Genomics最新文献

Formerly considered as part of "junk DNA", pseudogenes are nowadays known for their role in the post-transcriptional regulation of functional genes. Their identification also contributes to a better understanding of gene evolution, particularly in relation to adaptive responses and the evolution of multigene families. Despite this, there is, to our knowledge, no fully automatic pipeline allowing annotation of the pseudogenes on a whole genome. Here, we propose a new software named Pseudo-Gene Retriever (P-GRe). This is a completely automated pseudogene prediction tool requiring only a genome sequence, its corresponding GFF annotation file, and a protein sequences file. The aligner miniprot has been integrated in our pipeline, because of its high speed and sensitivity. With several filtering and post-analysis steps P-GRe outperforms existing software, while being more sensitive and bringing the new capacity of annotating unitary pseudogenes.

Skeletal muscle development is a complex biological process orchestrated by precisely regulated gene expression networks. Understanding the molecular mechanisms during fetal myogenesis is crucial for improving meat yield and quality in livestock. In this study, we performed RNA-seq analysis on skeletal muscle tissues from Chinese Merino sheep across 11 key developmental time points, from embryonic day 26 (D26) to near birth (D135). Using weighted gene co-expression network analysis (WGCNA), we identified nine distinct gene modules significantly associated with specific developmental stages. These modules revealed stage-specific biological processes, including myogenic progenitor cell (MPC) proliferation and differentiation, primary (PM) and secondary myofiber (SM) formation, energy metabolism, and muscle maturation. Key hub genes and signaling pathways-such as Wnt, TGF-β, MAPK, and PI3K-AKT-were further validated through functional enrichment and protein-protein interaction (PPI) networks. Notably, we identified critical developmental transition points at D29 (MPC differentiation initiation), D45 (embryonic-to-fetal transition), and D85 (myofiber maturation shift). Moreover, several novel hub genes, including CORIN, SMOC1/2, and ADAMTS family members, were identified. In summary, by identifying nine stage-specific co-expression modules, pinpointing three pivotal developmental transitions (D29, D45, D85), and uncovering novel hub genes of potential regulatory importance, this study provides a systems-level framework for understanding ovine fetal myogenesis and offers candidate targets for livestock genetic improvement.

The Small-Tailed Han (STH) sheep milk has significantly higher fat and protein than DairyMeade (DM) sheep milk. Further study found that the expression of whey protein secretoglobin family 2 A member 2 (SCGB2A2) in STH sheep milk was significantly higher than in DM sheep milk. Thus we surmise that the SCGB2A2 may be involved in the regulation of the mammary biological function. Here, the expression of SCGB2A2 at different lactation periods was detected first. Then the cell proliferation and milk component synthesis effects on ovine mammary epithelial cells (OMECs) were analyzed. And the CUT&Tag analysis was used to identify SCGB2A2 target binding sites at the genome. The transcriptome of SCGB2A2 overexpression and knockdown OMECs was analyzed. Two co-analyses were conducted to further screen out SCGB2A2 potential target genes. Finally, the potential interacting protein was verified by CO-IP and UHLP-MS analysis. Results showed that the SCGB2A2 was expressed highest at the colostrum stage and lowest at the dry milk stage. Immunohistochemical analysis showed that it was mainly expressed in mammary epithelial cells. CCK8 and cell cycle analysis showed that SCGB2A2 promotes the OMECs proliferation. Milk components synthesis detection found that the SCGB2A2 was positively correlated with the CSN2, lactose, and triglyceride (TG). CUT&Tag and transcriptome co-analyses found that 20 genes were consistently detected, including FBP2, IFIT3 and so on. CO-IP analysis demonstrated that mTOR interacted with SCGB2A2. Taken together, we demonstrated that SCGB2A2 plays a positive role in OMECs proliferation and biosynthesis of milk components. Some SCGB2A2 direct regulated genes are involved in the cell proliferation. The regulation of SCGB2A2 for milk components biosynthesis mainly interacts with mTOR. However, the specific regulatory mechanism is needed to further study.

