BMC Biology最新文献

Background: Deep-diving cetaceans tolerate acute hypoxia better than their terrestrial ancestors and shallow-diving counterparts. However, our poor understanding of how genetic factors, cellular functions, and physiological characteristics combine to drive hypoxia adaptation in deep-diving cetaceans remains a critical gap.

Results: Here, we studied the genetic basis for this ability by creating a de novo genome assembly for the pygmy sperm whale (Kogia breviceps) and comparatively analyzing genomes from 12 cetacean species, including 2 other deep-diving cetaceans. We also sequenced and compared single-nucleus RNA data from the muscle and heart of the pygmy sperm whale and its terrestrial relative Bos taurus. We found that genetic and cellular changes in the HIF-1 pathway, electron transport chain, glucose and fatty acid catabolism, and heart rate may contribute to hypoxia tolerance in deep-diving cetaceans. Key adaptations include rapid evolution of glycolysis-related genes (PYGM and ENO3), differential expression of HIF-1 pathway genes like ARNT, and accelerated conserved noncoding elements in genes such as ATP5F1E (ATP synthase) and DMD (dystrophin). We found an increase in myocytes and type II cardiomyocytes in the pygmy sperm whale's muscle and heart tissues, which may support energy metabolism and homeostasis during deep dives.

Conclusions: These findings suggest deep-diving cetaceans have unique genetic and cellular adaptations to cope with hypoxia, offering insights into how mammals handle low oxygen levels at the cellular level.

Background: Maize, as an important dual-purpose grain and forage crop all over the world, exhibits extensive heritable and phenotypic diversity. Taking the breeding patterns as the core and developing advanced genetic breeding tools with the characteristics of Chinese maize germplasms will significantly advance the genetic dissection of complex agronomic traits and facilitate targeted genetic improvement in maize.

Results: Here, based on the predominant heterotic pattern "X group × SPT group," we developed the first whole chromosome substitution line (WCSL) population in maize, designated the MOSAIC population. We ensured the near-complete substitution of single chromosome and consistent genetic backgrounds as much as possible in each WCSL from the MOSAIC population. The de novo genome assembly and characteristic analysis of the parental lines revealed abundant genetic variants between WCSLs and their parents. Three key major QTL loci associated with tassel main axis length, anthocyanin accumulation at the base of anther glumes, and tassel branch number were rapidly identified and mapped using the MOSAIC population. Meanwhile, we established the MOSAIC molecular breeding and data sharing platform (MOSAIC-DB), which integrates diverse data resources including pedigrees, phenotypes, genotypes, assembled genomes, and structural variants along with integrated analysis modules.

Conclusions: This study provides a powerful new genetic resource for uncovering the genetic basis of complex traits and for genetic improvement, which facilitates the exploration of the molecular mechanisms underlying key agronomic traits and enables more directed breeding strategies by integrating genetics and genomics in maize.

Background: For most species, Aging is an inevitable biological process that poses significant challenges to global healthcare due to age-related diseases. Recent advances in peptide therapy have highlighted anti-aging peptides (AAPs) as a promising therapeutic strategy, owing to their low immunogenicity and ease of synthesis. However, the lack of computational tools for AAP identification has hindered systematic research in this field.

Results: In this study, we provided a benchmark dataset of anti-aging peptides (AAPs) based on their annotated biological functions and AgingBase database. Subsequently, we proposed three novel predictive models, including 1) Antiaging-FL, which integrates feature representation learning with machine learning algorithms; 2) ESM_GAN, which utilizes a generative adversarial network (GAN) for data augmentation to enhance prediction robustness; and 3) ESM_CNN, which combines a data augmentation strategy based on conservative amino acid substitutions with a convolutional neural network (CNN) architecture for improved feature extraction. Comprehensive evaluations demonstrated that all three models achieved high predictive performance. Specifically, Antiaging-FL achieved an AUC of 1.00 on the AAP400 dataset and 0.99 on an independent test set, while ESM_GAN yielded AUCs of 0.99 and 0.95, and ESM_CNN obtained AUCs of 0.96 and 0.94, respectively.

Conclusions: Our study presents three high-performance models for AAP prediction, accelerating the discovery of novel anti-aging peptides. These models not only provide a valuable resource for researchers but also offer insights into the functional mechanisms of AAPs, paving the way for targeted drug development in aging-related therapeutics.

Background: The role of cholesterol- and cholesterol crystal-mediated inflammation has been extensively investigated in circulating macrophages in the context of cardiovascular diseases while little is known about its contribution to lung diseases. However, lipid-laden alveolar macrophages and crystal-like structures have been reported in lungs of different human and animal models of lung diseases. In this study, we address the hypothesis that a mechanism of inflammasome activation, due to altered cholesterol metabolism, may occur also in alveolar macrophages.

