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At least 163 records · Page 9Linked to original sources
PubMed2026

Dental wastewater reveals a hidden reservoir of oral bacteriophage diversity.

Bacteriophages (phages) are being explored as alternatives or complements to antibiotics because of their ability to selectively kill bacterial pathogens. However, phages that infect many oral bacteria remain undiscovered. Here, we discovered that dental wastewater harbors previously underexplored phage diversity. Viral particles concentrated from dental wastewater displayed diverse morphologies, including abundant filamentous phage-like particles. Deep long-read metagenomic sequencing of concentrated viral particles generated 7.4 billion bases of sequence data and yielded 255 medium- to high-quality viral operational taxonomic units (vOTUs), including 46 predicted complete genomes. Comparison with large phage databases revealed that 63 of these 255 vOTUs had no detectable match, indicating that extensive sequencing of dental wastewater substantially expands the number of potential bacteriophages associated with the human oral microbiome. Host prediction linked many vOTUs to oral-associated bacterial taxa, including species with few or no previously reported phages, such as Porphyromonas gingivalis, Tannerella forsythia, and Candidatus Saccharibacteria. Functional annotation identified diverse genes associated with antiphage defense systems within a subset of vOTUs, suggesting that oral phages may contribute to the movement of genes encoding bacterial immune functions within the oral microbiome. Together, these findings expand the known oral phageome and show that dental wastewater contains a largely untapped diversity of phages.IMPORTANCEThe human oral cavity contains a diverse microbial community, but the bacteriophages (phages) that infect many oral bacteria remain poorly characterized. This gap limits our understanding of how phages shape oral microbial communities. Here, we show that dental wastewater is an underexplored source of oral phage diversity. Deep long-read metagenomic sequencing revealed 255 medium- to high-quality phage operational taxonomic units, many of which are not present in existing oral phage databases. These genomes include predicted phages of periodontal disease-associated bacteria and other oral taxa with few or no known phages. Dental wastewater therefore expands the known human oral phageome and reveals candidate phages linked to bacteria associated with oral health and disease.

Bacteriophages↗
PubMed2025

Single-Cell Splicing Isoform Atlas of the Adult Human Heart and Heart Failure.

BACKGROUND: Alternative splicing plays crucial roles in normal heart development and cardiac disease by influencing protein-coding sequences, functional domains, and molecular networks. However, a detailed characterization of the human heart isoform landscape remains incomplete. METHODS: Leveraging long-read single-nucleus RNA sequencing and computational analysis, we dissected full-length isoform heterogeneities, expression patterns, and usage shifts across cell types, cell states, and cardiac conditions of the adult left ventricle. We applied in silico approaches to assess the functional relevance of identified isoforms; validated isoform compositions of representative cardiac genes using reverse transcription quantitative polymerase chain reaction and targeted amplicon sequencing; and developed a web server for interactive navigation of our results. RESULTS: The data revealed that isoform heterogeneity is widespread in the cardiac cellular system, serving as a posttranscriptional buffer mechanism that calibrates the molecule reservoirs in human hearts. In healthy left ventricles, ≈30% of cell type-specific genes were polyform, using multiple isoforms tailored to cell type-specific programs. Among ubiquitously expressed genes, >300 showed differential isoform usage with cell type specificity in normal hearts. Comparisons of cardiomyocytes across conditions uncovered 379 genes with marked isoform usage shifts, most of which are predicted to change protein coding outcomes through direct changes in protein coding sequences and switches between intron retention and non-protein-coding biotypes. In contrast, cell state-specific programs tend to operate on monoform genes associated with changes among cell states. In addition, our data revealed heart failure-associated differential isoform usage events in stromal and immune cell types in the cardiac microenvironment. CONCLUSIONS: We present a comprehensive atlas of splicing isoforms in the normal adult heart and heart failure through long-read single-nucleus RNA sequencing and computational analyses. The results suggest crucial roles of isoforms in buffering core cellular programs and contributing to disease-associated cell states. The full-length details of these cell-specific isoforms serve as an important reference for downstream translational and mechanistic studies and are available on our online data portal at https://github.com/gaolabtools/heart-isoform-atlas.

