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Genome Biology and Evolution Jun 2024De novo genes emerge from non-coding regions of genomes via succession of mutations. Among others, such mutations activate transcription and create a new open reading...
De novo genes emerge from non-coding regions of genomes via succession of mutations. Among others, such mutations activate transcription and create a new open reading frame (ORF). Although the mechanisms underlying ORF emergence are well documented, relatively little is known about the mechanisms enabling new transcription events. Yet, in many species a continuum between absent and very prominent transcription has been reported for essentially all regions of the genome. In this study we searched for de novo transcripts by using newly assembled genomes and transcriptomes of seven inbred lines of Drosophila melanogaster, originating from six European and one African population. This setup allowed us to detect sample specific de novo transcripts, and compare them to their homologous non-transcribed regions in other samples, as well as genic and intergenic control sequences. We studied the association with transposable elements and the enrichment of transcription factor motifs upstream of de novo emerged transcripts and compared them with regulatory elements. We found that de novo transcripts overlap with TEs more often than expected by chance. The emergence of new transcripts correlates with regions of high GC content and TE expression. Moreover, upstream regions of de novo transcripts are highly enriched with regulatory motifs. Such motifs are more enriched in new transcripts overlapping with TEs, particularly DNA TEs, and are more conserved upstream de novo transcripts than upstream their 'non-transcribed homologs'. Overall, our study demonstrates that TE insertion is important for transcript emergence, partly by introducing new regulatory motifs from DNA TE families.
PubMed: 38934893
DOI: 10.1093/gbe/evae134 -
Genome Biology and Evolution Jun 2024During evolution, new ORFs with the potential to give rise to novel proteins continuously emerge. A recent compilation of non-canonical ORFs with translation signatures...
During evolution, new ORFs with the potential to give rise to novel proteins continuously emerge. A recent compilation of non-canonical ORFs with translation signatures in humans has identified thousands of cases with a putative de novo origin. However, it is not known which is their distribution in the population. Are they universally translated? Here we use ribosome profiling data from 65 lymphoblastoid cell lines from individuals of Yoruba origin to investigate this question. We identify 2,587 de novo ORFs translated in at least one of the cell lines. In line with their de novo origin, the encoded proteins tend to be smaller than 100 amino acids and encode positively charged proteins. We observe that the de novo ORFs are more polymorphic in the population than the set of canonical proteins, with a substantial fraction of them being translated in only some of the cell lines. Remarkably, this difference remains significant after controlling for differences in the translation levels. These results suggest that variations in the level translation of de novo ORFs could be a relevant source of intra-species phenotypic diversity in humans.
PubMed: 38934859
DOI: 10.1093/gbe/evae126 -
Frontiers in Genome Editing 2024Rice, a staple food for a significant portion of the global population, faces persistent threats from various pathogens and pests, necessitating the development of... (Review)
Review
Rice, a staple food for a significant portion of the global population, faces persistent threats from various pathogens and pests, necessitating the development of resilient crop varieties. Deployment of resistance genes in rice is the best practice to manage diseases and reduce environmental damage by reducing the application of agro-chemicals. Genome editing technologies, such as CRISPR-Cas, have revolutionized the field of molecular biology, offering precise and efficient tools for targeted modifications within the rice genome. This study delves into the application of these tools to engineer novel alleles of resistance genes in rice, aiming to enhance the plant's innate ability to combat evolving threats. By harnessing the power of genome editing, researchers can introduce tailored genetic modifications that bolster the plant's defense mechanisms without compromising its essential characteristics. In this study, we synthesize recent advancements in genome editing methodologies applicable to rice and discuss the ethical considerations and regulatory frameworks surrounding the creation of genetically modified crops. Additionally, it explores potential challenges and future prospects for deploying edited rice varieties in agricultural landscapes. In summary, this study highlights the promise of genome editing in reshaping the genetic landscape of rice to confront emerging challenges, contributing to global food security and sustainable agriculture practices.