Results: We tested the effect of soluble (cholesterol-enriched liposomes) and crystalized cholesterol exposure in a cell model of macrophages and in primary murine alveolar macrophages. Both soluble and crystalized cholesterol can be taken up by macrophages, mainly by phagocytosis for the crystals. Prolonged exposure to both forms of cholesterol leads to intracellular cholesterol accumulation in cytoplasmic lipid droplets and to foam cell formation in a time-dependent manner. However, in unprimed alveolar macrophages, immunofluorescence detection of the NLRP3 inflammasome and analysis of inflammatory cytokines showed that only cholesterol crystals stimulate the assembly of the inflammasome in speck and release of IL-18, indicating the sterile activation of the inflammasome. The role of NLRP3 was confirmed by chemical inhibition of the NLRP3 inflammasome in vitro and by validation in macrophages from NLRP3-deficient mice.

Conclusions: In alveolar macrophages, cholesterol crystals, but not soluble cholesterol, trigger the assembly and activation of the inflammasome, thus leading to the inflammasome-dependent release of IL-18. These results open new scenarios for the role of alveolar macrophages and of cholesterol-mediated inflammation in the lung.

Background: Migration is a microevolutionary process that shapes cultural, societal, and genetic diversity in human populations. While previous genetic studies have examined the effects of migrations in several key areas of the world, there is a paucity of such studies in the upper Greater Mekong Subregion (GMS). The upper GMS, encompassing northern Thailand, Laos, Myanmar, and southern China, has been a major corridor for human migration and interaction between East and Southeast Asian populations for thousands of years.

Results: We generated new genome-wide data for Tai-Kadai (TK)-speaking ethnic groups, namely Lue and Yong, from northern Thailand and integrated them with data from the upper GMS and across Asia. Our results highlight the genetic diversity among ethnic groups in the GMS, particularly the genetic continuity of TK migration from southern China to northern Thailand. The TK speakers in Thailand predominantly exhibit multiple ancestries from East Asia and Southeast Asia, with regional differentiations. The TK groups in northern Thailand primarily derive their genetic contributions from Dai-related communities, while northeastern Thai populations show a higher proportion of Lao-related ancestry. Those in central and southern Thailand display additional ancestries from other groups, such as Austroasiatic and South Asian populations. The genetic history of TK-speaking Lue populations illustrates the role of TK migration, founder effects, and historical resettlements in shaping genetic diversity.

Conclusions: Overall, analyses of genome-wide data reveal that the genetic background of TK speakers in Thailand is predominantly of East Asian origin, with additional contribution from Southeast Asian populations. This pattern supports the idea of sustained migration from southern China into Thailand, particularly concentrated in the northern part. Our findings reinforce the historical continuity of TK movements across the upper GMS and provide new insights into the genetic and cultural transformations that have shaped present-day Thai populations.

Background: Plant-parasitic nematodes (PPNs) pose a major threat to global agricultural production, yet fundamental research on their biology remains limited. The origin and evolutionary trajectory of PPNs remain elusive, largely due to the scarcity of chromosome-level genomic data. Among them, migratory PPNs are considered a key transitional form between free-living and obligate parasitic lifestyles, as they exhibit both plant parasitism and fungal feeding behaviors.

Results: In this study, we assembled a chromosome-level genome of the sweet potato rot nematode Ditylenchus destructor and confirmed the presence of four chromosomes through Hi-C scaffolding and karyotype analysis. Comparative genomic analysis with two others migratory PPNs, Bursaphelenchus xylophilus and Aphelenchoides besseyi, revealed that the Nigon elements in B. xylophilus are largely conserved with those of the model organism Caenorhabditis elegans, while D. destructor and A. besseyi exhibit extensive Nigon element rearrangements. These rearrangements were strongly correlated with patterns of protein sequence collinearity. Moreover, transcriptomic profiling across five developmental stages of D. destructor identified numerous stage-specific candidate secreted proteins, including putative effectors, and transcription factors. Functional analysis via RNA interference demonstrated that many of these genes play important roles in either embryonic development or parasitism.

Conclusions: Together, our results provide valuable genomic and transcriptomic resources for studying PPNs, uncovering critical insights into their genome evolution and parasitism-related gene functions, and laying a crucial foundation for advancing the understanding of PPN biology and their impact on agricultural systems.

Background: Two non-synonymous single-nucleotide polymorphisms (SNPs) rs61752561 (D95N substitution) and rs17632542 (I163T substitution) in the KLK3 gene encoding prostate-specific antigen (PSA), a chymotrypsin-like serine protease, are associated with prostate cancer risk and have been shown to reduce the activity of PSA. However, the structural impact of these SNPs on PSA, which may underlie the observed risk associations and functional alterations, has not been fully explored.

