BMC Genomics最新文献

Background: Heat stress (HS) is a growing environmental factor impacting the growth and medicinal value of plateau medicinal plants due to global climate change. Plant heat shock factors (HSFs) are key transcriptional regulators in HS responses, yet the mechanisms of HSFs in plateau medicinal plants remain largely unexplored.

Results: In this study, we identified 17 HSF genes from the plateau medicinal plant Fritillaria cirrhosa D.Don. All FcHSF members were divided into two different phylogenetic groups. Moreover, the distribution of conserved motifs among these genes reveals subfamily-specific divergence. PCR-based cloning was further used to amplify two transcript variants of FcHSFA1, designated as FcHSFA1a and FcHSFA1b, which display distinct tandem repeat configurations at their C-termini regions. Both variants were upregulated under HS, with FcHSFA1b showing higher expression. Subcellular localization showed both variants in the nucleus and cytoplasm of tobacco epidermal cells. FcHSFA1b exhibited stronger transcriptional activation activity than FcHSFA1a in yeast cells. Overexpression of both variants in tobacco enhanced HS-related gene expression, increased peroxidase activity and chlorophyll content, and thereby improved thermotolerance.

Conclusions: These findings suggest that FcHSFA1 variants contribute to heat tolerance, with distinct transcriptional responses, offering strategies to enhance basal thermotolerance in F. cirrhosa.

The rapid evolution of viral antigens poses a major challenge to infectious disease control, particularly for pathogens like influenza that undergo frequent antigenic changes. While deep mutational scanning and platforms such as Nextstrain have advanced our understanding of mutation effects and population-level viral dynamics, they often rely on strain-level analyses that may overlook key within-strain antigenic changes. In this study, we adopted a site-based approach to systematically identify and analyze hemagglutinin (HA) mutations in influenza viruses that differed from vaccine strains, using publicly available genomic data. We found that nonsynonymous mutations exhibiting vaccine-associated allele frequency changes were significantly enriched in epitope regions in both pH1N1 and H3N2, and that pH1N1 showed a higher proportion of rapid allele-replacement events occurring within a single influenza season, whereas H3N2 substitutions more often occurred across multiple seasons. Geographically, several mutations displayed allele frequency changes correlated with local vaccination coverage. Phylogenetic analyses further revealed that five nonsynonymous mutations in H3N2 arose independently across multiple clades. Serological assays confirmed reduced neutralization for multiple pH1N1 mutations, and computational protein stability analyses indicated that observed mutations tended to increase protein stability in both subtypes, and that in pH1N1, potential epitope mutations were more stabilizing than those in non-epitope regions. By integrating bioinformatics with experimental validation, our approach provides a refined understanding of how selective pressures shape antigenic evolution at the site level, which could aid future studies on vaccine effectiveness and epidemic trends.

Protein post-translational modifications (PTMs) represent a core regulatory mechanism governing protein function and cellular fate. Their dynamic alterations profoundly influence critical biological processes. However, Existing research primarily focuses on single-PTM site prediction and remains confined by single-modality analysis. This study introduces UniGraphPTMs, the first universal PTM site prediction framework based on multimodal fusion and graph neural networks. UniGraphPTMs employs a master-slave architecture to break branch independence through multi-stage interactions. We pioneer the integration of the protein structure pre-training model Saprot with ProtT5 and ESM-C, enabling comprehensive exploration of protein sequence-structure multimodal embeddings. The master branch utilizes xLSTM and Mamba for sequence feature extraction, while the slave branch innovatively constructs a Hierarchical Graph Neural Network for multi-level structural feature extraction. To optimize cross-modal interactions, a novel Low-Rank Cross-Attention Bidirectional Gating fusion module is designed. Furthermore, by incorporating a hierarchical contrastive loss function and pioneering a dual-modality adaptive weighting mechanism, we effectively address the challenge of synergistic learning across multiple losses. Evaluated across 11 datasets encompassing 6 distinct PTM types, UniGraphPTMs outperforms all previous models, demonstrating average improvements of 3.27% in AUC, 4.31% in MCC, and 3.94% in AP. Furthermore, we conducted a proof-of-concept study on multi-PTM joint prediction.

Background: The projected 2.7-fold increase in population in sub-Saharan Africa by the end of the century demands consideration as to how agricultural output can keep pace. Augmenting nitrogen inputs is a practical necessity, but this must be accomplished in such a way that avoids the environmental costs of past advances and also places the resource in the hands of those who will be the most affected. Biological nitrogen fixation might play an important role. The realization that certain algae are able to provide for their own nitrogen needs by fixing atmospheric N₂ raises the possibility that an endosymbiont responsible for the nitrogen might be transferred to crop plants. For this to take place, it is necessary that the endosymbionts be (or be made to be) sufficiently independent of their hosts so that they may establish themselves in crop plants appropriate to African agriculture.

