Mol. Genet. Genomics [JOURNAL]
Sun
200 papers
Northeast india: genetic inconsistency across ethnicity and geography.
Bankura B, Basak B, Singh PP … +7 more , Vanlalruata A, Chatterjee A, Chatterjee S, Tamang R, Hazarika M, Chaubey G, Das M
Mol Genet Genomics · 2026 Jan · PMID 41619049 · Publisher ↗
North East India served as a crucial route for the movement of modern humans, connecting the Indian subcontinent with East and Southeast Asia due to its strategic location near the Himalayas and the Bay of Bengal. Archae...
North East India served as a crucial route for the movement of modern humans, connecting the Indian subcontinent with East and Southeast Asia due to its strategic location near the Himalayas and the Bay of Bengal. Archaeological and anthropological research indicates migration and cultural exchange in this region, along with the Tibetan plateau to the north. To understand the complex genetic patterns here, we conducted a detailed analysis of the Mizo population and its various clans in North-East India, a unique and independent group for which genomic historical records are currently unavailable. We examined 110 individuals from seven different Mizo clans using one hundred thousand autosomal markers (Sequence data accession number EGAS00001008205). Our haplotype-based analysis revealed that the Mizo people belong to the same clade as the Trans-Himalayan group, suggesting a common origin from a shared ancestral population. Additionally, our study identified seven genetic clusters among the Mizo clans, with many clans spanning more than one cluster; notably, a distinct population structure was evident even across small geographical distances. The results also show that the Mizo genetic profile differs from that of East and Southeast Asian populations. Allelic frequency-based analyses indicated that a novel Trans-Himalayan ancestry unites all the populations of this region. The findings suggest a complex genetic structure in North-East India, which contrasts sharply with the genetic landscape observed in East and South-East Asia. Therefore, we conclude that the interplay of language, ethnicity, and geography shapes the genetic makeup of the Mizo population and its clans.
In vitro assessment of siRNA-mediated LRP5 silencing and temozolomide treatment in glioblastoma and brain cancer stem cells.
Kucuk A, Caglar HO, Karatas OF … +2 more , Biray Avci C, Gunduz C
Mol Genet Genomics · 2026 Jan · PMID 41619048 · Publisher ↗
Low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor of frizzled (FZD) in the WNT/β-catenin signaling pathway, recognizes Wnt ligands. This study aimed to assess the anti-cancer effects of silencing L...
Low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor of frizzled (FZD) in the WNT/β-catenin signaling pathway, recognizes Wnt ligands. This study aimed to assess the anti-cancer effects of silencing LRP5 on glioblastoma (GBM) and brain cancer stem cells (BCSCs). Additionally, the effect of temozolomide (TMZ) was also examined in these cells with suppressed LRP5 expression. LRP5 expression was silenced in U87MG, T98G, and BCSC cells using siRNA. Protein expression levels were determined by Western blotting. Cell viability after LRP5 silencing and/or TMZ treatment was evaluated using the CVDK-8 assay. Flow cytometry was used to examine apoptosis and cell cycle progression. Clonogenic, cell invasion, and wound-healing assays were used to assess colony formation, invasion, and migration, respectively. siRNA-mediated silencing reduced protein expression of LRP5 and Wnt/β-catenin target genes in GBM and BCSC cells. Furthermore, suppression of LRP5 reduced cell viability, and its combination with TMZ enhanced anti-proliferative effects. Silencing LRP5 and/or TMZ treatment caused cell cycle arrest and significantly diminished the aggressive characteristics of GBM and BCSC cells. These findings suggest that LRP5 may serve as a potential therapeutic target for treating GBM. Targeting LRP5 may enhance the effectiveness of the chemotherapy agent TMZ in GBM.
Exploring the genetic landscape of sesame: whole genome sequencing reveals distinct Egyptian lineages and SNP variability.
Azzam CR, Arafa RA, Ahmed MZS … +5 more , Ibrahim SD, Rizk MS, Saedwi AM, Shirasawa K, Alsamman AM
Mol Genet Genomics · 2026 Jan · PMID 41619030 · Publisher ↗
Sesame, one of the earliest cultivated oil crops in human history, holds a distinguished place due to its high oil content, rich flavor, and distinctive nutty aroma. In this study, we performed whole-genome resequencing...
