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International Journal of Molecular... Feb 2024The , comprising 34 species, is a genus of Gentianaceae. Members of are mostly perennial, entwined herbs with high medicinal value and rich in iridoids, xanthones,...
The , comprising 34 species, is a genus of Gentianaceae. Members of are mostly perennial, entwined herbs with high medicinal value and rich in iridoids, xanthones, flavonoids, and triterpenes. However, our inadequate understanding of the differences in the plastid genome sequences of species has severely hindered the study of their evolution and phylogeny. Therefore, we first analyzed the 86 Gentianae plastid genomes to explore the phylogenetic relationships within the Gentianae subfamily where is located. Then, we analyzed six plastid genomes of , including two newly sequenced plastid genomes and four previously published plastid genomes, to explore the plastid genomes' evolution and phylogenetic relationships in the genus . The plastomes have a quadripartite structure and are between 150,929 and 151,350 bp in size. The plastomes of encoding 134 genes were detected, including 86 protein-coding genes (CDS), 37 transfer RNA (tRNA) genes, eight ribosomal RNA (rRNA) genes, and three pseudogenes (, , and ). The result of the comparison shows that the plastomes are very conserved, with the total plastome GC content ranging from 37.70% to 37.79%. In repeat sequence analysis, the number of single nucleotide repeats (A/T) varies among the six species, and the identified main long repeat types are forward and palindromic repeats. The degree of conservation is higher at the SC/IR boundary. The regions with the highest divergence in the CDS and the intergenic region (IGS) are and , respectively. The average pi of the CDS and the IGS are only 0.071% and 0.232%, respectively, indicating that the plastomes are highly conserved. Phylogenetic analysis indicated that Gentianinae is divided into two clades, with as a sister to . Phylogenetic trees based on CDS and CDS + IGS combined matrices have strong support in . These findings contribute to the elucidation of the plastid genome evolution of and provide a foundation for further exploration and resource utilization within this genus.
Topics: Phylogeny; Genome, Plastid; Gentianaceae; Evolution, Molecular
PubMed: 38473781
DOI: 10.3390/ijms25052534 -
Bioinformatics Advances 2024The recently published T2T-CHM13 reference assembly completed the annotation of the final 8% of the human genome. It introduced 1956 genes, close to 100 of which are...
SUMMARY
The recently published T2T-CHM13 reference assembly completed the annotation of the final 8% of the human genome. It introduced 1956 genes, close to 100 of which are predicted to be coding because they have a protein coding parent gene. Here, we confirm the coding status and functional relevance of two of these genes, paralogues of and . We find that , one of four novel subtelomeric WASH1 genes uncovered in the new assembly, produces the WASH1 protein that forms part of the vital actin-regulatory WASH complex. Its coding status is supported by abundant proteomics, conservation, and cDNA evidence. It was previously assumed that gene produced the functional WASH1 protein, but new evidence shows that is a human-derived duplication and likely to be one of 12 WASH1 pseudogenes in the human gene set. We also find that the T2T-CHM13 assembly has added a functionally important copy of to the human gene set. We demonstrate that uniquely mapping peptides from proteomics databases support the novel rather than the GRCh38 assembly gene. These new additions to the set of human coding genes underlines the importance of the new T2T-CHM13 assembly.
AVAILABILITY AND IMPLEMENTATION
None.
PubMed: 38464973
DOI: 10.1093/bioadv/vbae029 -
Stem Cells Translational Medicine May 2024Adipose stem cell (ASC)-based therapies provide an encouraging option for tissue repair and regeneration. However, the function of these cells declines with aging, which...
Adipose stem cell (ASC)-based therapies provide an encouraging option for tissue repair and regeneration. However, the function of these cells declines with aging, which limits their clinical transformation. Recent studies have outlined the involvement of long non-coding RNAs in stem cell aging. Here, we reanalyzed our published RNA sequencing (RNA-seq) data profiling differences between ASCs from young and old donors and identified a lncRNA named double homeobox A pseudogene 10 (DUXAP10) as significantly accumulated in aged ASCs. Knocking down DUXAP10 promoted stem cell proliferation and migration and halted cell senescence and the secretion of proinflammatory cytokines. In addition, DUXAP10 was located in the cytoplasm and functioned as a decoy for miR-214-3p. miR-214-3p was downregulated in aged ASCs, and its overexpression rejuvenated aged ASCs and reversed the harm caused by DUXAP10. Furthermore, Ras Association Domain Family Member 5 (RASSF5) was the target of miR-214-3p and was upregulated in aged ASCs. Overexpressing DUXAP10 and inhibiting miR-214-3p both enhanced RASSF5 content in ASCs, while DUXAP10 knockdown promoted the therapeutic ability of aged ASCs for skin wound healing. Overall, this study offers new insights into the mechanism of age-related ASC dysfunction and names DUXAP10 and miR-214-3p as potential targets for energizing aged stem cells.
