Search Results (896)

Karyotypic diversification in birds is often masked by overall chromosomal conservation, yet the mechanisms driving lineage-specific variation remain poorly understood. Here, we demonstrate that genome evolution in Rallidae is shaped by dynamic, independent trajectories of chromosomal reorganization, despite the retention of general avian architectural features. By integrating cytogenetic and molecular mapping data from two Neotropical species, Fulica rufifrons Philippi & Landbeck, 1861 (Red-fronted Coot) and Aramides ypecaha Vieillot, 1819 (Giant Wood Rail), we show that repetitive DNA expansion and heterochromatinization contribute to karyotype variability and sex chromosome differentiation. The contrasting structure and heterochromatic composition of the W chromosome between these species reveal that sex chromosomes evolve rapidly and independently, driven by lineage-specific accumulation of repetitive elements. Moreover, the variation in microsatellite distribution, especially the distinct localization of motifs on macro- and microchromosomes, underscores the independent and dynamic evolution of repetitive sequences. Our findings collectively indicate that chromosomal rearrangements, along with the amplification and redistribution of repetitive DNA, are contributing factors of genomic diversification in Rallidae, offering new insights into the mechanisms underlying karyotype evolution and sex chromosome differentiation in birds. Full article

Background: The litchi fruit borer, Conopomorpha sinensis (Lepidoptera: Gracillariidae), is a devastating pest affecting litchi and longan production across Asia. Although a reference mitochondrial genome (mitogenome) has been published, its utility is limited by the lack of precise geographical data and raw sequencing data. Methods: In this study, we sequenced and characterized the complete mitogenome of C. sinensis collected from Taiwan using a hybrid assembly of Illumina and Oxford Nanopore technologies. Results: The assembled mitogenome is 17,301 bp in length with a mean sequencing depth of 19,155-fold, comprising 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and an AT-rich control region. Notably, we identified a rare tRNA gene rearrangement (trnR-trnA-trnN-trnS1-trnE-trnF) that deviates from the ancestral lepidopteran ditrysian pattern. Comparative analysis revealed a 94.65% overall sequence identity with the reference mitogenome, though the PCGs remained highly conserved at 99.35%. Variant analysis demonstrated that this divergence is predominantly driven by structural variations (228 indels) rather than nucleotide substitutions (2 SNPs) across the entire mitogenome; furthermore, 94.7% of the indels were identified in the control region and intergenic spacers. Subtle differences in codon usage were also observed in the ND6 start codon (ATT vs. ATA) and COX1 stop codon (TAA vs. T). Phylogenetic and molecular clock analyses robustly clustered the Taiwan specimen within the C. sinensis clade. Molecular dating estimates that the Conopomorpha lineage originated during the Late Cretaceous (~77.23 Ma). Notably, the divergence between the Taiwan specimen and the reference lineage was estimated to be negligible (<0.01 Ma) within the protein-coding regions, demonstrating a high degree of purifying selection that maintains coding-sequence stability across geographically distinct specimens, even as substantial variation accumulates in non-coding genomic regions. Conclusions: These findings provide high-resolution genomic resources and a temporal framework for the evolutionary study of Gracillariidae, offering foundational tools for targeted pest management. Full article

Background: Acanthosomatidae (Hemiptera: Pentatomoidea), commonly known as parent bugs, is a comparatively small pentatomoid family whose biological distinctiveness is exemplified by the repeated evolution of maternal egg–nymph guarding in several lineages; however, mitogenomic data for this group remain limited. Acanthosoma murreeanum is an important representative of Acanthosoma, yet its complete mitochondrial genome and comparative mitogenomic characteristics have not been comprehensively studied. Methods: Here, we obtained the complete mitochondrial genome of A. murreeanum through sequencing, assembly, and annotation. We then characterized its mitogenomic structure, nucleotide composition, codon usage, RNA structural features, control-region organization, nucleotide diversity, evolutionary rates, and phylogenetic position. In addition, control-region characteristics were compared among available acanthosomatid mitogenomes to evaluate structural variation in the AT-rich region. Results: The sequenced mitochondrial genome of A. murreeanum is a circular molecule of 15,718 bp, comprising the standard set of 37 mitochondrial genes and a control region of 1104 bp. The genome exhibits a strong A + T bias (74.04%) and retains the typical mitochondrial gene order without gene rearrangement. Most protein-coding genes start with standard ATN codons, except COX1, which begins with TTG, whereas COX2 and ND5 terminate with incomplete stop codons. Most predicted tRNA genes displayed the conventional cloverleaf configuration, whereas trnS1 lacked a complete DHU arm and instead formed a simple loop. The control region was characterized by a 60 bp tandem-repeat unit and several conserved sequence motifs. Comparative analysis showed that control-region length, AT content, repeat-unit size, and motif composition varied among sampled Acanthosomatidae, while A. murreeanum and A. haemorrhoidale shared similar 60 bp tandem-repeat organization. Among the mitochondrial PCGs, ATP8 exhibited the highest level of variation, whereas COX1 was the most conserved. The Ka/Ks values of all genes were lower than 1, suggesting that these genes have evolved under purifying selection. Phylogenetic analyses based on maximum-likelihood and Bayesian-inference methods consistently supported a sister relationship between A. murreeanum and A. haemorrhoidale. Conclusions: This study provides a new mitogenomic resource for Acanthosomatidae and represents the first detailed comparative mitogenomic analysis within Acanthosoma. The results suggest that A. murreeanum retains a conserved mitochondrial genomic architecture, whereas variation in the AT-rich control region provides additional evidence for lineage-specific mitogenomic differentiation. These results provide useful insights into mitogenome evolution and phylogenetic relationships within Acanthosoma and closely related acanthosomatid groups. Full article