Sesame, one of the earliest cultivated oil crops in human history, holds a distinguished place due to its high oil content, rich flavor, and distinctive nutty aroma. In this study, we performed whole-genome resequencing on five Egyptian sesame genotypes (Shandaweel 3, Toshky1, and three gamma-irradiated mutant lines). Additionally, we incorporated 19 publicly available sesame genome datasets from the NCBI Sequence Read Archive (SRA) to support comparative genomic analyses. We identified 6,106,085 nucleotide variants across the 24 sesame genotypes studied. After excluding low-coverage SNPs, we obtained 26,424 SNPs with MAF > 0.05 used for subsequent analysis. The highest number of SNPs was observed on Chromosome Si01 (4144 SNPs), followed by Si12 (3721 SNPs) and Si13 (3151 SNPs), whereas Si09 (241 SNPs) and Si02 (359 SNPs) displayed the lowest SNP counts. Genome-wide diversity analysis revealed variation across chromosomes, with chromosomes Si04 and Si07 showing the highest heterozygosity (Ho = 0.816-0.849) and polymorphism information content (PIC = 0.347-0.353). Population structure analysis identified three distinct genetic clusters, with Egyptian cultivars forming a genetically pure and separate cluster.Chinese cultivars showed admixture with those from the USA and South Korea. Phylogenetic analysis supported the country-based clustering, with Egyptian genotypes forming a unique group. SNP effect analysis showed that missense mutations were common, potentially affecting protein function. Notable impacted genes included AXR1, CYP73A5, and CERK1, which play critical roles in growth, stress resilience, and pathogen defense. By integrating public RNA-seq datasets with our genomic variant data, we explored the correlation between gene expression and genetic variation. This multi-omics analysis identified genes with variants and expression patterns potentially involved in stress adaptation, including membrane stabilizers (UGT80B1, CalS10), signaling regulators (PUB9, CNGC15b), hormonal integrators (ARF2, DLO1), and redox managers. Our whole-genome sequencing study highlights the influence of geographic origin on sesame genetic diversity and provides SNP data for breeding programs aimed at enhancing adaptability and resilience.
Impairment of ribosomes and DNA biosynthesis confers resistance to Inhibition of sphingolipid biosynthesis.
Yamagata S, Sugihara S, Kawaguchi T … +3 more , Matsuzaki M, Tabuchi M, Tani M
Mol Genet Genomics · 2026 Jan · PMID 41619027 · Publisher ↗
Sphingolipids are essential components of eukaryotic membranes and play central roles in cellular growth and stress responses. In the budding yeast Saccharomyces cerevisiae, Lcb1 and Lcb2 constitute the serine palmitoylt...
Sphingolipids are essential components of eukaryotic membranes and play central roles in cellular growth and stress responses. In the budding yeast Saccharomyces cerevisiae, Lcb1 and Lcb2 constitute the serine palmitoyltransferase complex, which catalyzes the initial step of sphingolipid biosynthesis. Repression of LCB1 expression leads to inhibition of sphingolipid biosynthesis, resulting in severe growth defects. Here, we aimed to identify novel genes functionally associated with sphingolipid metabolism by screening for suppressor mutations that confer resistance to sphingolipid biosynthesis inhibition. To conditionally suppress sphingolipid biosynthesis, we employed a tetracycline-repressible promoter to control LCB1 expression. This screen revealed that deletion of SAC7, YTA7, RNR1, RPL23B, or RPL35A confers resistance to LCB1 repression. The suppressive effect of YTA7, RNR1, RPL23B, and RPL35A deletions was also observed under conditions in which growth inhibition was induced by repression of AUR1, a gene involved in the conversion of ceramides to complex sphingolipids. These genes encode proteins related to ribosomal subunits or DNA biosynthesis. Furthermore, sublethal concentrations of cycloheximide (a translation inhibitor), diazaborine (a ribosome maturation inhibitor), hydroxyurea (a DNA biosynthesis inhibitor), and zeocin (a DNA double-strand break inducer) alleviated growth defects caused by LCB1 repression. Diazaborine or hydroxyurea partly suppressed the decrease in complex sphingolipids induced by Lcb1 repression. Additionally, these treatments suppressed the reduction in Lcb1 and Aur1 protein expression levels. These findings reveal a previously unappreciated link between ribosome function, DNA biosynthesis, and sphingolipid metabolism and provide insight into how cells adapt to metabolic stress.
Mitochondrial genomes of Mentha reveal structural complexity and evolutionary diversity.
Shao BY, Liu SJ, Zhang TQ … +1 more , Xue JY
Mol Genet Genomics · 2026 Jan · PMID 41619003 · Publisher ↗
Mitochondrial genomes play essential roles in plant energy metabolism and evolution, yet their structural complexity and diversity in plants remain poorly understood. This study aims to address the question by analyzing...
Mitochondrial genomes play essential roles in plant energy metabolism and evolution, yet their structural complexity and diversity in plants remain poorly understood. This study aims to address the question by analyzing four newly assembled Mentha mitochondrial genomes (M. longifolia, M. suaveolens, M. pulegium, and M. requienii), which serve as valuable genomic resources for phylogenetic and evolutionary studies. Comparative analyses revealed structural diversity, codon usage bias, extensive RNA editing, and abundant repetitive sequences driving genomic rearrangements in the four mitochondrial genomes. Chloroplast-derived DNA fragments were dynamically integrated into the four Mentha mitochondrial genomes, highlighting ongoing interorganellar DNA transfer between plastids and mitochondria. Phylogenetic reconstructions based on mitochondrial, nuclear, and chloroplast genomes exhibit considerable discordance, reflecting complex evolutionary processes such as hybridization, introgression, and allopolyploidization within the genus. In conclusion, the structural diversity, codon usage bias, and ongoing interorganellar DNA transfer observed in Mentha mitochondrial genomes underscore their dynamic evolutionary nature. The discordance among mitochondrial, plastid, and nuclear phylogenies reflects complex evolutionary processes (possibly hybridization and allo-polyplodization) of Mentha species. These findings enhance the understanding of the mechanisms underlying the complexity and diversity of Mentha species and provide broader insights into the evolution of plant mitochondrial genomes.