Topics: MicroRNAs; Humans; RNA, Long Noncoding; Animals; Mice; Adipose Tissue; Stem Cells; Cellular Senescence; Rejuvenation; Cell Proliferation; Gene Knockdown Techniques
PubMed: 38459853
DOI: 10.1093/stcltm/szae015 -
Microbiology Spectrum Apr 2024Bacteria have evolved diverse defense mechanisms to counter bacteriophage attacks. Genetic programs activated upon infection characterize phage-host molecular...
UNLABELLED
Bacteria have evolved diverse defense mechanisms to counter bacteriophage attacks. Genetic programs activated upon infection characterize phage-host molecular interactions and ultimately determine the outcome of the infection. In this study, we applied ribosome profiling to monitor protein synthesis during the early stages of sk1 bacteriophage infection in . Our analysis revealed major changes in gene expression within 5 minutes of sk1 infection. Notably, we observed a specific and severe downregulation of several operons which encode enzymes required for uridine monophosphate biosynthesis. Consistent with previous findings, this is likely an attempt of the host to starve the phage of nucleotides it requires for propagation. We also observed a gene expression response that we expect to benefit the phage. This included the upregulation of 40 ribosome proteins that likely increased the host's translational capacity, concurrent with a downregulation of genes that promote translational fidelity ( and ). In addition to the characterization of host-phage gene expression responses, the obtained ribosome profiling data enabled us to identify two putative recoding events as well as dozens of loci currently annotated as pseudogenes that are actively translated. Furthermore, our study elucidated alterations in the dynamics of the translation process, as indicated by time-dependent changes in the metagene profile, suggesting global shifts in translation rates upon infection. Additionally, we observed consistent modifications in the ribosome profiles of individual genes, which were apparent as early as 2 minutes post-infection. The study emphasizes our ability to capture rapid alterations of gene expression during phage infection through ribosome profiling.
IMPORTANCE
The ribosome profiling technology has provided invaluable insights for understanding cellular translation and eukaryotic viral infections. However, its potential for investigating host-phage interactions remains largely untapped. Here, we applied ribosome profiling to cultures infected with sk1, a major infectious agent in dairy fermentation processes. This revealed a profound downregulation of genes involved in pyrimidine nucleotide synthesis at an early stage of phage infection, suggesting an anti-phage program aimed at restricting nucleotide availability and, consequently, phage propagation. This is consistent with recent findings and contributes to our growing appreciation for the role of nucleotide limitation as an anti-viral strategy. In addition to capturing rapid alterations in gene expression levels, we identified translation occurring outside annotated regions, as well as signatures of non-standard translation mechanisms. The gene profiles revealed specific changes in ribosomal densities upon infection, reflecting alterations in the dynamics of the translation process.
Topics: Protein Biosynthesis; Ribosome Profiling; Down-Regulation; Bacteriophages; RNA, Messenger; Nucleotides; Uridine Monophosphate; Lactococcus
PubMed: 38451091
DOI: 10.1128/spectrum.03989-23 -
BMC Research Notes Mar 2024Male infertility accounts for approximately 30% of cases of reproductive failure. The characterization of genetic variants using cytogenomic techniques is essential for...
OBJECTIVES
Male infertility accounts for approximately 30% of cases of reproductive failure. The characterization of genetic variants using cytogenomic techniques is essential for the adequate clinical management of these patients. We aimed to conduct a cytogenetic investigation of numerical and structural rearrangements and a genomic study of Y chromosome microdeletions/microduplications in infertile men derived from a single centre with over 14 years of experience.
