Stiphodon is a genus of gobioid fishes found primarily in freshwater streams on islands throughout the Indo-Pacific region. It is the most speciose genus of Sicydiinae, with more than three dozen named species. Complete mitochondrial genome (mtDNA) sequences were determined for three species, namely Stapledon atropurpureus, Stapledon elegans, and Stapledon semoni. Maximum likelihood and Bayes inference inferences from 13 protein-coding genes (11,433 bp) or the COXI gene (1,551 bp) alone were made on these three together with four mitogenomes previously available. S. percnopterygionus and S. tuivi formed an outgroup to the other five Stiphodon species, meanwhile Stapledon atropurpureus and S. semoni were recovered as sister species. The ratios of the non-synonymous to the synonymous substitution rates for all PCGs were in the range 0 < (Ka/Ks) < 1, which suggests they have been subject to purifying selection.
Nonalcoholic fatty liver disease (NAFLD) is a complex condition influenced by metabolic and genetic factors, yet the shared genetic architecture underlying its progression remains poorly understood. The aim of this study was to employ genomic structural equation modeling (GSEM) to elucidate the genetic architecture linking NAFLD with key metabolic traits-including insulin resistance, body mass index (BMI), hemoglobin A1c (HbA1c), and liver fibrosis using summary statistics from large-scale genome-wide association studies. By harmonizing 2.18 million variants across five genome-wide association studies (GWAS) datasets, we identified 134 genome-wide significant loci that mapped to 24 genes. GSEM revealed a latent genetic structure composed of two distinct dimensions: a metabolic regulation factor primarily driven by insulin resistance, BMI, and HbA1c; and a structural pathology factor specifically associated with liver fibrosis. These factors explained 65.5 r_g=0.07 ), indicating their genetic distinctness. Additionally, integrating Mendelian randomization with liver transcriptome profiling, we characterized how the 24 genes contribute to disease and identified mitochondrial glycerol-3-phosphate acyltransferase (GPAM) as the key gene that causally links lipid metabolism to fibrogenesis. In conclusion, we present the first genetically grounded mechanism for the progression of NAFLD to fibrosis. This mechanism encompasssses genetic variants, dysregulated gene expression, metabolic disturbances, and the processes involved in fibrotic remodeling. This research establishes a genetic framework for understanding the pathogenesis of NAFLD and highlights novel therapeutic targets for intervention.
The EDAR gene is a classic target of positive selection in humans, mainly through the nonsynonymous variant rs3827760 (EDARV370A) associated with ectodermal traits. Using high-resolution data from the 1000 Genomes Project, we combined sliding-window F_ST, BayeScan, and extended haplotype homozygosity (EHH) analyses to examine global and Latin American patterns of differentiation. Globally, a strong signal of positive selection was confirmed at EDAR, dominated by the rs3827760 haplotype background and its extended linkage disequilibrium structure. In contrast, within Latin America, differentiation reflected admixture-driven haplotype persistence rather than contemporary selection. A genome-wide FST scan comparing individuals from the upper and lower quartiles of Native American ancestry showed that EDAR lies among the most highly differentiated regions in this contrast, consistent with ancestry-driven haplotype structure rather than post-admixture adaptive evolution. These results indicate that EDAR retains its evolutionary signature globally but not within recently admixed populations, where demographic history rather than selection shapes its genetic landscape.
This article has been retracted by the Editor-in-Chief following concerns raised after publication. Specifically, duplication of two lanes within the same blot was identified in Figure 1b, where different samples were represented using the same data. The authors were unable to provide a satisfactory explanation or a suitable replacement figure. As a result, the editor has lost confidence in the data and conclusions presented in the study. One author (Swarup Roy Choudhury) disagreed with the retraction. The remaining authors did not respond to correspondence from the publisher regarding this issue.