Humans↗
PubMed1999

A long open reading frame in the mitochondrial LSU rRNA group-I intron of Cryphonectria parasitica encodes a putative S5 ribosomal protein fused to a maturase.

A 4238-bp intervening sequence within the highly conserved U11 region of the mitochondrial large subunit ribosomal RNA gene of the fungus Cryphonectria parasitica Ep155 has been sequenced and identified to be a group-I intron. This is the largest group-I intron reported to-date for fungal mitochondrial genomes. The intron contains an 851-codon open reading frame encoding a putative, but complete, small-subunit ribosomal protein of 510 amino acids which is fused at its carboxyl terminus to a 311 amino-acid polypeptide representing a typical maturase-like protein. A short open reading frame of 83 amino acids with some similarity to maturases, but lacking a translation-initiation codon, was also noted at the 3' end of the intron. The unusual size of the intron and the arrangement of the open and truncated reading frames suggest that this segment of the mtDNA of C. parasitica has arisen by a fusion of components from two or more different introns, possibly involving the re-location of intronic genes.

Amino Acid Sequence↗
PubMed2006

Prokaryotes that grow optimally in acid have purine-poor codons in long open reading frames.

In nucleic acids the N-glycosyl bonds between purines and their ribose sugar moities are broken under acid conditions. If one strand of a duplex DNA segment were more vulnerable to mutation than the other, then the archaeon Picrophilus torridus, with an optimum growth pH near zero, could have adapted by decreasing the purine content of that strand. Yet, P. torridus has an optimum growth temperature near 60 degrees C, and thermophiles prefer purine-rich codons. We found that, as in other thermophiles, high growth temperature correlates with the use of purine-rich codons. The extra purines are often in third, non-amino acid determining, codon positions. However, as in other acidophiles, as open reading frame lengths increase, there is increased use of purine-poor codons, particularly those without purines in second, amino acid-determining, codon positions. Thus, P. torridus can be seen as adapting (a) to temperature by increasing its purines in all open reading frames without greatly impacting protein amino acid compositions, and (b) to pH by decreasing purines in longer open reading frames, thereby potentially impacting protein amino acid compositions. It is proposed that longer open reading frames, being larger mutational targets, have become less vulnerable to depurination by virtue of pyrimidine for purine substitutions.

Adaptation, Physiological↗
PubMed1987

Expression of a cDNA clone corresponding to the long open reading frame (XBL-I) of the bovine leukemia virus.

Nucleotide sequence analysis of a cDNA clone corresponding to the XBL-I open reading-frame of bovine leukemia virus (BLV) revealed that the AUG initiation codon was located 44 bases downstream from that of the env gene and was part of the p34x mRNA splice donor. . .ATGG/GTAA at the end of the pol gene sequence. RNA from this clone was synthesized in vitro by the SP6 RNA polymerase and translated into a 34,000 mol wt protein in rabbit reticulocyte lysates. The protein (p34x) is recognized in Western blots by most sera of BLV-infected sheep and tumor-bearing cattle, by an anti-synthetic peptide rabbit serum, and by the serum of a rabbit immunized by XBL-I RNA programmed reticulocyte lysates. Both sera react with a 34,000 mol wt protein present in nuclei of BLV-infected cells.

Base Sequence↗
PubMed1984

Generation of long read-through transcripts in vivo and in vitro by deletion of 3' termination and processing sequences in the human tRNAimet gene.

The effects of 3' deletions of the coding and flanking regions of the human tRNAimet gene on its transcription and subsequent processing have been studied both in vitro and in vivo. We demonstrate that in the absence of the oligo T stop signal, polymerase III will read-through efficiently to the next available downstream stop signal. In mutations preserving the 3' terminal sequence of the coding region these read-through transcripts are efficiently processed, irrespective of their length and sequence by an endonucleolytic cleavage to yield both a mature tRNA and an intact trailer RNA. However, deletions involving the terminal regions up to +62 in the coding sequence produce an unprocessed co-transcript of tRNA and downstream sequences. Deletions further within the B promoter box abolish transcription. The use of these mutants as possible "portable" promoters is discussed.

