BMC Biology最新文献

Background: The degeneracy of the genetic code is increasingly recognized for roles in regulating translation rate, protein folding, and cell response. However, the functional genomics of codon usage patterns remains poorly defined. We previously showed that prokaryotic and eukaryotic cells respond to individual stresses by uniquely reprogramming the tRNA pool and the dozens of tRNA modifications comprising the tRNA epitranscriptome to cause selective translation of mRNAs from codon-biased stress response genes. Here, we tested the hypothesis that functional gene families have distinct values of codon bias in the Saccharomyces cerevisiae genome by modeling isoacceptor codon distributions using a new approach-analysis of synonymous codon signatures (ASCS).

Results: Application of ASCS to the S. cerevisiae genome revealed linear relationships between patterns of codon bias and gene function using canonical correlation analysis. By mapping codon-biased open reading frames (ORFs) onto a functional network of gene ontology (GO) categories, we identified 91 gene families distinguished by unique codon usage signatures. The codon usage patterns were found to strongly predict functional clusters of genes, such as translational machinery, transcription, and metabolic processes.

Conclusions: The ASCS-derived model of codon usage patterns in S. cerevisiae reveals functional codon bias signatures and captures more biologically meaningful information when compared to other codon analytical approaches.

Background: Anticancer peptides (ACPs) are promising therapeutic agents with selective cytotoxicity toward cancer cells and minimal toxicity toward normal cells. However, the experimental identification and characterization of ACPs are often costly, time-consuming, and inefficient. Computational approaches provide promising alternatives for the rapid and accurate prediction of ACPs.

Results: Here, we introduce Aegis, a novel transformer-based deep learning framework designed for precise ACP identification. We systematically evaluated various machine learning and deep learning models via multiple feature extraction methods, including the composition of k-spaced amino acid pairs (CKSAAP), CTD composition (CTDC), CTD transition (CTDT), CTD distribution (CTDD), and pseudo amino acid composition (PAAC) methods. Comprehensive feature importance analyses via analysis of variance (ANOVA), ReliefF, and SHapley Additive exPlanations (SHAP) methods were performed, followed by incremental feature selection (IFS) to determine the optimal subset of discriminative features. Using the 103 optimal features identified via SHAP, Aegis achieves state-of-the-art (SOTA) performance on an independent testing dataset, outperforming existing ACP prediction models. Furthermore, compositional analysis revealed that ACP sequences are significantly enriched in positively charged and hydrophobic residues.

Conclusions: Overall, our study demonstrates the exceptional potential of transformer-based deep learning for ACP identification, laying a foundation for future computational screening and the clinical development of novel ACPs.

Background: Several intercellular signalling pathways (including wingless (Wnt), hedgehog (Hh), and bone morphogenetic protein (BMP)) are used repeatedly in animals throughout development and evolution and are also frequent targets for disease-associated disruptions. We have previously shown that the major transcriptional effectors of β-catenin-dependent Wnt signalling, the TCF/LEF proteins, in contrast to other pathway components, have a higher gene number and isoform diversity in vertebrates versus invertebrates, but this increased diversity has only been poorly quantified. Considering that isoform diversity correlates with organism complexity, any increase in major signalling effectors is likely to have made a significant contribution to vertebrate evolution.

Results: Using de novo long-read transcriptomes, we compared isoform number per gene for the chordates Ciona intestinalis, Lampetra planeri and Xenopus tropicalis, thus encompassing the invertebrate sister group to vertebrates, as well as a cyclostome and a gnathostome vertebrate. We find a significant increase in the number of transcript isoforms per gene expressed during embryo development and organogenesis at the invertebrate-to-vertebrate transition, specifically for the main transcription factor effectors of the Wnt/β-catenin, Hh and BMP pathways, i.e. TCF/LEF, GLI and SMAD.

Conclusions: Our results implicate an increase in isoform diversity of the transcription factors of major intercellular signalling pathways as having a disproportionate role in the evolutionary origin and diversification of vertebrates.

Background: Serial dependence, the influence of prior experience on current perception or decision, has typically been studied in static, perceptual contexts. Here, we investigate whether serial dependence reflects not just passive carryover but feedback-based updating of internal models, and how this process varies with autistic traits. In an immersive virtual reality penalty-kick task, participants kicked a ball that disappeared mid-flight and estimated its landing position. By laterally displacing the ball upon reappearance, we introduced trial-by-trial prediction errors.