The Jinhua (JH) pig is a renowned Chinese indigenous breed distinguished by their two-end black phenotype, serve as the exclusive genetic resource for producing Jinhua ham. However, there is currently limited knowledge about the genetic structure and characteristics of JH pigs. This study employed whole-genome sequencing of 1238 individuals representing 67 breeds/lines to elucidate the genetic architecture of JH pigs. Population structure analysis revealed five distinct geographic clusters within Chinese indigenous pigs (North China/CCN, Central China/CCN, East China/ECN, South China/SCN, Southwest China/SWCN), with JH forming an early-diverging lineage in the ECN group exhibiting unique ancestry patterns. Genome-wide scans identified 7995 signatures of positive selection (iSAFE; FDR < 0.05). These signals were enriched in pathways related to immunity, neurodevelopment, and lipid metabolism. Key candidate genes (CLEC7A, D2HGDH, NOVA1) demonstrated breed-specific expression. Balancing selection analysis detected 4630 signals converging on PLA2G2A, a metabolic hub gene influencing intramuscular fat deposition. Two haplotypes (Hap1:41%; Hap2:59%) exhibited antagonistic pleiotropy: Hap1 was associated with enhanced growth performance, whereas Hap2 correlated with superior carcass quality. Our integrative analysis demonstrates that germplasm traits of JH pigs, including tender marbling, disease resilience, and roughage utilization efficiency, result from synergistic effects of directional selection on metabolic/immune genes and balancing selection maintaining fitness trade-offs. This study establishes a framework for delineating adaptive mechanisms in indigenous livestock, providing critical insights for genomic conservation and precision breeding.

The alpaca (Vicugna pacos) genome poses assembly challenges due to pervasive complex repetitive sequences accounting for approximately 16% of the genome resulting in assembly errors, gaps, and collapsed sequences that have impacted both the quality and completeness of previous alpaca genomes. Here we used PacBio HiFi long reads, Hi-C chromatin conformation capture, optical genome mapping, and manual curation to construct VicPac4, a 2.6Gb alpaca genome of which 2.1Gb is assembled into 36 alpaca autosomes and the X chromosome, each represented by a single scaffold. While all chromosomes improved in size and contiguity, the X chromosome showed the greatest improvement and allowed demarcation of the 6.2 Mb pseudoautosomal region. VicPac4 incorporates several previously unresolved repetitive regions, such as telomeres in 30 chromosomes, nucleolus organizer regions (NORs) in two chromosomes, and 15 tentative centromeres. Notably, we identified a novel tandemly repeated satellite (SAT) exclusive to South American camelids (SAC). The SAC-SAT, with a 267 bp repeat motif, constitutes 2.42% of the alpaca genome and colocalizes with NORs in all SAC species. As most NORs remained unassigned, their numbers and chromosomal locations in camelids were studied by FISH and Oligo-FISH, revealing extensive dynamism across chromosomes, individuals and species. Resolution of NOR positional variation is essential to the understanding of rDNA-associated disease such as minute chromosome syndrome, which induces infertility in female alpacas. Until the development of telomere-to-telomere resources, VicPac4 stands as the most complete and accurate reference among South American camelids, offering a powerful resource to capture genetic variation in the species and advance genomics of alpaca biology and populations.

Background & aims: The interaction between systemic lupus erythematosus (SLE), excess body weight, and epigenetic variation remains poorly understood. This study investigated the association between excess body weight and genome-wide DNA methylation profiles in subcutaneous adipose tissue (SAT) from patients with SLE.

Methods: In this cross-sectional study, 36 premenopausal women with SLE were classified as normal weight (NW,n = 16) or excess body weight (EBW, n = 20). Anthropometric, metabolic, dietary, and physical activity data were collected. Genome-wide DNA methylation in SAT was assessed using the Infinium HumanMethylationEPIC BeadChip.