Results: Computational modelling predicted that the variants D95N and I163T do not cause drastic structural changes in PSA. However, molecular dynamics simulations suggested that while the two prominent loops of wild-type PSA remain tethered to their initial conformations over 500 ns of simulation, they are disrupted in both variants, leading to increased loop dynamics. Frustration analysis, normal mode analysis (NMA) and perturbation response scanning identified dynamic links between mutation sites and increased loop dynamics that trigger long-range conformational changes, disrupting the active site and potentially hindering catalytic activity. Thermal denaturation stability assays using recombinant protein show the impact of D95N and I163T substitution on the protein stability.

Conclusions: These data show that KLK3 SNPs disrupt dynamic communication of the key loops required for proteolytic activity of PSA, which may explain the association of these SNPs with prostate cancer risk and/or progression.

Background: Microbes are widespread from the marine surface to the hadal zones and play a significant role in global biogeochemical cycling. Physicochemical properties of hadal zone shift with depth, in turn influencing the distribution profiles, biogeochemical functions, and adaptative mechanisms of microbial communities in hadal trenches. However, the ecological functions and evolutions of microbial communities along the surface water down to the sediments in the Diamantina and Kermadec trenches have been rarely studied.

Results: Here, we provided a detailed metagenomic analysis of samples along the water columns (0-6553 m) and sediments (3060-9232 m) in the Diamantina and Kermadec trenches. The euphotic waters had a significantly higher ɑ-diversity than the deep-sea waters and sediments (p < 0.05, ANOSIM). Clear inter/intra-trench discrepancies of microbial communities along water layers appeared, with remarkable vertical connectivity exhibited in the Diamantina Trench (97.5%) than the Kermadec Trench (88.8%). Positive correlations among Proteobacteria, Bacteroidota, Actinobacteria, and Thaumarchaeota in seawaters and between Proteobacteria and Chloroflexi in sediments were revealed from the co-occurrence network. Niche-specific microbial groups showed distinct dominant metabolic pathways in carbon fixation, nitrogen, and sulfur cycles. Furthermore, we reconstructed 119 metagenome-assembled genomes (MAGs) of Rhodobacterales, and their notably low ratios of non-synonymous substitutions to synonymous substitutions (pN/pS, 0.23) and high carbon atoms per residue side chain (C-ARSC, 2.86) in deep-sea sediments suggested a pronounced selection critical for their survival.

Conclusions: We found a clear connectivity of microbial communities in vertical profile, and discrepancy existed between the Diamantina and Kermadec trenches; Rhodobacterales' evolutionary adaptation related to genomic features (pN/pS and SNVs/kbp) in the deep-sea trench environments. These findings provided new insights into the community succession and potential adaption mechanism along the water columns to sediments in deep trenches.

Background: Immunosenescence, particularly the altered ratio of naïve and memory T cells, contributes to a diminished immune reserve and impaired adaptive immunity in aging and frail populations. The role of TGF-β signaling pathway-a critical hallmark of organismal senescence and T-cell exhaustion-in terminally differentiated effector memory T (Temra) cells remains elusive. We devised single-cell and bulk-cell RNA sequencing (RNA-seq) datasets to identify age-group-specific transcriptional regulatory networks in T cells and elucidate the roles of TGF-β signaling constituents associated with immunosenescence in Temra.

Results: Analysis of scRNA-seq data from peripheral T cells across healthy human age groups revealed young-specific regulons controlled by FOXP1, TCF7, LEF1, and IKZF1 and old-specific regulons governed by EOMES, TBX21, RUNX3, and NFATC2. Transcription factor (TF)-binding-motif enrichment analysis implicated TGF-β signaling pathway components ZEB2 and TGFBR3 as pivotal target genes coregulated by multiple TFs, potentially facilitating T-cell terminal differentiation and exhaustion. Pseudotime analysis and bulk-cell RNA-seq further corroborated these regulons, validating their association with T-cell self-renewal capacity (young-specific) or effector/terminal differentiation (old-specific). In terms of aging, multiple TGF-β signaling activation components, including TGFB1, TGFBR1, SMAD3, ZEB2, and TGFBR3, were significantly upregulated in CD8 + Temra cells relative to CD8 + naïve T cells.

Conclusions: Our study used systematic approaches for delineating age-dependent transcriptional networks for T-cell-associated immunosenescence. We identified multiple components of the TGF-β signaling pathway as potential biomarkers of Temra, which are strongly associated with senescence features including impaired differentiation plasticity, high cytotoxicity, and inflammatory chemotaxis capacity.