PubMed: 38933684
DOI: 10.3389/fgeed.2024.1415244 -
Frontiers in Cell and Developmental... 2024Endometriosis (EM), characterized by ectopic growth of endometrial tissues and recurrent pelvic pain, is a common disease with severe negative impacts on the life... (Review)
Review
Endometriosis (EM), characterized by ectopic growth of endometrial tissues and recurrent pelvic pain, is a common disease with severe negative impacts on the life quality of patients. Conventional uterine tissue transplantation-based models have been broadly used to investigate the pathogenic mechanism(s) of EM. Transgenic mice with whole body or uterine/pelvic tissue-specific labelling by the expression of GFP, β-gal or other light-emitting or chromogenic markers enable investigators to analyze the contribution to endometriotic lesions by the donor or recipient side after uterine tissue transplantation. Moreover, when coupled to uterine tissue transplantation, transgenic mice with a specific EM-related gene knocked out or overexpressed make it possible to determine the gene's role(s) for EM pathogenesis. Furthermore, observations on the rise of endometriotic lesions as well as structural/functional changes in the eutopic endometrium or pelvic tissues after gene manipulation will directly relate the cognate gene to the onset of EM. A major advantage of transgenic EM models is their efficiency for analyzing gene interactions with hormonal, dietetic and/or environmental factors. This review summarizes the features/sources/backgrounds of transgenic mice and their applications to EM studies concerning hormonal regulation, angiogenesis and inflammation. Findings from these studies, the advantages/disadvantages of transgenic EM models, and future expectations are also discussed.
PubMed: 38933332
DOI: 10.3389/fcell.2024.1376414 -
Vaccines Jun 2024As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged,... (Review)
Review
As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged, including new-onset antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV). We systematically reviewed new-onset AAV following COVID-19 vaccination case reports and case series published in three databases before January 2024 following PRISMA guidelines to understand the characteristics of possible causal relationships or coincidences. In total, 404 articles were screened respectively by title, abstracts, and full-texts. Thirty-four papers fulfilled the inclusion criteria and have been analyzed, covering 44 patients with new-onset AAV after COVID-19 vaccination with no prior history of COVID-19 infection. Data regarding patients' metrics, comorbidities, vaccination characteristics, symptoms, diagnostics, treatment, and outcomes were investigated and summarized. The cohort consisted predominantly of females. AAV diagnosis was confirmed via biopsy, with renal dysfunction as a prevailing manifestation. In most cases, the first symptoms of AAV developed after the second dose; moreover, Pfizer-BioNTech was the most frequently administered vaccine among the analyzed cohort. Primary treatment involved glucocorticoid therapy, with a mostly favourable response. This systematic review aims to raise awareness among clinicians in the field regarding this rare but possible complication, to promote the prompt recognition and diagnosis of de novo ANCA-positive small-vessel vasculitis in timely association with SARS-CoV-2 vaccination.
PubMed: 38932385
DOI: 10.3390/vaccines12060656 -
Viruses May 2024The alewife ( is an anadromous herring that inhabits waters of northeastern North America. This prey species is a critical forage for piscivorous birds, mammals, and...
The alewife ( is an anadromous herring that inhabits waters of northeastern North America. This prey species is a critical forage for piscivorous birds, mammals, and fishes in estuarine and oceanic ecosystems. During a discovery project tailored to identify potentially emerging pathogens of this species, we obtained the full genome of a novel hepadnavirus (ApHBV) from clinically normal alewives collected from the Maurice River, Great Egg Harbor River, and Delaware River in New Jersey, USA during 2015-2018. This previously undescribed hepadnavirus contained a circular DNA genome of 3146 nucleotides. Phylogenetic analysis of the polymerase protein placed this virus in the clade of metahepadnaviruses (family: ; genus: ). There was no evidence of pathology in the internal organs of infected fish and virions were not observed in liver tissues by electron microscopy. We developed a Taqman-based quantitative (qPCR) assay and screened 182 individuals collected between 2015 and 2018 and detected additional qPCR positives (n = 6). An additional complete genome was obtained in 2018 and it has 99.4% genome nucleotide identity to the first virus. Single-nucleotide polymorphisms were observed between the two genomes, including 7/9 and 12/8 synonymous vs nonsynonymous mutations across the polymerase and surface proteins, respectively. While there was no evidence that this virus was associated with disease in this species, alewives are migratory interjurisdictional fishes of management concern. Identification of microbial agents using de novo sequencing and other advanced technologies is a critical aspect of understanding disease ecology for informed population management.