We present a COI-based assessment of freshwater leeches in Azerbaijan’s Lankaran–Astara region. Between 2019 and 2021, we sampled 136 individuals from 33 wetlands across six districts and generated 15 new COI sequences, which were combined with curated GenBank records. Four species were confirmed in three families: Dina lineata (Erpobdellidae), Helobdella stagnalis (Glossiphoniidae), Hirudo orientalis (Hirudinidae), and Trocheta sp. (Erpobdellidae). Azerbaijani D. lineata populations occur as two distinct clades, one that includes an individual from Iraq (Lineage A) and one that includes an individual from Iran (Lineage B). These Asian lineages are separated from European D. lineata. An Azerbaijani Trocheta sp. specimen (FSM20) clusters with one from Iran on a distinct branch that is > 8
Pathogenic variations in DNA checkpoint kinases, cell cycle regulation, and DNA-damage repair genes are responsible for hereditary cancer predisposition. In a woman with a history of multiple primary cancers (carcinoma rectum and papillary carcinoma of thyroid) at a young age, whole exome sequencing (WES) of the blood revealed a likely pathogenic germline variation NM_001161346.2(CHFR):c.1231C[T (ClinVar variation ID: 1802254) in the CHFR gene. The CHFR gene encodes an E3-ubiquitin ligase and is required for antephase checkpoint maintenance and cell cycle entry into mitosis. It has previously been shown to be silenced in many human tumour types, including colon, lung, and esophageal tumours. Herein, we describe what is possibly the first case of CHFR-related hereditary cancer predisposition syndrome and, using RNA sequencing, elucidated the pathways associated with CHFR inactivation.
RASopathies are a group of developmental disorders caused by variations in genes of the RAS/mitogen activated protein kinase (MAPK) pathway and affect 1 in 1000 individuals worldwide. Due to overlapping clinical features, accurate diagnosis is challenging and therefore we used next-generation sequencing (NGS) panels as an effective molecular diagnostic tool. Targeted sequencing was performed on 130 samples using a multigene panel comprising of 21 RASopathy genes. Molecular analysis revealed variations in 74 individuals (57%). Pathogenic or likely pathogenic variations were observed in 60/74 (81%) of the cases, 13 (17.5%) had variant(s) of uncertain significance (VUS), and one novel variant was identified in RASA2 whose pathogenicity has not yet been established. In individuals with Noonan Syndrome, pathogenic variants were identified in eight different genes mainly PTPN11, SOS1, RAF1 and LZTR1. Nine clinically diagnosed Cardio-facio-cutaneous syndrome cases harboured variations in BRAF, MAP2K2 and MAP2K1 The c.34G>A variant in HRAS was seen in all nine individuals diagnosed with Costello syndrome. This study provides a comprehensive molecular and clinical profile of the largest Indian RASopathy cohort. The use of targeted gene panel has increased the variation detection rate in affected individuals.
Somatic mutations gradually accumulate as an organism develops and grows. These somatic mutations are not only associated with disease but also serve as important indicators: at the cellular level, they reveal the internal and external effects cells have undergone; at the organism level, they can reveal species-specific patterns. In this study, we conducted whole-genome sequencing on single-cell clonal expansion samples from various tissues of mice, pigs, and human cadavers. A total of 69 samples were analyzed, including muscle, skin, kidney, and other tissues. We compared the number of single nucleotide variants and structural variants across species and tissues, observing differences in the distribution and characteristics of these mutations between humans, mice, and pigs. Additionally, we performed mutational signature analysis to explore the genomic landscapes of these organisms. UV radiation-related mutational signatures were identified in human skin but not in muscle or other animal samples. Furthermore, two mutational signatures, catalogue of somatic mutations in cancer (COSMIC) single base substitution 5 and 40, were mostly present in mice and pigs, although their relative contributions differed. Through these results, we present several hypotheses for estimating species and tissue similarity using Ti/Tv (transition/transversion) ratio, diversity in the number of mutations in the same tissue origin, and the number of single-nucleotide variants is not proportional to that of structural variations. These comparative analyses of genomic alterations across species enhance our understanding of the mechanisms driving somatic mutation accumulation, offering valuable insights into the shared patterns of genomic alterations across species and their implication for animal disease models.
Craniometaphyseal dysplasia (CMD) is characterized by metaphyseal dysplasia, sclerosis of the skull base, and craniofacial bone overgrowth. The autosomal dominant form of CMD (OMIM: 123000) is associated with features such as mandibular prognathism, dental misalignment, and bony paranasal bossing. In contrast, the autosomal recessive form (OMIM: 218400) can result in severe distortion of the craniofacial structure, accompanied by complications such as cranial nerve compression, facial palsy, deafness, and visual impairment. Mutations causing CMD have been linked to the ANKH gene sequence variants. This case report describes a 11-year-old male diagnosed with CMD based on clinical and genetic findings. The patient presented with facial asymmetry, mandibular prognathism, delayed intellectual response, and gradual visual impairment, culminating in optic nerve compression and partial blindness. Radiographic evaluation revealed mixed dentition, thickened skull bones, cranial suture fusion, and Chiari I malformation. Biochemical analysis indicated hyperdense bone with normal serum calcium and phosphorus levels. Genetic testing confirmed an autosomal dominant pathogenic variant of a heterozygous nonframeshift deletion mutation of the ANKH gene (c.1124_1126del, p.Ser375del).
