PR-3, in corms earlier than in the roots. Phylogenetic analysis on SIX6 and SIX9 genes of F. oxysporum has revealed the separation of SIX6 and SIX9 of Foc from other formae speciales. This leads to detecting genes under positive selection using the ratio nonsynonymous to synonymous substitution rates (Ka/Ks). SIX6 of Foc showed an increase in diversity, but insufficient to drive positive selection. Conversely, SIX9 of Foc showed no divergence in the dN/dS ratio distribution, indicating purifying selection. © 2021 Friends Science Publishers

Pseudogenized Amelogenin Reveals Early Tooth Loss in True Toads (Anura: Bufonidae)

2021 ◽  
Author(s):  
John Shaheen ◽  
Austin B Mudd ◽  
Thomas G H Diekwisch ◽  
John Abramyan
Keyword(s):  
Tooth Loss ◽  
Tooth Enamel ◽  
Synonymous Substitution ◽  
Bufo Bufo ◽  
Molecular Dating ◽  
Bufo Gargarizans ◽  
The Family ◽  
Synonymous Substitution Rates ◽  
Mandibular Teeth ◽  
Early Tooth Loss

Abstract Extant anurans (frogs and toads) exhibit reduced dentition, ranging from a lack of mandibular teeth to complete edentulation, as observed in the true toads of the family Bufonidae. The evolutionary timeline of these reductions remains vague due to a poor fossil record. Previous studies have demonstrated an association between the lack of teeth in edentulous vertebrates and the pseudogenization of the major tooth enamel gene amelogenin (AMEL) through accumulation of deleterious mutations and the disruption of its coding sequence. In the present study we have harnessed the pseudogenization of AMEL as a molecular dating tool to correlate loss of dentition with genomic mutation patterns during the rise of the family Bufonidae. Specifically, we have utilized AMEL pseudogenes in three members of the family as a tool to estimate the putative date of edentulation in true toads. Comparison of AMEL sequences from Rhinella marina, Bufo gargarizans and Bufo bufo, with nine extant, dentulous frogs, revealed mutations confirming AMEL inactivation in Bufonidae. AMEL pseudogenes in modern bufonids also exhibited remarkably high 86–93% sequence identity among each other, with only a slight increase in substitution rate and relaxation of selective pressure, in comparison to functional copies in other anurans. Moreover, using selection intensity estimates and synonymous substitution rates, analysis of functional and pseudogenized AMEL resulted in an estimated inactivation window of 46-60 MYA in the lineage leading to modern true toads, a timeline that coincides with the rise of the family Bufonidae.

scholarly journals Comparing Patterns of Nucleotide Substitution Rates Among Chloroplast Loci Using the Relative Ratio Test

Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 393-399 ◽  
Author(s):  
Spencer V Muse ◽  
Brandon S Gaut
Keyword(s):  
Nucleotide Substitution ◽  
Nonsynonymous Substitution ◽  
Synonymous Substitution ◽  
Joint Analysis ◽  
Ratio Test ◽  
Substitution Rates ◽  
Chloroplast Genomes ◽  
Synonymous Substitution Rates ◽  
Nucleotide Substitution Rates ◽  
Evolutionary Lineages

Even when several genetic loci are used in molecular evolutionary studies, each locus is typically analyzed independently of the others. This type of approach makes it difficult to study mechanisms and processes that affect multiple genes. In this work we develop a statistical approach for the joint analysis of two or more loci. The tests we propose examine whether or not nucleotide substitution rates across evolutionary lineages have the same relative proportions at two loci. Theses procedures are applied to 33 genes from the chloroplast genomes of rice, tobacco, pine, and liverwort. With the exception of five clearly distinct loci, we find that synonymous substitution rates tend to change proportionally across genes. We interpret these results to be consistent with a “lineage effect” acting on the entire chloroplast genome. In contrast, nonsynonymous rates do not change proportionally across genes, suggesting that locus-specific evolutionary effects dominate patterns of nonsynonymous substitution.

Synergistic action of interleukin-6 and glucocorticoids is mediated by the interleukin-6 response element of the rat alpha 2 macroglobulin gene

1992 ◽  
Vol 12 (5) ◽  
pp. 2282-2294
Author(s):  
G M Hocke ◽  
D Barry ◽  
G H Fey
Keyword(s):  
Dna Binding ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Binding Proteins ◽  
Nuclear Dna ◽  
Acute Phase Proteins ◽  
Dna Binding Proteins ◽  
Human Hepatoma Cells ◽  
Response Element ◽  
Multiple Copies

One class of genes coding for the acute-phase proteins (acute-phase genes) is induced by interleukin 6 (IL-6) through the human transcription factor NF-IL-6 and its rat homolog IL-6-DBP/LAP. A second class, represented by the rat alpha 2 macroglobulin gene, utilizes a different IL-6 response element (IL-6-RE) and different DNA-binding proteins interacting with this element, the so-called IL-6-RE binding proteins (IL-6 RE-BPs). Human Hep3B and HepG2 hepatoma, U266 myeloma, and CESS lymphoblastoid cells contain IL-6 RE-BPs that form complexes, with the IL-6-RE, with gel mobilities indistinguishable from those of the corresponding complexes of rat liver cells. The ability to form these complexes was induced by IL-6 in human hepatoma cells with a maximum reached after 4 h and required ongoing protein synthesis. Multiple copies of an 18-bp element containing the IL-6-RE core were sufficient to confer both induction by IL-6 and a synergistic induction by IL-6 plus glucocorticoids to minimal promoters. The synergism was blocked by the receptor antagonist RU486 and thus was dependent on the glucocorticoid receptor (GR). However, the 18-bp element contained no consensus GR-binding site, and recombinant GR did not bind at this sequence. Therefore, the synergism was probably achieved by an indirect effect of a glucocorticoid-activated intermediate gene on the IL-6 RE-BPs. The rat IL-6 RE-BP had a molecular weight of 102 +/- 10 kDa and was thus distinct from NF-IL-6 and IL-6-DBP/LAP. Therefore, IL-6 must activate two different classes of liver acute-phase genes through at least two different nuclear DNA-binding proteins: NF-IL-6/IL-6-DBP/LAP and the IL-6 RE-BP.