Results: We found that individuals with higher autistic traits showed larger prediction deviations, indicating mis-calibrated forward predictions. At the same time, their responses were more strongly shaped by those priors, and unlike lower autistic traits individuals, they did not down-weight reliance when distortions were maximal. This pattern suggests reduced flexibility in updating prediction use: priors were both less accurate and more rigidly applied. Classical stimulus and response history biases were unaffected by autistic traits, highlighting a specific impairment in prediction updating. Football experts, by contrast, combined low directional updating with near-zero prediction consistency, suggesting robust mappings that resist transient perturbations.

Conclusions: These findings suggest that serial dependence in dynamic tasks reflects not only prediction formation but the flexible (or rigid) deployment of those predictions in the face of changing feedback. Our results highlight a distinctive rigidity in prediction weighting, rather than a general perceptual bias, in individuals with elevated autistic traits, and reveal contrasting stabilization strategies in domain experts.

Background: Interspecific hybridization is a fundamental evolutionary process, yet it often results in male sterility due to genomic incompatibilities and disrupted epigenetic regulation. While fertility variation among hybrids is increasingly acknowledged, the precise mechanisms linking these molecular disruptions to reproductive outcomes in vertebrates remain underexplored.

Results: To address this, we investigated testicular chromatin dynamics and gene expression in 19 mature male F₁ hybrids derived from a paternal bluntnose black bream (Megalobrama amblycephala, BSB) and a maternal topmouth culter (Culter alburnus, TC). These two species diverged approximately 12.74 million years ago, and their F₁ hybrid offspring display a wide range of fertility. Our integrative multi-omics analysis revealed several insights into the molecular basis of hybrid fertility. Genes inherited from the BSB parent exert a disproportionate influence on reproductive outcomes, indicating an asymmetric parental contribution. Furthermore, chromatin architecture analysis showed that BSB-derived enhancer-promoter networks are characterized by longer interaction distances and greater regulatory strength, suggesting distinct subgenome-specific topologies. Then, our analysis identified the BSB-derived gene LOC125267388 as a critical regulator of fertility. Homologous to a retrotransposon esterase and containing conserved teleost motifs, this gene likely contributes to the epigenetic modulation of hybrid fertility.

Conclusions: These findings provide insights into the chromatin-mediated mechanisms underpinning reproductive barriers in vertebrate hybrids, contributing to a deeper understanding of evolutionary divergence and hybrid incompatibility.

Background: Host immunity plays an important role in coral symbiosis with dinoflagellates. Photosymbiosis (the association between hosts and photosynthetic endosymbionts) has evolved multiple times within animals, e.g. within acoels, which are soft-bodied marine invertebrates whose immunity remains so far undescribed.

Results: Our predicted proteome searches show that acoels lack major signal transduction pathways usually involved in animal immunity. Their loss in acoels predates the occurrence of photosymbiosis in this clade. Immune challenges with the coral pathogen and bleaching agent, Vibrio coralliilyticus, increase acoel mortality and decrease symbiont abundance in adults of the photosymbiotic acoel Convolutriloba macropyga. Mortality in aposymbiotic C. macropyga juveniles or aposymbiotic species Hofstenia miamia is not affected. Ultrastructural studies of immune-challenged animals by transmission electron microscopy show damages at the cellular and organelle level, as well as a degradation of potential pathogens by the host. In situ hybridisation and differential gene expression analysis point to some areas of interaction between pattern recognition receptors and microbes, as well as to the involvement of acoel-specific or uncharacterised genes.

Conclusions: Based on our findings, photosymbiosis evolution in acoels could have been favoured by the loss of immune signalling pathways. Photosymbiosis in acoels seems to increase susceptibility to pathogen exposure and is disrupted by pathogens. Our data also suggests phagocytosis of pathogens and the possibility of a novel molecular immune response specific to acoels.

Background: Tyrosine sulfation is a widespread posttranslational modification in mammals and is known to influence protein function and signaling. However, its functional significance during porcine preimplantation development remains poorly understood.