The American brackish water mussel, Mytella strigata (Hanley, 1843), is an invasive species with a growing global footprint, recently recorded in the Indian coastal ecosystems. Despite its rapid spread and potential ecological impact, no genetic data are available for Indian populations. We assessed the genetic diversity and population structure of M. strigata with a 683 bp fragment of the mitochondrial cytochrome b (cyt b) gene from 71 individuals collected from six locations along the Arabian Sea and the Bay of Bengal. Sixteen haplotypes were identified. The Vembanad lake and Ennore creek populations on the Kerala/West Coast and Tamil Nadu/East Coast, respectively, had the highest haplotype and nucleotide diversity, whereas other West and East Coast populations had very low diversity. AMOVA indicated that 16.7% of the genetic variance occurs among populations, which contrasts with the expectation for a species with a high dispersal of planktonic larvae. The haplotype network includes both shared and population-specific haplotypes, consistent with multiple introduction events and restricted gene flow rather than range expansion from a single source. Neutrality and mismatch analyses showed no significant evidence of demographic expansion, which likely reflects the limited resolution of the short cyt b fragment. The invasion history of M. strigata in India is complex, and is characterized by independent introductions, local diversification, and constrained post-settlement dispersal.
Nitrogen is a primary factor affecting the yield and quality of tobacco. Insufficient nitrogen results in poor tobacco output and poor leaf quality; in contrast, excessive nitrate can lead to delayed maturity and poor quality of cured tobacco leaves. To elucidate the molecular mechanism underlying the response of tobacco to low nitrogen, we conducted a multiomics analysis of tobacco plants treated with normal (7.5 mM) or low nitrogen (0.75 mM). Our results revealed that after 15 days of low-nitrate treatment, the plants exhibited stunted growth, yellowed leaves, and significant growth inhibition. The total nitrogen levels, and the activities of glutamine synthetase and nitrate reductase in the leaves also decreased significantly. Transcriptome analysis of the tobacco plants under low-nitrogen stress revealed 896 differentially expressed genes, with 404 genes upregulated and 492 genes downregulated in comparison with those in the control. Among the upregulated genes, the expression of Nitab4.5_0000970g0150, which is involved in galactose metabolism, significantly increased. Subsequent metabolome analysis revealed that 28 metabolites significantly changed under low-nitrogen treatment, including 23 metabolites whose levels increased and 6 whose levels decreased compared with those in the control. The increased metabolites were also enriched in galactose metabolism. Integrated transcriptome and metabolome analyses revealed that three pathways significantly changed—amino acid synthesis and metabolism, galactose metabolism and trehalose-6-phosphate metabolism—among which galactose metabolism is important for tobacco in response to low nitrogen stress. These findings provide a theoretical basis for further research on the function of nitrogen regulatory genes in tobacco and for the breeding of tobacco varieties with high nitrogen use efficiency.
Scanning genomes for selection signals could illuminate the impact of domestication, natural, and artificial selection on the phenotypic traits of cattle breeds. The present study investigated the diverse genomic selection signatures using whole genome sequencing data from 15 pooled samples of five indigenous cattle breeds of Tamil Nadu: Alambadi, Bargur, Kangayam, Pulikulam, and Umblachery. Two approaches, namely composite likelihood ratio (CLR) and fixation index (FST), were employed to detect selection signatures from the 1,390,449 filtered single-nucleotide polymorphisms. The analysis identified 7250 and 806 genomic regions containing selective sweeps in 1238 and 101 candidate genes using CLR and FST methods, respectively. These regions were predominantly associated with production traits (PAIPI, NNT and OCIAD1), coat colour (MC1R, KIT, KDR and PDGFRA), disease resistance (TCF25, CDH15 and SPIRE2), and adaptation to tropical climates (SLC22A31 and SPG7). Particularly, six regions were shared across all the five cattle breeds, of which, five were intergenic regions and one had a candidate gene, GALNTL6, associated with susceptibility to bovine tuberculosis. A total of 12 candidate genes were common between CLR and FST methods, relating to production, disease resistance, and behavioural traits. NETWORK analysis revealed six candidate genes allied with calving ease (JAK1 and DOCK1), milk fat yield (ITGA1), bovine respiratory disease susceptibility (ITGA3 and ITGAL), and meat and carcass traits (EPS15L1). This study presents the first genomewide map of selective sweeps in Tamil Nadu cattle breeds, providing insights into selection signatures and candidate genes that could enhance genome-assisted breeding for improved production and health.