Topics: Animals; Genome, Viral; Phylogeny; Fish Diseases; Hepadnaviridae; Fishes; Genomics; Hepadnaviridae Infections; New Jersey
PubMed: 38932117
DOI: 10.3390/v16060824 -
Nutrients Jun 2024High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and...
BACKGROUND
High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and fish oil are considered to be a part of healthy diets. However, their differential effects on gut microbiome perturbations in mice fed high concentrations of these fats, in the absence of sucrose, remains to be elucidated. The aim of the study was to test whether the sucrose-free cocoa butter-based high-fat diet (C-HFD) feeding in mice leads to gut dysbiosis that associates with a pathologic phenotype marked by hepatic steatosis, low-grade inflammation, perturbed glucose homeostasis, and insulin resistance, compared with control mice fed the fish oil based high-fat diet (F-HFD).
RESULTS
C57BL/6 mice (5-6 mice/group) were fed two types of high fat diets (C-HFD and F-HFD) for 24 weeks. No significant difference was found in the liver weight or total body weight between the two groups. The 16S rRNA sequencing of gut bacterial samples displayed gut dysbiosis in C-HFD group, with differentially-altered microbial diversity or relative abundances. , and were highly abundant in C-HFD group, while the , (TM7), , and were more abundant in F-HFD group. Other taxa in C-HFD group included the (AF12), and An increased Firmicutes/Bacteroidetes (F/B) ratio in C-HFD group, compared with F-HFD group, indicated the gut dysbiosis. These gut bacterial changes in C-HFD group had predicted associations with fatty liver disease and with lipogenic, inflammatory, glucose metabolic, and insulin signaling pathways. Consistent with its microbiome shift, the C-HFD group showed hepatic inflammation and steatosis, high fasting blood glucose, insulin resistance, increased hepatic de novo lipogenesis (Acetyl CoA carboxylases 1 (), Fatty acid synthase (), Stearoyl-CoA desaturase-1 (), Elongation of long-chain fatty acids family member 6 (), Peroxisome proliferator-activated receptor-gamma () and cholesterol synthesis (β-(hydroxy β-methylglutaryl-CoA reductase (). Non-significant differences were observed regarding fatty acid uptake (Cluster of differentiation 36 (), Fatty acid binding protein-1 () and efflux (ATP-binding cassette G1 (), Microsomal TG transfer protein () in C-HFD group, compared with F-HFD group. The C-HFD group also displayed increased gene expression of inflammatory markers including Tumor necrosis factor alpha (), C-C motif chemokine ligand 2 (), and Interleukin-12 (), as well as a tendency for liver fibrosis.
CONCLUSION
These findings suggest that the sucrose-free C-HFD feeding in mice induces gut dysbiosis which associates with liver inflammation, steatosis, glucose intolerance and insulin resistance.
Topics: Animals; Dysbiosis; Gastrointestinal Microbiome; Insulin Resistance; Diet, High-Fat; Mice, Inbred C57BL; Male; Mice; Fatty Liver; Liver; Dietary Fats; Sucrose
PubMed: 38931284
DOI: 10.3390/nu16121929 -
Plants (Basel, Switzerland) Jun 2024Interaction between transcription factors (TFs) and motifs is essential for gene regulation and the subsequent phenotype formation. Soybean () JAGGEED 1 (GmJAG1) is a...
Interaction between transcription factors (TFs) and motifs is essential for gene regulation and the subsequent phenotype formation. Soybean () JAGGEED 1 (GmJAG1) is a key TF that controls leaf shape, seed number and flower size. To understand the GmJAG1 binding motifs, in this study, we performed the GmJAG1 DNA affinity purification sequencing (DAP-seq) experiment, which is a powerful tool for the de novo motif prediction method. Two new significant GmJAG1 binding motifs were predicted and the EMSA experiments further verified the ability of GmJAG1 bound to these motifs. The potential binding sites in the downstream gene promoter were identified through motif scanning and a potential regulatory network mediated by GmJAG1 was constructed. These results served as important genomic resources for further understanding the regulatory mechanism of GmJAG1.