Buparlisib induces eukaryotic elongation factor-2 expression to cause treatment failure for lung cancer cells.
Wang D, Su C, Zhang X … +4 more , Mao W, Dai X, Xu L, Si X
Mol Genet Genomics · 2026 Jan · PMID 41619002 · Publisher ↗
BACKGROUND: The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is closely associated with the development and progression of lung cancer. Buparlisib (BKM‑12...
BACKGROUND: The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is closely associated with the development and progression of lung cancer. Buparlisib (BKM‑120), a selective PI3K inhibitor, represents a novel potential therapeutic strategy for lung cancer. However, the reason for its limited initial efficacy as a monotherapy remains poorly understood. This study aims to systematically elucidate the key molecular mechanisms underlying the inefficacy of Buparlisib in lung cancer cells and to identify the core regulatory factors and signaling pathways involved. METHODS: A549 lung cancer cells served as the primary model, along with clinical lung cancer tissue samples and nude mouse subcutaneous xenograft models. Techniques including immunohistochemistry, Western blot, flow cytometry, eukaryotic elongation factor‑2 (EEF2) knockdown (short hairpin RNA targeting EEF2 [sh‑EEF2]), Cell Counting Kit‑8 cell proliferation assays, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis analysis were used to investigate changes in the PI3K/AKT/mTOR‑EEF2 kinase (EEF2K)‑EEF2 pathway after Buparlisib treatment, to examine the relationship between reactive oxygen species (ROS) and EEF2 expression, and to evaluate the regulatory role of EEF2 in the anti‑lung‑cancer effects of Buparlisib. RESULTS: PI3K, EEF2K, and EEF2 were highly expressed in lung cancer tissues. Buparlisib effectively inhibited the activity of the PI3K/AKT/mTOR pathway in A549 cells, reduced EEF2K phosphorylation levels, and simultaneously significantly upregulated EEF2 protein expression (without altering its non‑phosphorylated state). EEF2 expression was highly sensitive to changes in ROS levels. Following EEF2 knockdown, the inhibitory effect of Buparlisib on A549 cell proliferation was significantly enhanced, and the apoptosis rate increased markedly. Animal experiments further confirmed that limiting EEF2 expression significantly improved the therapeutic efficacy of Buparlisib against lung cancer xenografts. CONCLUSION: Buparlisib regulates EEF2 through a dual mechanism: directly inhibiting the PI3K/AKT/mTOR‑EEF2K pathway, thereby activating EEF2, and inducing ROS to upregulate EEF2 expression. These combined actions enhance the anti‑apoptotic function of EEF2, thereby compromising the anti‑tumor effects of Buparlisib. This study provides a new direction for optimizing PI3K inhibitor‑based treatment strategies in clinical practice.
Cell-free DNA in chemical carcinogen induced mouse lung cancer and colon cancer model: its implications in diagnostics and therapeutics.
Trivedi DD, Shaikh AM, Patel SK … +2 more , Dalai SK, Bakshi SR
Mol Genet Genomics · 2026 Jan · PMID 41618999 · Publisher ↗
Chemical carcinogen induced mouse models closely mimic environmentally driven human cancers and provide platforms for studying tumor initiation and progression. However, the behavior and diagnostic value of cell-free DNA...
Chemical carcinogen induced mouse models closely mimic environmentally driven human cancers and provide platforms for studying tumor initiation and progression. However, the behavior and diagnostic value of cell-free DNA (cfDNA) in such models remain poorly understood, limiting their translational utility for biomarker development. Considering the increasing clinical relevance of cfDNA for early detection and treatment monitoring, this study aimed to systematically characterize cfDNA dynamics and genomic alterations in B(a)P induced lung cancer and DMH induced colon cancer mouse models. The aim was to evaluate cfDNA as a minimally invasive biomarker that reflects tumor burden and its potential use in preclinical diagnostic and therapeutic studies. Mouse lung and colon cancers were induced using B(a)P and DMH, respectively. Plasma was collected at defined time points, cfDNA was isolated, quantified, and analyzed for integrity profiles. Real time assessment was performed using liquid biopsies of cell free DNA using NGS-WGS platform for non-invasive tumor detection in live animals, reserving histopathology for post-mortem analysis. Our results reveal circulating cell-free DNA mutations similar to those found in humans (Lung cancer: ALK, NRAS, NF1, BRAF, FGFR1OP, FGFR1, STK11ip, AKT1 & AK1S1; Colon cancer: APC, MYC, KRAS). We have performed gene enrichment and protein-protein interactions and found various cancer related genes. The histopathological examination revealed neoplastic changes that corroborated with genomic studies. This study establishes cfDNA as a potential surrogate biomarker in chemical carcinogen induced lung and colon cancer models, supporting its utility for early detection, disease monitoring, and preclinical therapeutic assessment.
A combined computational and functional approach identifies FBLN5 as an amino acid metabolism-related gene and suppressing colorectal cancer progression.