Eukaryotic proteomes harbour tandem repeats (TRs) of amino acids that may play critical roles in the biology of organisms. While a few TRs have been shown to contribute to protein structure and function, information about the vast majority of repeat regions remains obscure. This article reports a detailed computational analysis of the repeat content of different Plasmodium species proteomes, identifying P. falciparum (Pf) and P. vivax to be exceptionally rich in TR regions. P. falciparum ‘repetome’ was found to carry longer TRs, which were majorly present in exported parasite proteins, important for pathogen survival and immune evasion. Short and intermediate TRs of P. falciparum showed a bias towards Asparagine usage, suggesting an evolutionary outcome influenced by replication slippage and positive selection. Gene ontology analysis revealed the largest proportion of TR containing Pf proteins to be involved in binding nucleic acids, proteins and other small molecules. Surprisingly, the Plasmodium specific variable surface antigen (VSA) families known to have roles in immune evasion and cytoadherence were found to contain low repeat content. Our analysis also revealed that all the TR containing VSAs were sero-reactive, where several antigenic peptides were present within the repeats. Three-dimensional structure predictions of TR regions showed several repeats to form ordered super-secondary conformations, which are often reported to facilitate intermolecular interactions. Overall, this comprehensive study provides glimpses into the probable roles of TRs in Plasmodium biology and also suggests a novel method for understanding protein function via characterization of repetitive sequences.
Hippophae rhamnoides ssp. turkestanica, a subdioecious plant inhabiting the cold desert of the Indian Himalaya, has gained immense recognition for its nutritional and medicinal values. In recent years, the plant species has proven to be a suitable system to understand the evolution of dioecy. Despite its biological significance, the cytogenetics of this dioecious plant is unclear due to various conflicting accounts of its X-Y chromosome system, particularly the length of Y-chromosome. In this study, we resolved these ambiguities through comprehensive cytogenetic analyses across diverse western Himalayan populations. Using morphometric analysis and fluorescence in situ hybridization (FISH) with a gender-specific marker (HRMSSR), we confirmed homomorphic XX chromosomes in females and heteromorphic sex-chromosomes in males with a notably smaller Y-chromosome. The investigation also revealed a predominant somatic chromosome number of 2n = 24, although minor deviations (2n = 18, 20, 22) appeared at the seed level. These findings highlight an evolutionarily advanced sex-chromosome system. This first detailed cytogenetic investigation of Himalayan Seabuckthorn provides critical insights into the chromosomal architecture, laying a crucial foundation for future evolutionary, genomic, and conservation studies in the species.
Red tilapia has gained increasing popularity worldwide in the commercial aquaculture production due to its rapid growth and delightful taste. However, the occurrence of skin colour variation poses a significant challenge to the advancement of commercial culture. Furthermore, the molecular regulatory mechanism and genetic basis for the distinct skin colouration in red tilapia remain undisclosed. In this study, a comprehensive transcriptome analysis was conducted on red tilapia with different skin colour by integrating PacBio Iso-seq technology with Illumina short-read sequencing methods. A total of 41.38 Gb of clean data was generated, resulting in the acquisition of 30,970 transcripts. Among them, 10,829 transcripts were successfully annotated in at least one public database. In addition, 10,827 coding sequences, 452 transcription factors, and 781 lncRNAs were identified in new transcripts. Furthermore, we performed RNA-seq analysis to identify skin colour-associated genes in red tilapia with three colour spots (white spots, W; black spots, B; red spots, R). The results revealed the identification of 278 differentially expressed genes (DEGs) between the comparison groups, which included B vs R, B vs W, and W vs R. Among them, some known genes were found to be involved in regulating the skin pigment synthesis, including PMEL, Wnt-4, melanoregulin and ALK in red tilapia with different skin colour. In addition, some pathways, including melanogenesis (ko04916), ECM-receptor interaction (ko04512), Hedgehog signaling pathway (ko04340) and steroid hormone biosynthesis (ko00140), were associated with the skin pigment synthesis in red tilapia. Furthermore, the quantitative real-time PCR analysis confirmed a moderate correlation (coefficient of 0.68) between the results obtained from the qPCR and RNA-seq methodologies. In summary, our findings will significantly contribute to the enhanced comprehension of the molecular regulatory mechanisms underlying the variation in skin colour observed in red tilapia.