PubMed: 38931140
DOI: 10.3390/plants13121708 -
Molecules (Basel, Switzerland) Jun 2024The discovery and investigation of new natural compounds with antimicrobial activity are new potential strategies to reduce the spread of antimicrobial resistance. The...
The discovery and investigation of new natural compounds with antimicrobial activity are new potential strategies to reduce the spread of antimicrobial resistance. The presented study reveals, for the first time, the promising antibacterial potential of two fractions from mucus with an MW < 20 kDa and an MW > 20 kDa against five bacterial pathogens- 1085, 1897, 8691, 3915, and 8754. Using de novo sequencing, 16 novel peptides with potential antibacterial activity were identified in a fraction with an MW < 20 kDa. Some bioactive compounds in a mucus fraction with an MW > 20 kDa were determined via a proteomic analysis on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and bioinformatics. High homology with proteins and glycoproteins was found, with potential antibacterial activity in mucus proteins named aspernin, hemocyanins, H-lectins, and L-amino acid oxidase-like protein, as well as mucins (mucin-5AC, mucin-5B, mucin-2, and mucin-17). We hypothesize that the synergy between the bioactive components determined in the composition of the fraction > 20 kDa are responsible for the high antibacterial activity against the tested pathogens in concentrations between 32 and 128 µg/mL, which is comparable to vancomycin, but without cytotoxic effects on model eukaryotic cells of . Additionally, a positive effect, by reducing the levels of intracellular oxidative damage and increasing antioxidant capacity, on cells was found for both mucus extract fractions of . These findings may serve as a basis for further studies to develop a new antibacterial agent preventing the development of antibiotic resistance.
Topics: Anti-Bacterial Agents; Mucus; Microbial Sensitivity Tests; Peptides; Enterococcus faecalis; Enterococcus faecium; Bacillus cereus; Animals; Propionibacterium acnes; Salmonella enterica
PubMed: 38930951
DOI: 10.3390/molecules29122886 -
Journal of Clinical Medicine Jun 2024Estrogen receptor (ER)-positive breast cancer (BC) is the most common BC subtype. Endocrine therapy (ET) targeting ER signaling still remains the mainstay treatment... (Review)
Review
Estrogen receptor (ER)-positive breast cancer (BC) is the most common BC subtype. Endocrine therapy (ET) targeting ER signaling still remains the mainstay treatment option for hormone receptor (HR)-positive BC either in the early or in advanced setting, including different strategies, such as the suppression of estrogen production or directly blocking the ER pathway through SERMs-selective estrogen receptor modulators-or SERDs-selective estrogen receptor degraders. Nevertheless, the development of de novo or acquired endocrine resistance still remains challenging for oncologists. The use of novel ET combined with targeted drugs, such as cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, has significantly improved long-term outcome rates, thus changing the therapeutic algorithm for metastatic BC (MBC) and recently the therapeutic strategy in the adjuvant setting for early high-risk BC. Eluding the resistance to CDK4/6 inhibitors combined with ET is currently an unmet medical need, and there is disagreement concerning the best course of action for patients who continue to progress after this combination approach. Genetic changes in the tumor along its growth uncovered by genomic profiling of recurrent and/or metastatic lesions through tumor and/or liquid biopsies may predict the response or resistance to specific agents, suggesting the best therapeutic strategy for each patient by targeting the altered ER-dependent pathway (novel oral SERDs and a new generation of anti-estrogen agents) or alternative ER-independent signaling pathways such as PI3K/AKT/mTOR or tyrosine kinase receptors ( mutations or HER2 low status) or by inhibiting pathways weakened through germline mutations. These agents are being investigated as single molecules and in combination with other target therapies, offering promising weapons to overcome or avoid treatment failure and propose increasingly more personalized treatment approaches. This review presents novel insights into ET and other targeted therapies for managing metastatic HR/HER2 BC by exploring potential strategies based on clinical evidence and genomic profiling following the failure of the CDK4/6i and ET combination.
PubMed: 38930141
DOI: 10.3390/jcm13123611