Animals↗
PubMed1992

Hepatitis B virus polymerase gene: expression of the long open reading frame using the baculovirus expression system.

A recombinant baculovirus was constructed containing a copy of the hepatitis B virus (HBV) genome which was inserted to produce an in-frame fusion of the precore (pre-C) coding region with the first 11 amino acids of the polyhedrin gene. The recombinant baculovirus expressed the 25K pre-C protein and two novel proteins, of approximately 93K and 72K. Both the 93K and 72K proteins are recognized by an anti-polymerase monoclonal antibody. Northern blot analysis of the mRNA produced during infection of Spodoptera frugiperda cells by the HBV recombinant baculovirus detected only one HBV mRNA species, suggesting that the three HBV-specific proteins expressed are translated from the same mRNA. No larger fusion proteins cross-reacting with either anti-core or polymerase antibodies were detected. These findings suggest that the two proteins encoded within the HBV polymerase gene are not produced via a core-polymerase fusion intermediate but by internal binding of ribosomes. These results are the first clear demonstration of efficient expression of two bona fide unprocessed polymerase proteins in a 1:1 ratio from an unspliced pre-C mRNA-like transcript. With the successful expression of the polymerase gene in insect cells it is now possible to produce large amounts of these proteins, allowing a more detailed structural and functional analysis of these proteins.

Baculoviridae↗
PubMed1991

The 120 kilodalton outer membrane protein (rOmp B) of Rickettsia rickettsii is encoded by an unusually long open reading frame: evidence for protein processing from a large precursor.

A Rickettsia rickettsii outer surface membrane protein (rOmp B), of an apparent molecular mass of 120 kilodaltons, is a major surface antigen of the Rickettsiae that displays genus, species, and sub-species specific antigenic determinants. The 5' portion of this gene was found to be unstable in plasmids, but was stably cloned in a lambda vector. The nucleotide sequence of the 5' terminus has been determined, thus completing the DNA sequence of the entire gene. Genetic analysis revealed an unusually large open reading frame with the capacity to encode a product much larger than the mature protein. A 32 kilodalton peptide from purified rickettsiae was isolated and the amino terminus was sequenced, which revealed that the peptide is encoded by the 3' portion of this large open reading frame. This suggests a role for post-translational processing of rOmp B from a large precursor molecule.

Amino Acid Sequence↗
PubMed2005

Characterization of the Tupaia rhabdovirus genome reveals a long open reading frame overlapping with P and a novel gene encoding a small hydrophobic protein.

Rhabdoviruses are negative-stranded RNA viruses of the order Mononegavirales and have been isolated from vertebrates, insects, and plants. Members of the genus Lyssavirus cause the invariably fatal disease rabies, and a member of the genus Vesiculovirus, Chandipura virus, has recently been associated with acute encephalitis in children. We present here the complete genome sequence and transcription map of a rhabdovirus isolated from cultivated cells of hepatocellular carcinoma tissue from a moribund tree shrew. The negative-strand genome of tupaia rhabdovirus is composed of 11,440 nucleotides and encodes six genes that are separated by one or two intergenic nucleotides. In addition to the typical rhabdovirus genes in the order N-P-M-G-L, a gene encoding a small hydrophobic putative type I transmembrane protein of approximately 11 kDa was identified between the M and G genes, and the corresponding transcript was detected in infected cells. Similar to some Vesiculoviruses and many Paramyxovirinae, the P gene has a second overlapping reading frame that can be accessed by ribosomal choice and encodes a protein of 26 kDa, predicted to be the largest C protein of these virus families. Phylogenetic analyses of the tupaia rhabdovirus N and L genes show that the virus is distantly related to the Vesiculoviruses, Ephemeroviruses, and the recently characterized Flanders virus and Oita virus and further extends the sequence territory occupied by animal rhabdoviruses.

Amino Acid Sequence↗
PubMed2026

Characterization and comparative analysis of the complete mitochondrial genome sequence of Aucklandia lappa Decne.