Over the past decade, the growth of Helicobacter pylori antibiotic resistance has had an increasingly significant impact on the choice of eradication therapy regimens, significantly limiting the number of effective treatment options. The Maastricht VI guidelines consider the use of probiotics as one way to optimise therapy and increase the likelihood of successful eradication. In this regard, the study of the possible mechanisms of action of probiotic preparations on antibiotic-resistant strains of H. pylori, as well as their possible role in preventing the development of resistance, is of considerable interest and may contribute to improving the quality of eradication therapy in the near future. The aim of the study is to determine the role of probiotics in modifying the microbiota during and after eradication therapy, as well as to assess their potential impact on the development of antibiotic resistance. A search for scientific publications was conducted in international and national bibliographic databases: PubMed, Embase, Scopus, Web of Science Core Collection, Google Scholar, and eLIBRARY.ru. The search was conducted in English, Russian, and Kazakh for the period from 26 April 2015 to 14 July 2025. The review includes 41 publications. Eradication therapy has a pronounced negative effect on the intestinal microbiota, leading to disruption of its composition and the development of side effects that reduce treatment tolerability. A number of studies in recent years have demonstrated a link between antibiotic therapy and the development of antibiotic resistance caused by genetic rearrangements and mutations in the gut microbiota genome. As an additional approach to correcting these adverse effects, special attention is paid to the use of probiotics. According to the research results, probiotic preparations help reduce the frequency of side effects of eradication therapy and may increase its effectiveness against antibiotic-resistant strains of H. pylori. The use of probiotic preparations in the treatment of resistant strains of Helicobacter pylori is a promising direction that opens up new opportunities for optimising eradication regimens. However, this approach requires further clinical and experimental studies to confirm its effectiveness and form reasonable prognostic conclusions. Full article

Acute lymphoblastic leukemia (ALL) is a genetically and epigenetically heterogeneous malignant disease characterized by different subtypes with varying sensitivities to conventional chemotherapy. Despite significant improvements in survival rates, relapse remains the primary cause of treatment failure, often associated with intrinsic or acquired drug resistance. First-line therapy at diagnosis represents a major determinant of relapse in ALL. In this study, we performed a transcriptome and drug response profiling analysis to identify subtype-specific cell surface proteins that are overexpressed in patients with poor response to induction therapy. We summarize the current state of knowledge regarding chemotherapy responses, resistance mechanisms to standard cytostatic drugs and the increasing importance of cell biomarkers as predictors of an adverse disease course and potential therapeutic targets. We discuss the results of clinical and molecular studies linking specific genomic alterations—such as KMT2A-rearrangements, Ph-like, DUX4-rearrangements and T-ALL—to drug resistance and highlight surface antigens like CSPG4, HER2, MCAM and ROR1 that define high-risk leukemia phenotypes. The integration of transcriptomic, immunophenotypic and drug response data could enable a new generation of risk-adapted, surface-directed strategies for relapse treatment in ALL. Our analysis therefore provides subtype-specific predictive therapeutic targets for relapse treatment in ALL. Full article

