scholarly journals Non-neutral evolution of H3.3-encoding genes occurs without alterations in protein sequence

2018 ◽  
Author(s):  
Brejnev M. Muhire ◽  
Matthew A. Booker ◽  
Michael Y. Tolstorukov
Keyword(s):  
Codon Usage ◽  
Purifying Selection ◽  
Fine Tuning ◽  
Gene Arrangement ◽  
Neutral Evolution ◽  
Evolutionarily Conserved ◽  
Induced Genes ◽  
And Function ◽  
Evolutionary Paths ◽  
Encoding Genes

AbstractHistone H3.3 is a developmentally essential variant encoded by two independent genes in human (H3F3A and H3F3B). While this two-gene arrangement is evolutionarily conserved, its origins and function remain unknown. Phylogenetics, synteny and gene structure analyses of the H3.3 genes from 32 metazoan genomes indicate independent evolutionary paths for H3F3A and H3F3B. While H3F3B bears similarities with H3.3 genes in distant organisms and with canonical H3 genes, H3F3A is sarcopterygian-specific and evolves under strong purifying selection. Additionally, H3F3B codon-usage preferences resemble those of broadly expressed genes and ‘cell differentiation-induced’ genes, while codon-usage of H3F3A resembles that of ‘cell proliferation-induced’ genes. We infer that H3F3B is more similar to the ancestral H3.3 gene and likely evolutionarily adapted for broad expression pattern in diverse cellular programs, while H3F3A adapted for a subset of gene expression programs. Thus, the arrangement of two independent H3.3 genes facilitates fine-tuning of H3.3 expression across cellular programs.

scholarly journals Identification and Functional Analysis of Apoptotic Protease Activating Factor-1 (Apaf-1) from Spodoptera litura

Insects ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 64
Author(s):  
Haihao Ma ◽  
Xiumei Yan ◽  
Lin Yan ◽  
Jingyan Zhao ◽  
Jiping Song ◽  
...  
Keyword(s):  
Spodoptera Litura ◽  
Actinomycin D ◽  
Titration Calorimetry ◽  
Apoptosis Pathway ◽  
Downstream Effector ◽  
Lepidopteran Insects ◽  
Evolutionarily Conserved ◽  
Effector Caspases ◽  
And Function

Apoptotic protease activating factor-1 (Apaf-1) is an adaptor molecule, essential for activating initiator caspase and downstream effector caspases, which directly cause apoptosis. In fruit flies, nematodes, and mammals, Apaf-1 has been extensively studied. However, the structure and function of Apaf-1 in Lepidoptera remain unclear. This study identified a novel Apaf-1 from Spodoptera litura, named Sl-Apaf-1. Sl-Apaf-1 contains three domains: a CARD domain, as well as NOD and WD motifs, and is very similar to mammalian Apaf-1. Interference of Sl-apaf-1 expression in SL-1 cells blocked apoptosis induced by actinomycin D. Overexpression of Sl-apaf-1 significantly enhances apoptosis induced by actinomycin D in Sf9/SL-1/U2OS cells, suggesting that the function of Sl-Apaf-1 is evolutionarily conserved. Furthermore, Sl-Apaf-1 could interact with Sl-caspase-5 (a homologue of mammalian caspase-9) and yielded a binding affinity of 1.37 × 106 M–1 according isothermal titration calorimetry assay. Initiator caspase (procaspase-5) of S. litura could be activated by Sl-Apaf-1 (without WD motif) in vitro, and the activated Sl-caspase-5 could cleave Sl-procaspase-1 (a homologue of caspase-3 in mammals), which directly caused apoptosis. This study demonstrates the key role of Sl-Apaf-1 in the apoptosis pathway, suggesting that the apoptosis pathway in Lepidopteran insects and mammals is conserved.

scholarly journals Codon harmonization reduces amino acid misincorporation in bacterially expressed P. falciparum proteins and improves their immunogenicity

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Neeraja Punde ◽  
Jennifer Kooken ◽  
Dagmar Leary ◽  
Patricia M. Legler ◽  
Evelina Angov
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Codon Usage ◽  
Dna Sequences ◽  
Structural Integrity ◽  
Host Cells ◽  
Loss Of Function ◽  
Species Specific ◽  
And Function ◽  
The Impact