Results: A total of 3783 differentially methylated CpG sites (DMCpGs) were identified between groups, with 1165 hypermethylated and 2618 hypomethylated sites in EBW patients. DMCpGs were enriched in promoter and open sea regions and annotated to immune, inflammatory, and metabolic pathways. DNMT1 expression was higher in EBW patients.

Conclusions: Excess body weight is associated with distinct DNA methylation patterns in SAT from patients with SLE.

Clinicaltrials: gov Identifier: NCT05097365.

Primary Sjögren's Syndrome (pSS) is a chronic, systemic autoimmune disease characterized by sicca symptoms due to exocrine gland involvement, but also presenting with a wide range of extraglandular manifestations and diverse subjective burdens, leading to significant clinical heterogeneity that complicates accurate diagnosis and objective assessment of disease activity. While transcriptome sequencing technologies have revolutionized the global analysis of alternative splicing (AS) events and aberrant AS has been implicated in the pathogenesis of various autoimmune diseases, research into AS in pSS remains limited to individual genes. Therefore, this study analyzed peripheral blood transcriptomes from pSS patients and healthy controls, utilizing key co-expression module eigengene values to stratify patients into homogeneous subgroups. Clear differential AS analysis was further obtained. Ten genes with significant AS events were identified, with AS in WARS1, OASL, DDX60, C2, RMI2, PALM2AKAP2, and MYO7B significantly associated with various laboratory indicators. Furthermore, by combining expression and usage rate changes with protein sequence structure predictions, their detailed functional implications in pSS were fully discussed. In conclusion, novel AS signatures significantly associated with pSS severity were revealed, which may serve as potential biomarkers for disease stratification and therapeutic targets in pSS, further providing opportunities for mechanistic research.

Interindividual epigenetic variability, particularly in DNA methylation, is now recognized as a significant contributor to phenotypic diversity in mammals including humans. These epivariable regions, which make up a small fraction of the genome, are strongly influenced by genetic factors and environmental factors, especially during early development. In this context, epigenetic variability of DNA methylation has been proposed as an adaptive force involved in various environmental responses. In fish and other vertebrates, environmental factors are known to influence the health, performance and welfare, likely through the alteration of the epigenetic landscape. However, whether interindividual epigenetic variability may contribute to the phenotypic plasticity of fishes is unknown. Here we provide a first description of the rainbow trout methylome interindividual variability using a whole-genome bisulfite sequencing approach in an isogenic line to minimize genetic variation. Variable methylation regions were identified in both liver and hypothalamus tissues of 12 replicate fishes and were found enriched at gene regulatory elements, such as promoters and first introns. Gene Ontology analysis revealed functional clusters related to cellular development, neural communication, metabolic balance, and immune response. Interestingly, some variably methylated regions are found at the same genomic loci in both tissues and showed a strong intraindividual correlation in methylation levels, suggesting establishment during early embryogenesis. Overall, our work demonstrates the existence of interindividual epigenetic variability in rainbow trout and provides valuable insights into the regulatory function of DNA methylation variation that is likely involved in developmental and physiological processes.

Musella lasiocarpa (MLA, 2n = 18, Musaceae) is an endangered species native to south-western China. We assembled its haplotype-resolved, telomere-to-telomere genomes with a genome size of 503.6 Mb consisting of 52.8% repetitive DNA. A 134 bp tandem repeat, Mlcen, was identified at all centromeres, and telomere sequences were present at 30 of 36 assembled pseudo-chromosome ends. The distal gene-rich regions display high synteny, whereas retrotransposon polymorphisms between haplotypes occurred throughout chromosomes, contributing to diversity. Phylogenetic analysis shows MLA diverged from Ensete 42 million years ago, and together they share a common ancestor with Musa. Among 35,312 protein-coding genes, 14 up-regulated and 34 down-regulated transcription factors were identified under cold treatment. This high-quality genomic resource advances our understanding of MLA chromosomal evolution characterized by structural variations, repetitive DNA dynamics, and cold-responsive genes at both haplotype and species levels; and enables genome-assisted improvement of more resilient crops such as bananas and Ensete.