Results: In this study, we demonstrate that TPST2-mediated tyrosine sulfation is critical for early porcine embryonic development. TPST2 is transcriptionally activated during zygotic genome activation by its antisense long noncoding RNA, termed aTPST2, which recruits MED4, a core subunit of the Mediator complex, to activate TPST2 transcription in cis. Mechanistically, TPST2 mediates sulfation at tyrosine 39 (Y39) of TTYH3, enhancing its protein stability. The stabilized TTYH3 interacts with RAP1B to activate MAPK signaling, thereby ensuring proper embryonic development.

Conclusions: Our findings elucidate a compelling molecular mechanism by which tyrosine sulfation orchestrates porcine preimplantation development. Together, these results provide new insights into the developmental functions of tyrosine sulfation.

Background: The dynamic change of N6-methyladenosine (m⁶A) modification on substrate RNA molecules plays a critical role in different biological processes and disease pathogenesis. Although the beneficial effects of exercise training (ET) on skeletal muscle insulin resistance (IR) are well-established, the contribution of RNA m⁶A modification in ET-related adaptations in high-fat diet (HFD)-induced IR remains unclear.

Results: In this study, we show that exercise stimulation triggers a dynamic shift in skeletal muscle m⁶A modification levels during HFD consumption. As a key m⁶A methyltransferase, METTL16 was downregulated in HFD-fed mice and upregulated by ET at both the mRNA and protein levels. In vitro, METTL16 knockdown disrupted mitochondrial ultrastructure, reduced electron transport chain complex activities, and decreased the NAD⁺/NADH ratio, ATP content, and mitochondrial membrane potential, indicating impaired mitochondrial function. Concomitantly, METTL16 loss lowered m⁶A on PGC-1α mRNA, reducing its stability and protein abundance and blunting insulin signalling, whereas PGC-1α overexpression partially reversed these defects.

Conclusions: In conclusion, METTL16 functions as an exercise-responsive m⁶A methyltransferase that may modulate PGC-1α, mitochondrial function, and insulin-related signalling in HFD skeletal muscle, implicating the METTL16-m⁶A-PGC-1α axis in exercise-induced metabolic adaptations.

Background: In the wild, mice are subject to changes in light intensity and spectrum (colour) across the solar day. In addition, mice are able to self-modulate their light exposure - a concept termed light sampling behaviour, which results in intermittent patterns of light exposure. These complexities are poorly considered in most laboratory animal housing. As such, our understanding of the role of intermittent exposure to naturally-occurring changes in intensity and spectrum in circadian behaviour are limited. To address these issues we simulated both daylight and twilight in the laboratory, and provided a dark nestbox to enable behavioural regulation of light exposure.

Results: The results show that gradual changes in light intensity are a key driver of crepuscular light sampling in mice, whilst demonstrating for the first time that spectral cues at twilight modulate the timing of behaviour - advancing locomotor activity by 0.5h and light sampling behaviour by 1.1h.

Conclusions: Collectively, our results demonstrate the significance of changes in intensity and spectrum across twilight for regulating mouse behaviour. These findings highlight important differences in mouse behaviour under naturalistic environments compared to normal laboratory conditions.

How insect brains differ between the sexes and respond to sex-specific pheromones is still not well understood. Here we briefly exposed female Bicyclus anynana butterflies to wild type and modified male sex pheromone blends, previously shown to modify females' sexual preferences, and examined how their brains were modified at the morphological and molecular levels 3 days later. First, we 3D-reconstructed male and female brains of this species and explored changes in the size of the 67 glomeruli present in the olfactory lobe. Then we showed that one glomerulus changed in volume after a blend exposure, potentially implicating it in sex pheromone perception. Finally, we found that a few genes were differentially expressed but many more were differentially spliced between male and female naïve brains, and between naive and pheromone blend-exposed brains. These code for primarily calcium-binding channel proteins and RNA-binding proteins, respectively. A learned preference for changed levels in a single pheromone component was linked to different protein isoforms involved in synaptic transmission. Our work shows that naïve male and female brains differ primarily in gene splicing patterns and that a brief, 3-min, exposure to pheromones produces slight changes in brain volume and large changes in the splicing of genes involved in neural development, which correlate with changes in sexual preferences in females.