RESULTS
We evaluated 151 infertile men in a transversal study using peripheral blood karyotypes and 15 patients with normal karyotypes through genomic investigation by multiplex ligation-dependent probe amplification (MLPA) or polymerase chain reaction of sequence-tagged sites (PCR-STS) techniques. Out of the 151 patients evaluated by karyotype, 13 presented chromosomal abnormalities: two had numerical alterations, and 11 had structural chromosomal rearrangements. PCR-STS detected a BPY2 gene region and RBMY2DP pseudogene region microdeletion in one patient. MLPA analysis allowed the identification of one patient with CDY2B_1 and CDY2B_2 probe duplications (CDY2B and NLGN4Y genes) and one patient with BPY2_1, BPY2_2, and BPY2_4 probe duplications (PRY and RBMY1J genes).
Topics: Humans; Male; Brazil; Genomics; Infertility, Male; Genetic Services; Karyotyping; Multiplex Polymerase Chain Reaction
PubMed: 38444014
DOI: 10.1186/s13104-024-06710-1 -
PLoS Genetics Mar 2024The honey bee trypanosomatid parasite, Lotmaria passim, contains two genes that encode the flagellar calcium binding protein (FCaBP) through tandem duplication in its...
The honey bee trypanosomatid parasite, Lotmaria passim, contains two genes that encode the flagellar calcium binding protein (FCaBP) through tandem duplication in its genome. FCaBPs localize in the flagellum and entire body membrane of L. passim through specific N-terminal sorting sequences. This finding suggests that this is an example of protein subcellular relocalization resulting from gene duplication, altering the intracellular localization of FCaBP. However, this phenomenon may not have occurred in Leishmania, as one or both of the duplicated genes have become pseudogenes. Multiple copies of the FCaBP gene are present in several Trypanosoma species and Leptomonas pyrrhocoris, indicating rapid evolution of this gene in trypanosomatid parasites. The N-terminal flagellar sorting sequence of L. passim FCaBP1 is in close proximity to the BBSome complex, while that of Trypanosoma brucei FCaBP does not direct GFP to the flagellum in L. passim. Deletion of the two FCaBP genes in L. passim affected growth and impaired flagellar morphogenesis and motility, but it did not impact host infection. Therefore, FCaBP represents a duplicated gene with a rapid evolutionary history that is essential for flagellar structure and function in a trypanosomatid parasite.
Topics: Bees; Animals; Calcium-Binding Proteins; Parasites; Leishmania; Flagella; Cilia
PubMed: 38437202
DOI: 10.1371/journal.pgen.1011195 -
Bioinformatics (Oxford, England) Mar 2024Large-scale gene expression studies allow gene network construction to uncover associations among genes. To study direct associations among genes, partial...
MOTIVATION
Large-scale gene expression studies allow gene network construction to uncover associations among genes. To study direct associations among genes, partial correlation-based networks are preferred over marginal correlations. However, FDR control for partial correlation-based network construction is not well-studied. In addition, currently available partial correlation-based methods cannot take existing biological knowledge to help network construction while controlling FDR.
RESULTS
In this paper, we propose a method called Partial Correlation Graph with Information Incorporation (PCGII). PCGII estimates partial correlations between each pair of genes by regularized node-wise regression that can incorporate prior knowledge while controlling the effects of all other genes. It handles high-dimensional data where the number of genes can be much larger than the sample size and controls FDR at the same time. We compare PCGII with several existing approaches through extensive simulation studies and demonstrate that PCGII has better FDR control and higher power. We apply PCGII to a plant gene expression dataset where it recovers confirmed regulatory relationships and a hub node, as well as several direct associations that shed light on potential functional relationships in the system. We also introduce a method to supplement observed data with a pseudogene to apply PCGII when no prior information is available, which also allows checking FDR control and power for real data analysis.
AVAILABILITY AND IMPLEMENTATION
R package is freely available for download at https://cran.r-project.org/package=PCGII.