BACKGROUND: Aucklandia lappa Decne, a precious medicinal herb in China, utilises the dried rhizome as its medicinal part, which riches in volatile oils, sesquiterpene compounds and other active constituents. Although the mitogenome of A. lappa has been assembled, related research remains in its preliminary stages, far from achieving comprehensive and in-depth understanding. RESULTS: In this paper, the complete mitogenome of A. lappa was assembled by employing a hybrid strategy that combined Illumina short-read and Nanopore long-read sequencing. The assembled mitogenome is 436,648 bp in size with a GC content of 45.06%. The mitogenome has only one chromosomal structure, It contains 54 genes, including 31 protein-coding genes(PCG), 19 tRNA genes, and 4 rRNA genes. A total of 32 high-frequency codons exhibiting significant AT-bias, 431 RNA editing sites, and 26 homologous fragments were transferred from the chloroplast to mitochondria genes (7,337 bp, 1.68%). Furthermore, we conducted a phylogenetic analysis involving in A. lappa and 27 other taxa to clarify its evolutionary and taxonomic status. These findings provide a foundation for further understanding the evolutionary relationships within Asteraceae plant. CONCLUSION: Through the assembly and comprehensive analysis of A. lappa mitogenome, This study has for the first time fully elucidated its mitogenomic structural characteristics.These results not only provide high-quality genetic resources for research on the Asteraceae mitogenome but also lay a solid foundation for in-depth exploration of the evolution and functional genomics of medicinal plants in the Asteraceae family.

Genome, Mitochondrial↗
PubMed2026

T2T Genome Assembly and Multi-Omics Data Reveal Terrestrial Adaptation and Mucus Biosynthesis in Tropical Leatherleaf Slug (Laevicaulis alte).

Laevichaulis alte is a slug in the order Systellommatophora that evolved from aquatic ancestors and now faces strong challenges from desiccation, respiration on land, and novel pathogens. Its mucus is essential for water retention, locomotion, and defense. To link terrestrial adaptation with mucus biosynthesis, we generated a gap-free genome assembly of L. alte using PacBio HiFi reads, Oxford Nanopore ultra-long reads, and Hi-C data. The genome shows low heterozygosity and holocentromeric chromosomes. Functional metabolomics revealed marked metabolic shifts between L. alte and the closely related aquatic species Peronia verruculata. In L. alte, differential metabolites were enriched in lipid metabolism, immune regulation, and stress response pathways, consistent with life in a dry and microbe-rich terrestrial environment. Comparative genomics and transcriptomics identified candidate genes linked to mucus secretion and physiological adaptation, including VEGF, ASGR2, and COL6A6. Further analyses highlighted the vascular endothelial growth factor (VEGF) gene family as a key regulator connecting angiogenesis, tissue remodeling, and mucus production pathways in L. alte. Together, this gap-free genome and multi-omics dataset establish a molecular framework that links genomic innovation, mucus biology, and terrestrial adaptation in Systellommatophora, and they offer a basis for understanding ecological niche specialization in land molluscs.

Animals↗
PubMed2024

Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci.

The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in genomic disorders and cancer genomes, its architecture remains unresolved. Here, we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes. Using a combination of short-read genome sequencing (GS), long-read GS, optical genome mapping, and single-cell DNA template strand sequencing (strand-seq), the haplotype structure was resolved in 18 samples. The point of template switching in 4 samples was shown to be a segment of ∼2.2-5.5 kb of 100% nucleotide similarity within inverted repeat pairs. These data provide experimental evidence that inverted low-copy repeats act as recombinant substrates. This type of CGR can result in multiple conformers generating diverse SV haplotypes in susceptible dosage-sensitive loci.

Humans↗
PubMed2025

A chromosome-level genome assembly of Guimi No. 2 (Actinidia chinensis).

In this study, we report a high-quality chromosome-level genome assembly of Actinidia chinensis var. chinensis 'Guimi No. 2'. This cultivar, discovered in Guizhou karst ecosystems, exhibits resistance to Pseudomonas syringae pv. actinidiae (Psa). Using a combination of MGI short-read sequencing, PacBio HiFi long-read sequencing, and Hi-C technology, we generated a genome assembly of 608.43 Mb with a contig N50 of 20.70 Mb, and 99.70% of the assembly was successfully anchored onto 29 pseudochromosomes. The quality value (QV) and the LTR Assembly Index (LAI) of the assembled genome were 72.23 and 10.10. The BUSCO analysis indicated that the genome assembly and gene model prediction were 98.40% and 96.56% complete, respectively. A total of 251.15 Mb of repetitive sequences and 45,986 protein-coding genes were annotated. This genome assembly provides critical insights into A. chinensis's genomic architecture and serves as a foundational resource for elucidating disease resistance mechanisms against Psa, while enabling comparative phylogenomic studies across the Actinidia genus.