Large genomic rearrangements (LGRs), occurring as copy number alterations (CNAs), represent a clinically relevant class of pathogenic or likely pathogenic variants (P LPVs) in BRCA1/2 (BRCA) genes in ovarian cancer (OC). We evaluated the performance of a high-resolution algorithm integrated into a commercial homologous recombination deficiency (HRD) assay to improve the identification of clinically actionable CNAs in BRCA genes by formalin-fixed paraffin-embedded (FFPE) samples. A total of 760 OC samples were analyzed using a commercial HRD assay incorporating a bioinformatics algorithm for CNA detection. The algorithm was additionally applied to additional homologous recombination repair (HRR) genes, and associations between CNA events and genomic instability (GI) were evaluated. The algorithm demonstrated high sensitivity for both gene and exon-level CNA. The high correlation between CNA positivity cases and GI, in the absence of P/LPVs BRCA single-nucleotide or indels variants, emphasizes the value of integrating CNA detection into routine HRD testing workflows. The extended analysis of additional HRR genes enabled broader characterization of clinically relevant CNAs. This study enables reliable identification of clinically relevant BRCA LGRs from FFPE within HRD testing, supporting a tumor-first diagnostic strategy. This approach may expand the identification of OC patients potentially eligible for PARP inhibitor therapy. Full article

The emergence of pangenome graphs represents a paradigm shift in genomics, moving beyond linear reference genomes to embrace the full spectrum of genetic diversity within and across species. These graph-based models provide a unified framework for representing alternative haplotypes, structural variants, and complex genomic rearrangements that are often missed by traditional approaches. This paper reviews the latest developments in pangenome graph construction, data structures, alignment algorithms, and variant inference. We explore recent human, plant, and microbial genomics applications, highlighting the advantages of graph representations in capturing population diversity and improving read mapping accuracy. We briefly discuss emerging directions such as machine learning-assisted graph analysis, although current applications remain limited and exploratory. Furthermore, we examine the emerging field of clinical genomics, where pangenome references have demonstrated measurable improvements in diagnostic yield—specifically increasing variant calling sensitivity for complex structural variants by up to 10–40% compared to linear models. We conclude by addressing ongoing challenges in graph scalability and standardization, aiming to guide future research and implementation in this rapidly evolving field. Full article

Introduction: Soft tissue sarcomas (STS) exhibit profound molecular heterogeneity. While recurrent gene fusions hold significant diagnostic and therapeutic value—guiding treatment selection and identifying novel molecular targets—our understanding of their broader clinical implications remains limited. Materials and Methods: We performed next-generation sequencing (NGS; FusionPlex Sarcoma v2, Archer™) and bioinformatic analysis (STAR v.2.7, Arriba) on formalin-fixed paraffin-embedded (FFPE) core needle biopsy specimens. The cohort consisted of patients enrolled in a phase II clinical trial (NCT03651375) who received preoperative chemoradiotherapy according to the UNRESARC protocol. Results: The analysed cohort comprised nine adult patients (median age 66 years; range 44–73) diagnosed with undifferentiated pleomorphic sarcoma (UPS; n = 3), malignant peripheral nerve sheath tumour (MPNST; n = 3), myxofibrosarcoma (MFS; n = 2), and leiomyosarcoma (LMS; n = 1), predominantly high-grade (G3; 5/9) and extremity-localised (6/9). Gene fusions were detected in one-third of patients (3/9), exclusively in G3 tumours. Specifically, we identified an SGSH-PRKCA fusion in MFS (thigh), a LINC01133-OGA fusion in MPNST (thorax), and a concurrent JAZF1-MYH7B (chr7:27995037 intronic-chr20:33563203 exon/splice-site, out-of-frame but preserving myosin domains) with a PRKCA-associated intergenic rearrangement (chr1, retaining C1/kinase domains) in UPS (upper back). Notably, the SGSH-PRKCA and JAZF1-MYH7B pairs have not been previously described in the literature for these STS subtypes. Fusion-positive (F1) cases showed stable radiological disease (RECIST 1.1 SD) and EORTC C/D pathological responses with 5–20% residual viable tumour, whereas fusion-negative (F0) cases showed a wider range of radiological and pathological outcomes, including partial response, progression, and stable disease. Conclusions: Our analysis suggests that broad genomic profiling may provide complementary molecular information in diagnostically challenging cases managed at specialised sarcoma centres, particularly when morphology and immunohistochemistry are insufficient. In the present series, however, the detected rearrangements did not alter systemic treatment, and the data do not support claims of prognostic, predictive, or therapeutic actionability. Full article