Chen J, Bai Y, Liu S … +1 more , Lin C
Mol Genet Genomics · 2026 Jan · PMID 41618991 · Publisher ↗
The importance of amino acid metabolism in regulating cancers progression was investigated by accumulating research. But the role of amino acid metabolism-related genes (AAMRGs) played in the colorectal cancer (CRC) prog...
The importance of amino acid metabolism in regulating cancers progression was investigated by accumulating research. But the role of amino acid metabolism-related genes (AAMRGs) played in the colorectal cancer (CRC) progression remains unclear. We used Cox-LASSO analysis to construct an AAMRG prognostic signature and performed Gene set enrichment analysis (GSEA) for further investigation. Moreover, RT‒qPCR was adopted to estimate the expression of AAMRGs in clinical samples. Cell-based assays, including CCK-8, colony formation, and transwell assays were also performed to identify the roles of fibulin 5 (FBLN5) in CRC progression. We established a 10-AAMRG prognostic signature and stratified CRC samples into two risk groups, which showed significant differences in immune infiltration and EMT. RT-qPCR and human protein atlas data confirmed the mRNA and protein expression of these 10 AAMRGs, validating our bioinformatics findings. Importantly, functional assays revealed that FBLN5 overexpression suppressed CRC cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo. Our study establishes a novel 10-AAMRG signature as a promising predictor of therapeutic response and prognosis in CRC, and we identify FBLN5 as a pivotal protective factor in CRC progression, offering potential therapeutic value for targeted interventions.
Comparative and phylogenomic analysis of Eikenella genus suggest taxonomic reclassification of Eikenella corrodens strain KCOM 3110 as novel species and reveals unique CE1 carbohydrate-active enzyme family.
Suresh R, Jayachandiran S, Balu P … +1 more , Ramasamy D
Mol Genet Genomics · 2026 Jan · PMID 41559493 · Publisher ↗
The Eikenella genus includes opportunistic pathogens of clinical importance, commonly associated with infections such as endocarditis, periodontitis, wound abscesses, and respiratory tract infections; however, its taxono...
The Eikenella genus includes opportunistic pathogens of clinical importance, commonly associated with infections such as endocarditis, periodontitis, wound abscesses, and respiratory tract infections; however, its taxonomy, genetic diversity, and evolutionary relationships remain poorly understood. This study aims to clarify the genomic diversity and taxonomic boundaries within the genus through comprehensive comparative and phylogenomic analyses. We conducted a genomic comparison of 63 Eikenella genomes, including 35 high-quality drafts and 5 complete genomes, to understand their phylogenetic relationships and identify potential taxonomic misclassifications. Notably, Eikenella corrodens strain KCOM 3110 had the largest genome (2.46 Mb), the highest number of CDSs (2,877), and carried 611 unique genes among complete Eikenella strains. Phylogenetic trees based on 16S rRNA and whole genome data showed that KCOM 3110 did not cluster with the Eikenella corrodens group, but was closer to Eikenella halliae. The average nucleotide identity (~ 93%) and digital DNA-DNA Hybridization (~ 51.7%) values with Eikenella corrodens were below the species-level thresholds. Importantly, unique genes for antimicrobial resistance, metal tolerance, phage functions, and a distinct CE1 CAZyme profile supported its novelty. Overall, these findings indicate that Eikenella corrodens strain KCOM 3110 represents a novel species within the Eikenella genus. The study highlights the power of genome-based approaches in resolving bacterial taxonomy. It provides new insights into the evolutionary and functional diversity of Eikenella while laying the foundation for future studies on the ecological role, pathogenic potential, and clinical significance of this novel species.
Flemboda artificial intelligence: hybrid fuzzy-convolutional neural network for efficient chromosome abnormality classification.
Kiruthika K, Sarumathi S, Karpagam M … +1 more , Kaviarasu K
Mol Genet Genomics · 2026 Jan · PMID 41559480 · Publisher ↗
Chromosomal abnormality detection is a fundamental task in clinical genetics, as accurate identification of structural and numerical defects is essential for reliable diagnosis and treatment planning. However, many exist...
Chromosomal abnormality detection is a fundamental task in clinical genetics, as accurate identification of structural and numerical defects is essential for reliable diagnosis and treatment planning. However, many existing learning-based approaches failed to effectively capture diverse discriminative features, limiting their classification performance. To address this challenge, this study proposes FLEMBODA AI, an advanced computational framework designed to enhance the efficiency, accuracy, and robustness of automated chromosome defect detection. At first, the karyotype image is collected. Then, the input is augmented and pre-processed using normalization and a G-bending enhancement approach to ensure that the model's effectiveness generalizes across diverse datasets. After that, the chromosomes are segmented from the pre-processed image using a U-Net approach to isolate chromosomes from the karyotype image. Then, the segmented chromosomes are given as input to the Hybrid Fuzzy-Convolutional Neural Network (Hybrid Fuzzy-CNN) approach. In this, the CNN model performs the Feature Extraction (FE) process, and the Fuzzy logic is used for the classification of chromosomal abnormalities. Here, the VGG-16 is used for weight assignment for the classification. Then, using the Mask Region-centric CNN (Mask R-CNN), chromosome defect localization is performed. Experimental results demonstrate that FLEMBODA AI achieves a recall of 95.3%, precision of 94.8%, and an F1-score of 95.0%, outperforming baseline models. Additionally, the U-Net segmentation model attains an accuracy of 93.8%, contributing significantly to improved abnormality localization and classification performance. Overall, the proposed FLEMBODA AI framework provides a reliable as well as effective solution for automated chromosomal abnormality detection, with strong potential for application in clinical diagnostics and future large-scale genetic analysis systems.