Ganoderic acid DM (GA-DM), a triterpenoid derived from Ganoderma lucidum, exhibits anti-cancer and anti-diabetic activities, but the underlying mechanisms of action remain unclear. To identify genetic modulators of the GA-DM response, we conducted a genome-wide CRISPR/Cas9 knockout screen in human melanoma cells. The screen revealed key roles for genes regulating lipid metabolism and inflammatory signalling, particularly those involved in the SREBP (sterol regulatory element-binding protein) and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathways, in the cellular response to GA-DM. While loss of genes involved in the regulation of cholesterol biosynthesis conferred resistance to GA-DM, disruption of genes involved in ubiquitin-mediated proteolysis and the Hippo pathway sensitised cells to GA-DM. Inflammatory genes enriched at later time points suggests that a delayed cellular response contributes to cytotoxicity. Our findings propose a mechanistic model wherein GA-DM perturbs lipid and inflammatory pathways to exert cytotoxic effects and highlight potential targets to enhance its therapeutic efficacy. This work demonstrates the utility of functional genomics in elucidating the mechanisms of action of natural products and guiding rational drug development.
Dps and MSUD: Twenty-five years ago, Robert Metzenberg and colleagues discovered why a cross between a normal euploid Neurospora crassa strain and one carrying any chromosome segment duplication (N X Dp) was barren and produced only a few exceptional progeny ascospores. The culprit was a novel gene-silencing process, which they named meiotic silencing by unpaired DNA (MSUD; Cell 107, 905-916, 2001).
The father of sociobiology, Edward Wilson, described him as 'the most unpleasant human being I had ever met'. He was the first living laureate to auction his Nobel Prize. He said that because of some of his views and beliefs, he had become an 'unperson'. 'No one really wants to admit I exist.' 'Because I was an ''unperson'', I was fired from the boards of companies, so I have no income, apart from my academic income.' The 'unperson' is James Dewey Watson. He won the Nobel Prize at the age of 34, for the work he published in 1953, when he was only 25. The 1953 article in Nature, co-authored with Francis Crick, concluded with the famous understatement: 'It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.' Watson died on 6 November 2025 at the age of 97.
Schimke immunoosseous dysplasia (SIOD) is an uncommon inherited genetic disorder resulting from pathogenic variants in the SMARCAL1 gene. This complex condition exhibits a wide range of clinical features, including skeletal abnormalities, steroid-resistant nephrotic syndrome, and immune system deficiencies. In this study, we report a case series of three patients diagnosed with SIOD, each harbouring copy number variants in the SMARCAL1 gene. The cases expand the current understanding of the genetic diversity underlying SIOD and highlight the significance of copy number variations as a pathogenic mechanism. Our findings contribute to broadening the genotypic spectrum associated with SIOD and underscore the importance of comprehensive genetic analysis for accurate diagnosis and management of this rare disorder.
The ornamental fish Amatitlania nigrofasciata, known as the convict or zebra cichlid, is a small Central American tropical freshwater fish that also serves as a model for behavioural studies. Its phylogenetic relationship with other cichlids in the tribe Heroini remains unclear. Here, we sequenced the mitogenome of A. nigrofasciata. The mitogenome spans 16,529 bp and includes the standard complement of 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and one D-loop region, with the same order and strand distribution as those of other cichlids. Phylogenetic analysis of the 13 PCGs showed that A. nigrofasciata is more closely related to Amphilophus, in a clade including Parachromis, Petenia, and Cryptoheros, with this clade forming a core group of amphilophines within the cichlid tribe Heroini.