Actinidia↗
PubMed2025

Polygenic variants in DNA repair genes are associated with neurodevelopmental disorders, regression and increased burdens of somatic variants and short tandem repeat expansions.

PURPOSE: Developmental regression, characterized by the loss of acquired milestones, occurs in some individuals with neurodevelopmental disorders (NDDs); yet, its molecular basis remains unclear. Studies suggest that DNA damage repair (DDR) genes, such as FAN1, may protect against neurological dysfunction by modulating the somatic stability of short tandem repeats (STRs). This study explores the contribution of DDR gene variants in NDD cases presenting with regression. METHODS: We analyzed 1087 NDD patients, focusing on those carrying variants in DDR genes and presenting regression. We assessed the sensitivity to DNA damage using mitomycin C on lymphoblastoid cells. Somatic variants and STR expansions were evaluated through high-depth short-read genome sequencing. To further investigate the pathogenetic role of STR expansions, we performed long-read genome sequencing on the most severely affected proband. RESULTS: Probands with regression carried multiple DDR gene variants, several within the Fanconi anemia pathway. Their lymphoblastoid cells showed increased sensitivity to mitomycin C-induced cytotoxicity compared with parental and control samples. Probands with severe phenotypes and regression exhibited an accumulation of somatic variants and STR instability, enriched in neurodevelopmental genes. CONCLUSION: Our findings suggest that polygenic DDR gene variants may contribute to developmental regression in NDDs by promoting the accumulation of somatic variants and STR expansions.

Humans↗
PubMed2026

Beyond the gene: isoform diversity as a key contributor to human brain disorders.

The human brain exhibits exceptional transcriptomic complexity, with alternative splicing, promoter usage, and polyadenylation generating extensive transcript-isoform diversity. Isoform dysregulation is increasingly implicated in neurodevelopmental and psychiatric disorders (NPDs), yet the landscape, function, and genetic regulation of brain isoforms remain poorly understood due to limitations of short-read RNA sequencing. Advances in long-read sequencing (LR-seq) enable scalable full-length transcriptome profiling with single-cell and spatial resolution across developmental stages. Here, we review recent progress in isoform discovery, quantification, functional annotation, and genetic regulation, highlighting emerging links to human neurodevelopment and disease. LR-seq studies have uncovered tens of thousands of previously unannotated brain isoforms, with neuronal maturation characterized by increased exon inclusion and progressive 3' untranslated region (3' UTR) lengthening. Isoform-resolved genetic mapping outperforms gene-level analyses for NPD gene discovery and mechanistic interpretation. We argue that a shift from gene-centric to isoform-centric frameworks is essential to fully capture regulatory complexity in human neurogenetics. Together, these advances establish isoform diversity as a fundamental yet underappreciated axis of brain gene regulation and a key entry point for dissecting NPD biology.

Humans↗
PubMed2025

Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta.

The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goats in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Assembly using PacBio long-reads and Hi-C long-molecule scaffolding together with manual curation resulted in a 573 Mb assembly (N50 = 84 Mb, total scaffolds = 1,286) with five autosomal and one sex-linked chromosomal-scale scaffolds consistent with its karyotype. The genome resource was further improved via annotation of 22,948 genes, with manual curation of over 3,200 of these, resulting in a robust and near complete resource (96.3% complete protein BUSCOs) to support basic and applied research on this important veterinary pathogen. Genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes for benzimidazole, levamisole and ivermectin resistance, as well as novel regions associated with ivermectin and moxidectin resistance. These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance and identifying key loci to prioritise in developing diagnostic markers of anthelmintic resistance to support parasite control.

Animals↗