Creation of new varieties of tetraploid willow (Salix suchowensis) and their evaluation for salt tolerance.
Deng M, Li M, Qian C … +6 more , Kan S, Mei Y, Wei H, Liu G, Chen Y, Zhang J
Mol Genet Genomics · 2026 Jan · PMID 41559346 · Publisher ↗
To break the germplasm bottleneck that constrains afforestation in coastal and inland saline alkali soils, this study focused on Salix spp., a fast growing, ecological tree genus, and aimed to establish a highly efficien...
To break the germplasm bottleneck that constrains afforestation in coastal and inland saline alkali soils, this study focused on Salix spp., a fast growing, ecological tree genus, and aimed to establish a highly efficient, low chimera protocol for tetraploid willow induction through refined colchicine treatment. The overarching objective was to expand forest genetic diversity and provide both theoretical insights and elite plant materials for the development of salt-tolerant willow cultivars. The colchicine-based chromosome doubling procedure was systematically optimized; 0.1% (w/v) colchicine for 12 h was identified as the optimal condition, and ploidy levels were verified by flow cytometry. Compared with the diploid controls, the induced tetraploids exhibited pronounced gigas characteristics: leaf length and width increased by 1.6- and 1.4-fold, respectively, and leaf fresh weight was 2.4-fold higher. After 14 d of 50 mmol/L NaCl treatment, tetraploids contained only 50% of the K⁺ level observed in diploids, resulting in a significantly higher K⁺/Na⁺ ratio. POD activity in tetraploids was approximately twice that of diploids, and total chlorophyll content was likewise 1.2-fold higher, collectively demonstrating superior growth performance and physiological homeostasis under saline conditions. These results demonstrate that the optimized chromosome doubling protocol markedly improves tetraploid induction efficiency and effectively enhances the salt tolerance of S. suchowensis. Future research will integrate whole genome re-sequencing to dissect dosage effects and identify key genomic loci governing salt tolerance, establish a marker assisted selection framework for accelerated tetraploid breeding, and conduct multi-site field trials to comprehensively evaluate stability and ecological adaptability. Such efforts are expected to expedite the commercial deployment of high salt tolerant willow cultivars in coastal shelter belt construction and large-scale saline alkali land restoration.
Equity-aware variant interpretation needs local allele frequencies and calibrated functional evidence: comment on Bianco & Planello (2025).
Vijayasimha M
Mol Genet Genomics · 2026 Jan · PMID 41559235 · Publisher ↗
Equitable hereditary‑cancer genomics requires variant interpretation that performs reliably in under‑represented and admixed populations-not only in well‑sampled European cohorts. Building on Bianco and Planello (2025),...
Equitable hereditary‑cancer genomics requires variant interpretation that performs reliably in under‑represented and admixed populations-not only in well‑sampled European cohorts. Building on Bianco and Planello (2025), this Comment outlines an equity‑by‑design workflow that couples regional allele‑frequency baselines (e.g., GenomeIndia, IndiGenomes, ABraOM) with calibrated functional evidence from saturation genome editing and related multiplex assays, implemented within updated ClinGen/ACMG‑AMP Bayesian point‑based frameworks. The pipeline defines sub‑national AF strata, quantifies AF uncertainty, maps quantitative functional readouts to PS3/BS3 strengths, and integrates AF, functional, in‑silico and clinical signals with transparent scoring while tracking fairness metrics (e.g., VUS rate ratios) and using patient‑centered reporting language. Overall, routinely combining local population priors with decision‑grade functional likelihoods provides a practical, auditable pathway to reduce VUS disparities and strengthen the global validity of clinical genomic interpretation.
Optimizing computational prediction of shrimp-WSSV protein interactions through integration of homology- and topology-based predictions.
Yang Z, Yuan J, Li S … +2 more , Zhang X, Li F
Mol Genet Genomics · 2026 Jan · PMID 41559231 · Publisher ↗
Understanding and predicting protein-protein interactions (PPIs) between Penaeus vannamei and white spot syndrome virus (WSSV) is essential for elucidating viral infection mechanisms and developing antiviral strategies i...