scholarly journals Matrin3: Disorder and ALS Pathogenesis

2022 ◽  
Vol 8 ◽  
Author(s):  
Ahmed Salem ◽  
Carter J. Wilson ◽  
Benjamin S. Rutledge ◽  
Allison Dilliott ◽  
Sali Farhan ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Binding Proteins ◽  
Rna Binding ◽  
Nuclear Dna ◽  
Neurodegenerative Disorder ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons in the brain and spinal cord. ALS is associated with protein misfolding and inclusion formation involving RNA-binding proteins, including TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS). The 125-kDa Matrin3 is a highly conserved nuclear DNA/RNA-binding protein that is implicated in many cellular processes, including binding and stabilizing mRNA, regulating mRNA nuclear export, modulating alternative splicing, and managing chromosomal distribution. Mutations in MATR3, the gene encoding Matrin3, have been identified as causal in familial ALS (fALS). Matrin3 lacks a prion-like domain that characterizes many other ALS-associated RNA-binding proteins, including TDP-43 and FUS, however, our bioinformatics analyses and preliminary studies document that Matrin3 contains long intrinsically disordered regions that may facilitate promiscuous interactions with many proteins and may contribute to its misfolding. In addition, these disordered regions in Matrin3 undergo numerous post-translational modifications, including phosphorylation, ubiquitination and acetylation that modulate the function and misfolding of the protein. Here we discuss the disordered nature of Matrin3 and review the factors that may promote its misfolding and aggregation, two elements that might explain its role in ALS pathogenesis.

scholarly journals Eusociality Shapes Convergent Patterns of Molecular Evolution across Mitochondrial Genomes of Snapping Shrimps

2020 ◽  
Author(s):  
Solomon T C Chak ◽  
Juan Antonio Baeza ◽  
Phillip Barden
Keyword(s):  
Molecular Evolution ◽  
Genome Evolution ◽  
Purifying Selection ◽  
Synonymous Substitution ◽  
Mitochondrial Genomes ◽  
Comparative Genomic ◽  
Effective Population ◽  
Protein Coding ◽  
Marine Realm ◽  
Snapping Shrimps

Abstract Eusociality is a highly conspicuous and ecologically impactful behavioral syndrome that has evolved independently across multiple animal lineages. So far, comparative genomic analyses of advanced sociality have been mostly limited to insects. Here, we study the only clade of animals known to exhibit eusociality in the marine realm—lineages of socially diverse snapping shrimps in the genus Synalpheus. To investigate the molecular impact of sociality, we assembled the mitochondrial genomes of eight Synalpheus species that represent three independent origins of eusociality and analyzed patterns of molecular evolution in protein-coding genes. Synonymous substitution rates are lower and potential signals of relaxed purifying selection are higher in eusocial relative to noneusocial taxa. Our results suggest that mitochondrial genome evolution was shaped by eusociality-linked traits—extended generation times and reduced effective population sizes that are hallmarks of advanced animal societies. This is the first direct evidence of eusociality impacting genome evolution in marine taxa. Our results also strongly support the idea that eusociality can shape genome evolution through profound changes in life history and demography.

scholarly journals Characterization of hypoxia-responsive enhancer in the human erythropoietin gene shows presence of hypoxia-inducible 120-Kd nuclear DNA-binding protein in erythropoietin-producing and nonproducing cells

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 704-711 ◽  
Author(s):  
I Beck ◽  
R Weinmann ◽  
J Caro
Keyword(s):  
Protein Synthesis ◽  
Dna Binding ◽  
Binding Proteins ◽  
Nuclear Dna ◽  
Dna Binding Proteins ◽  
Protein Synthesis Inhibitor ◽  
Activation Process ◽  
Enhancer Element ◽  
Flanking Region

Abstract Erythropoietin (Epo) production in response to hypoxia or cobalt is primarily mediated by activation of transcription of the Epo gene. Recently an hypoxia responsive enhancer was identified in the 3′ flanking region of the mouse and human Epo genes. Using functional analysis in Hep 3B cells we define here the minimal enhancer element as a 29-bp segment starting at the Apa1 site in the 3′ flanking region of the human Epo gene. Mutagenesis studies of the minimal element identified three different areas that are necessary for full enhancer activity. Electrophoretic mobility shift assays show the presence of hypoxia- and/or cobalt-inducible nuclear DNA-binding proteins that bind to one of the active sites of the enhancer. Induction of hypoxia- binding activity was abolished by Anisomycin, a potent protein synthesis inhibitor, suggesting that de novo protein synthesis is necessary for the activation process. Further characterization of DNA- binding proteins by use of UV light crosslinking identified a protein of molecular weight of approximately 120-Kd that was present only in hypoxic extracts. This protein was found to be present in hypoxic nuclear extracts from both Epo-producing and non-Epo-producing cells, suggesting that it may be involved in a more generalized mechanism of cellular response to hypoxia.

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