Topics: Gene Regulatory Networks; Algorithms; Computer Simulation; Genes, Plant; Sample Size
PubMed: 38430463
DOI: 10.1093/bioinformatics/btae125 -
Nucleic Acids Research May 2024microRNAs (miRNAs) regulate nearly all physiological processes but our understanding of exactly how they function remains incomplete, particularly in the context of...
microRNAs (miRNAs) regulate nearly all physiological processes but our understanding of exactly how they function remains incomplete, particularly in the context of viral infections. Here, we adapt a biochemical method (CLEAR-CLIP) and analysis pipeline to identify targets of miRNAs in lung cells infected with Respiratory syncytial virus (RSV). We show that RSV binds directly to miR-26 and miR-27 through seed pairing and demonstrate that these miRNAs target distinct gene networks associated with cell cycle and metabolism (miR-27) and antiviral immunity (miR-26). Many of the targets are de-repressed upon infection and we show that the miR-27 targets most sensitive to miRNA inhibition are those associated with cell cycle. Finally, we demonstrate that high confidence chimeras map to long noncoding RNAs (lncRNAs) and pseudogenes in transcriptional regulatory regions. We validate that a proportion of miR-27 and Argonaute 2 (AGO2) is nuclear and identify a long non-coding RNA (lncRNA) as a miR-27 target that is linked to transcriptional regulation of nearby genes. This work expands the target networks of miR-26 and miR-27 to include direct interactions with RSV and lncRNAs and implicate these miRNAs in regulation of key genes that impact the viral life cycle associated with cell cycle, metabolism, and antiviral immunity.
Topics: Humans; Argonaute Proteins; Cell Cycle; Cell Line; Gene Expression Regulation; Gene Regulatory Networks; Host-Pathogen Interactions; MicroRNAs; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Syncytial Viruses; RNA, Long Noncoding
PubMed: 38412296
DOI: 10.1093/nar/gkae116 -
Frontiers in Veterinary Science 2024Studies carried out in several species have demonstrated that detection of low-calorie sweeteners in the lumen of the intestine, by the sweet receptor, T1R2-T1R3,...
Studies carried out in several species have demonstrated that detection of low-calorie sweeteners in the lumen of the intestine, by the sweet receptor, T1R2-T1R3, initiates a signaling pathway leading to enhanced expression and activity of intestinal Na/glucose cotransporter 1, SGLT1. This results in an increased gut capacity to absorb glucose, sodium chloride and water, the basis for oral rehydration therapy. Horses express T1R2, T1R3 and downstream signaling elements in the intestinal tissue. As such, the potential of sweetener-stimulation of T1R2-T1R3 leading to upregulation of SGLT1 allows the provision of more glucose (energy) and hydration for horses. This is especially important when the need for glucose increases during strenuous exercise, pregnancy, and lactation. There are significant differences among species in the ability to detect sweeteners. Amino acid substitutions and pseudogenization of taste receptor genes underlie these variations. Nothing is known about the sweetener specificity of horse T1R2-T1R3. Using heterologous expression methodology, we demonstrate that sweeteners sucralose, stevia and neohesperidin dihydrochalcone (NHDC) activate horse T1R2-T1R3, but cyclamate does not. Determination of sweetener specificity of equine sweet receptor is crucial for developing suitable dietary additives to optimize glucose absorption, hydration and avoiding the intestinal disease brought about by microbial fermentation of unabsorbed carbohydrate reaching the large intestine.
PubMed: 38410741
DOI: 10.3389/fvets.2024.1325135 -
Cureus Jan 2024Background In addition to genetic predisposition, occupational and environmental factors are important for the risk of prostate cancer. We investigated the effect of...
Background In addition to genetic predisposition, occupational and environmental factors are important for the risk of prostate cancer. We investigated the effect of single nucleotide polymorphisms (SNPs) on the development of prostate cancer in Japan, including occupational and industrial history as confounding factors in addition to age, smoking, and alcohol drinking. Methods We enrolled 210 prostate cancer patients and 504 male control patients. We conducted four genome-wide association study (GWAS) patterns for prostate cancer development. In the association test, logistic regression models incorporated age, smoking history, alcohol consumption history, and each pattern of industrial/occupational classification. Results No SNPs satisfying the genome-wide significance level of 5×10 were detected in GWAS. SNPs with a suggestive association level of 1×10 were found near the long intergenic non-protein coding RNA 1824 () and tripartite motif family like 2 () genes in the GWAS using occupational history as a confounder and near the ribosomal protein S2 pseudogene 25 () gene in the GWAS using industrial history as a confounder. No SNPs that met the suggestive association level were observed in the GWAS that did not include occupational and industrial history. Conclusion By adding occupational and industrial history to the confounding factors, there were SNPs detected in the GWAS for prostate cancer development. The consideration of occupational and industrial history may increase the usefulness of GWAS.
PubMed: 38406143
DOI: 10.7759/cureus.52926