Abstract Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage. “Codon harmonization” more closely aligns native codon usage frequencies with those of the expression host particularly within putative inter-domain segments where slower rates of translation may play a role in protein folding. Heterologous expression of Plasmodium falciparum genes in Escherichia coli has been a challenge due to their AT-rich codon bias and the highly repetitive DNA sequences. Here, codon harmonization was applied to the malarial antigen, CelTOS (Cell-traversal protein for ookinetes and sporozoites). CelTOS is a highly conserved P. falciparum protein involved in cellular traversal through mosquito and vertebrate host cells. It reversibly refolds after thermal denaturation making it a desirable malarial vaccine candidate. Protein expressed in E. coli from a codon harmonized sequence of P. falciparum CelTOS (CH-PfCelTOS) was compared with protein expressed from the native codon sequence (N-PfCelTOS) to assess the impact of codon usage on protein expression levels, solubility, yield, stability, structural integrity, recognition with CelTOS-specific mAbs and immunogenicity in mice. While the translated proteins were expected to be identical, the translated products produced from the codon-harmonized sequence differed in helical content and showed a smaller distribution of polypeptides in mass spectra indicating lower heterogeneity of the codon harmonized version and fewer amino acid misincorporations. Substitutions of hydrophobic-to-hydrophobic amino acid were observed more commonly than any other. CH-PfCelTOS induced significantly higher antibody levels compared with N-PfCelTOS; however, no significant differences in either IFN-γ or IL-4 cellular responses were detected between the two antigens.

scholarly journals Endothelium as a Source and Target of H2S to Improve Its Trophism and Function

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 486
Author(s):  
Valerio Ciccone ◽  
Shirley Genah ◽  
Lucia Morbidelli
Keyword(s):  
Endothelial Dysfunction ◽  
Vessel Wall ◽  
Redox Reactions ◽  
Single Layer ◽  
Fine Tuning ◽  
Therapeutic Approaches ◽  
Impaired Wound Healing ◽  
Blood Fluidity ◽  
And Function ◽  
And Control

The vascular endothelium consists of a single layer of squamous endothelial cells (ECs) lining the inner surface of blood vessels. Nowadays, it is no longer considered as a simple barrier between the blood and vessel wall, but a central hub to control blood flow homeostasis and fulfill tissue metabolic demands by furnishing oxygen and nutrients. The endothelium regulates the proper functioning of vessels and microcirculation, in terms of tone control, blood fluidity, and fine tuning of inflammatory and redox reactions within the vessel wall and in surrounding tissues. This multiplicity of effects is due to the ability of ECs to produce, process, and release key modulators. Among these, gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H2S) are very active molecules constitutively produced by endotheliocytes for the maintenance and control of vascular physiological functions, while their impairment is responsible for endothelial dysfunction and cardiovascular disorders such as hypertension, atherosclerosis, and impaired wound healing and vascularization due to diabetes, infections, and ischemia. Upregulation of H2S producing enzymes and administration of H2S donors can be considered as innovative therapeutic approaches to improve EC biology and function, to revert endothelial dysfunction or to prevent cardiovascular disease progression. This review will focus on the beneficial autocrine/paracrine properties of H2S on ECs and the state of the art on H2S potentiating drugs and tools.

scholarly journals Bioinformatics analysis of the structural and evolutionary characteristics for toll-like receptor 15

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2079 ◽  
Author(s):  
Jinlan Wang ◽  
Zheng Zhang ◽  
Fen Chang ◽  
Deling Yin
Keyword(s):  
Convex Surface ◽  
Purifying Selection ◽  
Structural Features ◽  
Protein Docking ◽  
Activation Process ◽  
Docking Analysis ◽  
Unique Role ◽  
Evolutionarily Conserved ◽  
Interaction Interface ◽  
Tir Domains

Toll-like receptors (TLRs) play important role in the innate immune system. TLR15 is reported to have a unique role in defense against pathogens, but its structural and evolution characterizations are still poorly understood. In this study, we identified 57 completed TLR15 genes from avian and reptilian genomes. TLR15 clustered into an individual clade and was closely related to family 1 on the phylogenetic tree. Unlike the TLRs in family 1 with the broken asparagine ladders in the middle, TLR15 ectodomain had an intact asparagine ladder that is critical to maintain the overall shape of ectodomain. The conservation analysis found that TLR15 ectodomain had a highly evolutionarily conserved region on the convex surface of LRR11 module, which is probably involved in TLR15 activation process. Furthermore, the protein–protein docking analysis indicated that TLR15 TIR domains have the potential to form homodimers, the predicted interaction interface of TIR dimer was formed mainly by residues from the BB-loops andαC-helixes. Although TLR15 mainly underwent purifying selection, we detected 27 sites under positive selection for TLR15, 24 of which are located on its ectodomain. Our observations suggest the structural features of TLR15 which may be relevant to its function, but which requires further experimental validation.