Understanding and predicting protein-protein interactions (PPIs) between Penaeus vannamei and white spot syndrome virus (WSSV) is essential for elucidating viral infection mechanisms and developing antiviral strategies in shrimp aquaculture. Traditional experimental methods and classical homology-based computational approaches such as STRING have been used to identify shrimp-WSSV PPIs, but both face inherent limitations in accuracy and scalability. Recently, the breakthrough of AlphaFold3 has enabled PPI prediction from the perspective of complex structures, although its performance requires systematic evaluation. To address these gaps, this study establishes an integrated computational framework that combines homology-based network inference and structure-based (topology-based) complex modeling for predicting shrimp-WSSV PPIs. Homology-based interaction networks and 3D structural models of putative PPIs between three WSSV proteins and host proteins were constructed, including 2580 PPIs of wsv067, 389 PPIs of wsv172, and 2310 PPIs of wsv188. Notably, we found substantial discrepancies between STRING- and AlphaFold3-derived predictions, indicating that reliance on a single method may yield an numerous false positives. Nevertheless, interactions with high STRING scores showed a greater likelihood of forming structurally stable complexes in AlphaFold3. By applying dual thresholds (STRING score > 700 and composite AlphaFold3 score > 0.7) and validating representative complexes using molecular dynamics simulations, we identified a small but reliable set of high-confidence PPIs. These host proteins were primarily enriched in DNA replication, highlighting potential targets that may facilitate WSSV replication after invasion. Together, this work establishes a practical framework for prioritizing virus-host PPIs and reveals mechanistically plausible interactions between WSSV and shrimp, offering promising perspectives for antiviral target discovery and health management in aquaculture.
Genomic architecture and transcriptional regulation of cellulose degradation in the novel marine bacterium Pseudoxanthomonas sp. JC1303.
Wang F, Liu Q, Ghonimy A … +2 more , Peng Z, Zhang X
Mol Genet Genomics · 2026 Jan · PMID 41524913 · Publisher ↗
Microbial degradation of cellulose is a fundamental process driving the global carbon cycle and holds immense potential for sustainable biotechnology; however, the genomic mechanisms and transcriptional regulation underl...
Microbial degradation of cellulose is a fundamental process driving the global carbon cycle and holds immense potential for sustainable biotechnology; however, the genomic mechanisms and transcriptional regulation underlying this capability in marine environments remain largely underexplored. To decipher these complex biological strategies, we isolated the novel strain JC1303 from marine sediments and integrated whole-genome sequencing with transcriptomic analysis to systematically characterize its enzymatic arsenal and metabolic adaptations. Whole-genome sequencing revealed that strain JC1303 possesses a circular chromosome of 4.37 Mb in length, with a GC content of 67.41%. Phylogenetic analyses based on the 16 S rRNA gene and whole-genome data suggest that strain JC1303 likely represents a new species within the genus Pseudoxanthomonas. Pan-genome analysis of the genus demonstrates a typical "open" genome architecture with only 3% conserved core genes, highlighting high evolutionary plasticity. In contrast, strain JC1303 has 936 unique genes significantly enriched in metabolism (163 genes) and signal transduction (138 genes), providing a molecular basis for its adaptation to the cellulose degradation niche. Genome mining identified a complete cellulolytic system comprising three endo-β-1,4-glucanases, two cellulase, and four β-1,4-glucosidase, supported by glycolysis/gluconeogenesis, TCA cycle, pentose phosphate pathway, amino acid synthesis pathways, ABC transport systems, and the respiratory chain. Crucially, comparative transcriptomic profiling under cellulose induction validated the functional execution of this genetic potential. Among 1465 differentially expressed genes, the strain exhibited a coordinated strategy: while distinct isozymes were downregulated, a key endoglucanase gene (JC1303_01352) and multiple membrane transporter genes were significantly upregulated. This suggests a specific mechanism coupling extracellular hydrolysis with efficient substrate uptake. In conclusion, this study not only elucidates the genetic blueprint and transcriptional regulation of a new marine cellulolytic species Pseudoxanthomonas JC1303 but also offers theoretical support for engineering robust biocatalysts.
A dynamic RNA editing landscape in porcine spleen highlights a post-transcriptional mechanism for immune maturation.
Zeng L, Li Y, Liu J … +4 more , Liu C, Gao N, He J, Zhang Y
Mol Genet Genomics · 2026 Jan · PMID 41524827 · Publisher ↗
The pig serves as both an important agricultural species and a valuable biomedical model due to its physiological and immunological similarities to humans. RNA editing, especially adenosine-to-inosine (A-to-I) conversion...
The pig serves as both an important agricultural species and a valuable biomedical model due to its physiological and immunological similarities to humans. RNA editing, especially adenosine-to-inosine (A-to-I) conversions, is a key post-transcriptional mechanism that regulates gene expression and immune responses. However, the dynamics of RNA editing during porcine spleen development are still underexplored. To address this, we systematically profiled the RNA editing landscape of Ningxiang pig spleens at three developmental stages (30, 90, and 210 days) to investigate the dynamic regulation of RNA editing during immune system maturation. A total of 72,182 high-confidence RNA editing sites were identified, of which 92.9% corresponded to A-to-I conversions. These sites were predominantly located within swine-specific SINE retrotransposons (PRE-1/Pre0_SS). Across developmental stages, 2,649 sites exhibited significant differential editing, indicating that RNA editing activity is dynami-cally regulated during spleen development. Functional enrichment analysis of the differentially edited genes revealed enrichment in immune-related pathways, particularly those involved in T cell activation, cytokine signaling, and antiviral defense. Protein-protein interaction analysis further revealed two key RNA-editing-associated modules centered on PTPN11 and EP300, underscoring regulatory of immune signaling and disease response. Collectively, these results demonstrate that RNA editing constitutes a dynamic and developmentally regulated post-transcriptional layer during spleen development. Our findings highlight RNA editing as an important regulatory mechanism contributing to immune maturation and provide a valuable resource for future studies on immune regulation and disease resistance in pigs.