The immunoglobulins (IG) or antibodies and the T cell receptors (TR) are the antigen receptors of the adaptive immune responses (AIR) of jawed vertebrates (Gnathostomata). IMGT^®, the international ImMunoGeneTics information system^®, was created in 1989 by Marie-Paule Lefranc (Laboratoire d’ImmunoGénétique Moléculaire (LIGM), Université de Montpellier and CNRS) to deal with and to manage the huge diversity of IG or antibodies and TR. The founding of IMGT^® marked the advent of immunoinformatics, a new science which emerged at the interface between immunogenetics and bioinformatics. For the first time, the IG and TR variable (V), diversity (D), joining (J) and constant (C) genes were officially recognized as ‘genes’, as were the conventional genes. The IMGT-ONTOLOGY CLASSIFICATION axiom and the concepts of classification have generated the IMGT nomenclature and the IMGT Scientific chart rules for assigning IMGT names to IG and TR genes and alleles of Homo sapiens and of any other jawed vertebrate species. The IMGT nomenclature is used for genes in locus, in sequences (genomic or rearranged, expressed or not) and in structures enabling comparative immunology, evolutionary immunogenetics, standardized analysis and comparison of IG and TR repertoires analysis in normal or pathologic situations. IMGT nomenclature is used in basic, veterinary, and medical research, in clinical applications (mutation analysis in leukemia and lymphoma), and in therapeutic antibody design, engineering and humanization. By providing consistent and high standard biocuration for the description of the IG and TR loci, genes and alleles, and for the analysis of the IG or antibody and TR-expressed rearranged sequences and proteins and structures, the IMGT nomenclature is the common language for immunoinformatics and artificial intelligence (AI). Full article

Members of the genus Rhizobium are best known for nitrogen-fixing symbioses with legumes, yet their diversity and evolutionary roles in non-legume hosts remain poorly explored, particularly in arid ecosystems. We report the isolation and characterization of strain AGC32, an endophytic bacterium obtained from surface-sterilized roots of the desert medicinal plant Peganum harmala collected in Moroccan drylands. Phylogenomic analyses placed AGC32 within the genus Rhizobium but clearly distinct from described species, with average nucleotide identity values below 96% and digital DNA–DNA hybridization values below 70%, supporting its designation as a novel species for which the name Rhizobium moroccans sp. nov. is proposed. Comparative genomics revealed extensive structural genome rearrangements relative to its closest sequenced relative, Rhizobium deserti, indicating a divergent evolutionary trajectory. The high-quality draft genome encodes metabolic pathways associated with adaptation to nutrient limitation and environmental stress, including complete allantoin utilization, polyphosphate metabolism, organic acid assimilation, and multiple systems involved in oxidative and osmotic stress tolerance. Phenotypic assays corroborated these genomic predictions, demonstrating the ability to metabolize diverse organic acids and carbohydrates and to express multiple plant growth–promoting traits, including nitrogen fixation and the solubilization of phosphorus, potassium, and silicon. Collectively, these findings expand the ecological and evolutionary diversity of Rhizobium, demonstrate its capacity to associate with non-legume medicinal plants in extreme environments, and highlight desert ecosystems as reservoirs of previously unrecognized microbial diversity with potential applications in sustainable agriculture in arid regions. Full article

G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in gene regulation and genome stability. Among them, the telomeric repeat-containing RNA (TERRA) forms biologically relevant RNA G4s (rG4s) that participate in telomere maintenance and genome stability. Although many ligands targeting DNA G4s have been reported, the recognition and modulation of RNA G4 topologies remain less explored. In this work, we investigated the interaction between TERRA and the spermine-functionalized Zn(II) porphyrin, ZnTCPPSpm4, using UV–vis absorption, fluorescence, resonance light scattering (RLS), and circular dichroism (CD) spectroscopy. In K⁺, where TERRA adopts a parallel G4 conformation, ZnTCPPSpm4 binds through a stepwise mechanism involving external end-stacking, forming discrete supramolecular complexes without altering the native topology. In contrast, under Na⁺ conditions, ZnTCPPSpm4 induces a gradual conformational rearrangement of TERRA from the antiparallel to a parallel-like G4 topology. A CD melting study showed that ZnTCPPSpm4 stabilizes the parallel RNA G4, while slightly destabilizing the antiparallel topology. Overall, our results demonstrate that ZnTCPPSpm4 is not a simple G4 binder, but a topology-selective ligand capable of remodeling TERRA G4 structures, highlighting the potential of metalloporphyrins as RNA G4-targeting scaffolds. Full article