scholarly journals Coupling Between Protein Level Selection and Codon Usage Optimization in the Evolution of Bacteria and Archaea

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Wenqi Ran ◽  
David M. Kristensen ◽  
Eugene V. Koonin
Keyword(s):  
Codon Usage ◽  
Protein Level ◽  
Codon Usage Bias ◽  
Protein Sequence ◽  
Gc Content ◽  
Protein Sequences ◽  
Microbial Evolution ◽  
Fine Tuning ◽  
Selection For ◽  
Genomic Gc Content

ABSTRACT The relationship between the selection affecting codon usage and selection on protein sequences of orthologous genes in diverse groups of bacteria and archaea was examined by using the Alignable Tight Genome Clusters database of prokaryote genomes. The codon usage bias is generally low, with 57.5% of the gene-specific optimal codon frequencies (F opt ) being below 0.55. This apparent weak selection on codon usage contrasts with the strong purifying selection on amino acid sequences, with 65.8% of the gene-specific dN/dS ratios being below 0.1. For most of the genomes compared, a limited but statistically significant negative correlation between F opt and dN/dS was observed, which is indicative of a link between selection on protein sequence and selection on codon usage. The strength of the coupling between the protein level selection and codon usage bias showed a strong positive correlation with the genomic GC content. Combined with previous observations on the selection for GC-rich codons in bacteria and archaea with GC-rich genomes, these findings suggest that selection for translational fine-tuning could be an important factor in microbial evolution that drives the evolution of genome GC content away from mutational equilibrium. This type of selection is particularly pronounced in slowly evolving, “high-status” genes. A significantly stronger link between the two aspects of selection is observed in free-living bacteria than in parasitic bacteria and in genes encoding metabolic enzymes and transporters than in informational genes. These differences might reflect the special importance of translational fine-tuning for the adaptability of gene expression to environmental changes. The results of this work establish the coupling between protein level selection and selection for translational optimization as a distinct and potentially important factor in microbial evolution. IMPORTANCE Selection affects the evolution of microbial genomes at many levels, including both the structure of proteins and the regulation of their production. Here we demonstrate the coupling between the selection on protein sequences and the optimization of codon usage in a broad range of bacteria and archaea. The strength of this coupling varies over a wide range and strongly and positively correlates with the genomic GC content. The cause(s) of the evolution of high GC content is a long-standing open question, given the universal mutational bias toward AT. We propose that optimization of codon usage could be one of the key factors that determine the evolution of GC-rich genomes. This work establishes the coupling between selection at the level of protein sequence and at the level of codon choice optimization as a distinct aspect of genome evolution.

scholarly journals Evolutionarily conserved cysteines in the stalk region of CD3‐epsilon are critical for T cell development and function

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Yibing Wang ◽  
Dean Becker ◽  
Tibor Vass ◽  
Janice White ◽  
Philippa Marrack ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Evolutionarily Conserved ◽  
And Function

scholarly journals Enhancing and inhibitory motifs have coevolved to regulate CD4 activity

2021 ◽  
Author(s):  
Mark S. Lee ◽  
Peter J. Tuohy ◽  
Caleb Kim ◽  
Katrina Lichauco ◽  
Heather L. Parrish ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Purifying Selection ◽  
Cell Receptor ◽  
Specific Information ◽  
Transmembrane Receptors ◽  
Peptide Antigens ◽  
And Function ◽  
Intracellular Domains

SUMMARYCD4+ T cells use T cell receptor (TCR)-CD3 complexes, and CD4, to respond to peptide antigens within MHCII molecules (pMHCII). We report here that, through ∼435 million years of evolution in jawed vertebrates, purifying selection has shaped motifs in the extracellular, transmembrane, and intracellular domains of eutherian CD4 that both enhance pMHCII responses and are coevolving with residues in an intracellular motif that inhibits pMHCII responses. Importantly, while CD4 interactions with the Src kinase, Lck, are classically viewed as the key determinant of CD4’s contribution to pMHCII responses, we found that without the inhibitory motif CD4-Lck interactions are not necessary for robust responses to pMHCII. In summary, motifs that mediate events on the outside and inside of CD4+ T cells coevolved to finetune the relay of pMHCII-specific information across the membrane. These results have implications for the evolution and function of complex transmembrane receptors and for biomimetic engineering.

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