ZMYM3 S464: a potential phospho-regulatory hub in epigenetic remodeling and oncogenesis.
Pai A, Mahin A, Ummar S … +4 more , Gopalakrishnan AP, Shivamurthy PB, Rajeev AC, Raju R
Mol Genet Genomics · 2026 Jan · PMID 41493627 · Publisher ↗
Dysregulated epigenetic control and DNA-repair defects are hallmarks of many cancers and neurodevelopmental disorders. ZMYM3, a chromatin-associated zinc-finger protein, orchestrates histone deacetylation, BRCA1-dependen...
Dysregulated epigenetic control and DNA-repair defects are hallmarks of many cancers and neurodevelopmental disorders. ZMYM3, a chromatin-associated zinc-finger protein, orchestrates histone deacetylation, BRCA1-dependent homologous recombination (HR), and cytoskeletal organisation, yet the post-translational mechanisms that govern its activity remain largely unknown. Here we integrate global phosphoproteomics data to define the regulatory landscape of ZMYM3, with a focus on the highly recurrent phosphosite S464 located in its zinc-finger domain. S464 is detected in > 50% of curated human-cell-line datasets and is co-regulated with four upstream kinases (CDK13, HIPK1, CDK9, CLK3) and 15 binary interactors including BRCA1, HDAC6, and SWI/SNF components. Positively co-phosphorylated networks are enriched for chromatin remodelling, mitotic segregation, DNA-damage response, and cytoskeletal dynamics. cProSite analysis of patient tumours reveals striking S464 hyper-phosphorylation in breast and ovarian cancers, correlating with HR-deficiency signatures. ZMYM3 S464 emerges as a phospho-regulatory hub that coordinates epigenetic silencing, HR repair, and mitotic fidelity. Its cancer-type-specific upregulation offers a novel biomarker for HR-deficiency stratification and a therapeutic entry point for modulating BRCA1 function or epigenetic drug sensitivity; functional validation in HR-deficient models is now warranted.
Comparative and functional genomics of yeast Pichia kudriavzevii RWT identify potential genes involved in aflatoxin B1 detoxification.
Astuti RI, Maulana I, Maryam R
Mol Genet Genomics · 2026 Jan · PMID 41493614 · Publisher ↗
Aflatoxin B1 (AFB1) is a potent mycotoxin that threatens food safety and human health. This study investigated the capacity of yeast isolates to tolerate and detoxify AFB1 and performed genomic characterization of the mo...
Aflatoxin B1 (AFB1) is a potent mycotoxin that threatens food safety and human health. This study investigated the capacity of yeast isolates to tolerate and detoxify AFB1 and performed genomic characterization of the most active strain. Among several Pichia and Wickerhamomyces isolates, Pichia kudriavzevii RWT exhibited the strongest tolerance, maintaining growth at AFB1 concentrations up to 200 ppb and decontaminating 26.5% of AFB1 within six hours, more than twice the reduction achieved by the next best isolate. In contrast, heat-killed yeast cells showed no significant reduction activity. This suggests that cell wall adsorption alone is insufficient for meaningful AFB1 reduction in this strain and highlights the importance of enzymatic or transporter-mediated mechanisms that require live, metabolically active cells. Whole-genome sequencing of RWT yielded a 10.86 Mb assembly with 5,445 predicted proteins grouped into 4,274 orthologous clusters, sharing 2,448 core clusters with related yeasts but retaining 953 clusters unique to Pichia species. Functional annotation highlighted genes potentially involved in AFB1 detoxification, including predicted cytochrome P450, epoxide hydrolase (LAP2), glutathione-S-transferase (URE2), and the ABC transporter (YCF1), suggesting pathways for AFB1 activation, glutathione conjugation, and vacuolar sequestration. AFB1 treatments were found to increase the gene expression of those key genes involved in AFB1 detoxification. Comparative genomics confirmed that RWT's genome size and core gene content are typical of P. kudriavzevii, while its unique clusters are enriched in membrane transport, stress response, and metal-ion binding functions. These findings position P. kudriavzevii RWT as a promising candidate for biological AFB1 mitigation, providing a genetic basis for its robust detoxification capacity.
Examining sleep signals at the cradle of life: can phylogenomic analysis of the Last Universal Common Ancestor (LUCA) reveal the fundamental role of sleep?
Pandi-Perumal SR, Saravanan KM, Spence DW … +3 more , Paul S, Namasivayam GP, Chidambaram SB
Mol Genet Genomics · 2026 Jan · PMID 41493494 · Publisher ↗
Sleep is a ubiquitous phenomenon throughout the animal kingdom; nonetheless, its evolutionary origins remain mostly enigmatic. Comprehending the origins of the biological systems governing sleep necessitates methodologie...