Armillaria species hold significant ecological and economic importance and they play a vital role in the growth of traditional Chinese medicine Gastrodia elata (G. elata). In this study, we assembled and compared the mitochondrial genomes (mitogenomes) of six Armillaria mellea (Vahl) P. Kumm. (A. mellea) strains isolated from the main G. elata-producing region of Hanzhong, China. The internal transcribed spacer (ITS) sequencing confirmed that all six strains form a monophyletic clade. Their mitogenomes (120,775 to 120,839 bp) exhibit a highly conserved architecture, each containing 16 protein-coding genes (PCGs), 23 open reading frames (ORFs), 27 tRNAs, and two rRNAs. Codon usage and amino acid frequency were strikingly similar among the six strains, with a strong AT bias. In contrast, comparisons with other Armillaria species revealed marked differences in gene order, repeat structures, and selection pressures. Phylogenetic analyses based on PCGs further resolved the close relationship among the six strains while highlighting distinct molecular variation across species. On the whole, these findings demonstrate that A. mellea strains co-evolving with G. elata maintain a highly uniform mitochondrial genome architecture, suggesting strong purifying selection or recent divergence within this symbiotic population. The pronounced differences from other Armillaria species at the levels of gene arrangement and selection pressure imply that mitochondrial gene rearrangement may have accompanied species diversification in the genus. By providing the first complete mitogenomes of A. mellea from a major G. elata cultivation area, this study not only expands the genomic resources for Armillaria but also establishes a foundation for understanding how mitochondrial variation might influence fungal growth, adaptation, and symbiotic efficiency with G. elata. Full article

Recombinogenic DNA damage can initiate chromosomal rearrangements that can alter gene expression or accelerate cancer progression in higher eukaryotes. Thus, there is a critical need to identify genes that suppress chromosomal rearrangements and environmental exposures that promote genetic instability. Cell cycle checkpoints modulate the cell cycle so that DNA repair occurs before the replication or segregation of damaged chromosomes. Saccharomyces cerevisiae (budding yeast) RAD9 was the first cell cycle checkpoint gene identified, which initiated intensive research studies into the mechanisms of checkpoint activation and the phenotypes of checkpoint mutants. The budding yeast Rad9 protein serves as both an adaptor and scaffold that facilitates downstream effector activation to orchestrate a DNA damage response at multiple stages of the cell cycle, which facilitates double-strand break (DSB) repair by sister chromatid recombination. However, the role of RAD9 in homologous recombination and in suppressing gross chromosomal rearrangements (GCRs) is not completely understood. In this review we discuss how RAD9 can promote genome instability resulting from aberrant DNA replication intermediates, while suppressing DSB-associated rearrangements. We also discuss possible mechanisms accounting for the synergistic increase in genomic instability in double mutants defective in both RAD9 and recombinational repair. We emphasize that while there is an overlap between checkpoint and recombinational repair pathways, RAD9 and checkpoint pathways can function independently to suppress chromosomal instability. These studies thus elucidate checkpoint mechanisms that control homologous recombination between repeated sequences. Full article

Pedicularis henryi is a hemiparasitic species within Orobanchaceae (Lamiales). In this study, the mitochondrial genome of P. henryi was assembled and characterized. The mitogenome is 251,317 bp in length with a GC content of 44.32%, containing 36 protein-coding genes, 24 tRNAs, and three rRNAs. Codon usage analysis revealed a marked preference for A/U-terminated codons. A total of 196 repetitive elements were identified, with interspersed repeats as the most abundant type. We detected 293 C-to-U RNA editing sites across 31 protein-coding genes, predominantly causing non-synonymous substitutions. Eighteen chloroplast-derived fragments totaling 35,894 bp were found, accounting for 15.0% of the mitogenome. Nucleotide diversity analysis among three Pedicularis species showed an average π of 0.0018, with core respiratory genes highly conserved. Synteny analysis revealed extensive structural rearrangement in P. henryi compared to P. chinensis. This study provides mitochondrial genomic resources for Orobanchaceae and insights into mitogenome evolution in hemiparasitic plants. Full article

This study investigated the in vitro replication kinetics and molecular characteristics of five field isolates of bovine viral diarrhea virus (BVDV) representing subgenotypes 1b, 1d, and 1f, currently circulating in Hungary. We compared cytopathogenic (cp) and non-cytopathogenic (ncp) biotype pairs using digital PCR (dPCR) and virus titration. While dPCR showed higher genome copy numbers for cp isolates, virus titration revealed comparable or lower infectious titers, suggesting the accumulation of replication-incompetent viral particles during the infection cycle. Molecular analysis identified (novel) amino acid substitutions in Npro, capsid, and NS4B regions, although typical large-scale genome rearrangements were absent. These findings demonstrate that biotype differences are molecularly complex and subgenotype-dependent. Our results emphasize that relying on a few genetic markers is insufficient for biotype categorization, necessitating comprehensive characterization in BVDV surveillance programs. This complexity must be considered when designing vaccines or control programs, especially in regions with diverse circulating strains. Full article