Results: Genomes from six endosymbionts from diatoms within the family Rhopalodiaceae were analyzed. They were compared to genomes from free-living cyanobacteria and to those of the nitroplast UCYN-A and chromatophore from Paulinella, to which they are related. Unlike the latter two endosymbionts, the six from Rhopalodia encode all the enzymes considered that underlie metabolic processes and provide the energy to power N-fixation. Some of the endosymbionts also appear able to synthesize cofactors essential for central metabolism. The analysis points to possible carbon sources the endosymbionts might take up from their hosts, including glycerol and chitobiose. Possible routes of nitrogen export to the host were also examined.

Conclusions: Within the limits of genome analysis, some of the Rhopalodian endosymbionts appear to be metabolically independent of their hosts, except for requiring a carbon source. However, the choice of carbon source and the likely means of nitrogen export are not compatible with crop plants. Genetic modification would surely be necessary for any prospect of propagation of an endosymbiont in a plant of agricultural importance, and significant questions must first be answered in the laboratory. To this end, the endosymbiont of Epithemia clementina may be best suited for such investigations, eventually after transfer to the model diatom Phaeodactyllum tricornutum.

Background: Interferon-γ (IFNγ) is a key cytokine that activates macrophages and is essential for the defence against intracellular pathogens. Beyond its immediate effects, IFNγ also shapes macrophages for subsequent encounters with pathogen-associated molecules by multiple mechanisms, including chromatin remodelling. Here, we employed integrated epigenomic and transcriptomic approaches utilizing primary macrophages from gene-modified mice to explore the role of STAT1 and its naturally occurring isoforms in these processes.

Results: Using ChIP-seq for histone modifications (H3K27ac and H3K4me1) and RNA-seq, we demonstrate that STAT1 isoforms differentially modulate macrophage responses to lipopolysaccharide (LPS) following IFNγ conditioning. We provide genetic evidence that STAT1 isoforms exhibit distinct capacities to mediated IFNγ-induced changes in H3K27 acetylation at promoter and enhancer regions, thereby shaping transcriptional responses to LPS. We show that the STAT1β isoform, which lacks the C-terminal transactivation domain (TAD), is unable to mediate the repressive effect of IFNγ on transcriptional regulation by LPS but retains significant collaborative activity. Furthermore, we show that IFNγ attenuates the induction of a subset of antiviral genes and represses LPS-induced negative feedback loops, thereby amplifying the inflammatory response to pathogens. These effects are dependent on the presence of the STAT1 C-terminal TAD, highlighting its importance in fine-tuning the balance between inflammatory and antiviral responses.

Conclusions: Our findings uncover isoform-specific roles of STAT1 in IFNγ-driven epigenetic regulation and macrophage conditioning, providing new insights into the control of inflammation and innate immunity.

Enterocytozoon bieneusi (E. bieneusi) is a pathogenic microsporidian that affects immunocompromised individuals, including those with HIV, and represents a major cause of diarrhea. It can severely impact human health, causing gastrointestinal disease, nutritional deficits, and life-threatening complications. However, the microbial mechanisms by which E. bieneusi affects host nutrition are not well understood. Wild rodents have long been considered valuable models for studying human diseases due to similarities in gut microbiota dynamics and immune responses, making them particularly relevant for investigating parasitic infections. Here, we assembled a comprehensive catalog of 9,929 non-redundant microbial genomes from wild rodent gut metagenomes and evaluated their potential for B vitamins and vitamin K₂ biosynthesis using comparative functional genomics. We identified 2,307 genomes encoding complete pathways for de novo biosynthesis of at least one essential vitamin, though no single genome encoded all pathways, indicating a distributed metabolic capacity within the microbial community. Infection with E. bieneusi significantly altered the microbial composition and the potential for vitamin biosynthesis, with a notable expansion of Methanobacteriota and reprogramming of pyridoxine (vitamin B₆) biosynthesis pathways. These changes reveal a functional shift in microbial metabolism in response to parasitic pressure. By elucidating the microbial basis of vitamin biosynthesis in wild rodents and the impact of E. bieneusi infection on microbial functions, this study provides new insights into the role of gut microbiota in maintaining host health and supporting nutrient provision under parasitic stress. Moreover, the findings will provide valuable insights into the prevention and control of E. bieneusi infection in a variety of host, including humans.