Sleep is a ubiquitous phenomenon throughout the animal kingdom; nonetheless, its evolutionary origins remain mostly enigmatic. Comprehending the origins of the biological systems governing sleep necessitates methodologies that extend beyond comparisons of current animals and instead investigate the profound history of their molecular underpinnings. This study used a molecular paleobiology framework toexamine the evolutionary origins of sleep-related genes by mapping their homologs onto the reconstructed genome of the Last Universal Common Ancestor (LUCA). Utilizing phylogenomic reconstruction and functional enrichment studies, we ascertain that multiple gene families crucial for human sleep, especially those governing circadian timing, fundamental metabolism, and cellular signaling, were extant in this ancient progenitor. The results substantiate the perspective that the chemical elements facilitating sleep did not arise as new innovations but rather evolved from ancient cellular systems that initially served fundamental physiological roles. Our research demonstrates a profound evolutionary pathway in which the intricacy of sleep developed through the incremental co-option and amalgamation of conserved genomic modules. This study presents a novel viewpoint on the emergence of essential physiological activities from primordial and universal biological mechanisms.
A systematic review of genetic association studies on the susceptibility of preterm birth in Asia.
Mohamed Ibrahim NH, Aissvarya S, Nordin N … +4 more , Hamid HA, Thilakavathy K, Mohd Jamil AA, Zainudin Z
Mol Genet Genomics · 2025 Dec · PMID 41467952 · Publisher ↗
Preterm birth (PTB) is a leading cause of prenatal and infant mortality and morbidity, yet its molecular mechanisms remain poorly understood. This systematic review aims to enhance understanding of PTB's molecular geneti...
Preterm birth (PTB) is a leading cause of prenatal and infant mortality and morbidity, yet its molecular mechanisms remain poorly understood. This systematic review aims to enhance understanding of PTB's molecular genetics and to identify potential biomarkers and therapeutic targets by comprehensively analyzing genetic association studies conducted among Asian populations. A systematic search was performed across six online databases, including Google Scholar, Science Direct, Clinical Trials, PubMed, Cochrane, and MyCite, using a combined search strategy of PTB, gene polymorphisms, and Asia (PROSPERO protocol: CRD42023458957). Peer-reviewed articles focusing on the effects of genetic association on labor progression in the Asian population were included. Subsequently, data extraction encompassing study design, demographics, genetic determinants, and effect estimates were collected. Quality assessment was conducted for each study using the Quality of Genetic Association Studies (Q-Genie) tool. Due to heterogeneity among study designs, genetic variants, and reported outcomes, a meta-analysis was not performed; instead, a systematic narrative synthesis was conducted. Out of 2,412 screened articles, 16 met the inclusion criteria and passed the Q-Genie quality assessment. These studies collectively investigated 37 polymorphisms within 25 genes across various Asian ethnic groups. These genes exhibited associations with various aspects of PTB, shedding light on the roles of innate immune responses, inflammation, myometrial quiescence, oxidative stress, and uteroplacental blood flow in PTB pathogenesis. This review highlights the role of genetics role in PTB susceptibility across Asian populations and the need to explore candidate genes and their interactions to uncover the underlying molecular mechanisms.
Unveiling the molecular landscape of differentially expressed genes in obesity.
Pujari SN, Hoskeri HJ
Mol Genet Genomics · 2025 Dec · PMID 41460343 · Publisher ↗
Lipid-associated disorders such as obesity are major global health challenges, primarily driven by dysregulated lipid metabolism and associated alterations in gene expression and protein interactions. Understanding these...
Lipid-associated disorders such as obesity are major global health challenges, primarily driven by dysregulated lipid metabolism and associated alterations in gene expression and protein interactions. Understanding these molecular mechanisms is essential for identifying new therapeutic targets. This study investigates the molecular landscape of lipid dysregulation through differential gene expression analysis in hyperlipidemic rat models. By integrating multiple datasets and computational tools, we aimed to identify key proteins involved in obesity pathogenesis, thereby contributing to the development of targeted therapeutic strategies for lipid-associated disorders. A comprehensive search was conducted to identify differentially expressed genes associated with lipid disorders by analyzing metadata from various public databases, leading to the curation of four distinct datasets. Gene Ontology (GO) analysis was performed using the G: Profiler server, and protein-protein interaction (PPI) networks were constructed using Cytoscape. Cluster analysis with MCODE identified densely connected subnetworks, while pathway enrichment analysis using KEGG-KASS explored gene involvement in biological pathways. GO analysis revealed critical pathways involved in lipid metabolism, particularly those related to lipid oxidation and homeostasis. Pathway enrichment analysis identified three pivotal genes-Akt1, Nr1h3, and Il6-with Nr1h3 emerging as a prominent target under treatment conditions. Il6 showed significance in both disease and treatment contexts, suggesting its potential as a therapeutic target. These genes were also linked to obesity, fatty liver disease, and atherosclerosis in rat datasets, with supporting evidence from previously published rodent and human studies.
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