Genomics最新文献_第4页

Elucidating the toxic mechanism of doxorubicin-induced cardiac ferroptosis through network toxicology and molecular docking 通过网络毒理学和分子对接研究阿霉素致心脏铁下垂的毒性机制。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-01 DOI: 10.1016/j.ygeno.2025.111185

Yu Liu , Song-heng He , Yu-xin Sun , Yi-wei Liu , Yu-ting Wang , Jian Xiong , Yun-nan Liu , Jiao Chen , Ming-sheng Sun , Fan-rong Liang

Doxorubicin (DOX), a widely utilized chemotherapeutic agent, is restricted in clinical application due to its cardiotoxicity, with ferroptosis being a pivotal factor in DOX-induced cardiotoxicity (DIC). DIC can be classified into chronic and acute types based on clinical manifestations. Both forms involve ferroptosis, yet the underlying mechanisms are still unclear. This study aimed to investigate the molecular mechanisms of DIC ferroptosis, including acute and chronic DIC, through network toxicology and molecular docking analysis, thereby proposing potential therapeutic targets. To achieve this, acute and chronic DIC models were established. A comprehensive assessment of cardiac function, myocardial injury, oxidative stress, and iron deposition was conducted. Transcriptome analysis uncovered distinct gene expression patterns and enrichment pathways related to ferroptosis in the two models. Key genes (POMC in chronic DIC, and SNCA and S100A8 in acute DIC) were pinpointed via intersection analysis with genes associated with cardiomyopathy and ferroptosis. Regulatory networks involving miRNAs and transcription factors were constructed. Potential therapeutic agents were predicted using molecular docking and subsequently validated. These findings deepened our understanding of the ferroptosis mechanisms in DIC and offered novel personalized therapeutic strategies for preventing and treating DIC.

多柔比星（Doxorubicin， DOX）是一种广泛应用的化疗药物，但由于其心脏毒性而限制了临床应用，其中铁下沉是DOX诱导的心脏毒性（DIC）的关键因素。DIC根据临床表现可分为慢性型和急性型。这两种形式都涉及铁下垂，但潜在的机制尚不清楚。本研究旨在通过网络毒理学和分子对接分析探讨DIC铁下垂的分子机制，包括急性和慢性DIC，从而提出潜在的治疗靶点。为此，建立了急性和慢性DIC模型。综合评估心功能、心肌损伤、氧化应激和铁沉积。转录组分析揭示了两种模型中与铁下垂相关的不同基因表达模式和富集途径。通过与心肌病和铁下垂相关基因的交叉分析，确定了关键基因（慢性DIC中的POMC，急性DIC中的SNCA和S100A8）。构建了涉及mirna和转录因子的调控网络。使用分子对接预测潜在的治疗药物，并随后验证。这些发现加深了我们对DIC中铁下垂机制的理解，并为DIC的预防和治疗提供了新的个性化治疗策略。

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引用次数: 0

Deciphering the optimal genomic selection (GS) strategy of alkalinity tolerance trait in spotted sea bass (Lateolabrax maculatus) 斑点黑鲈耐碱性性状的最佳基因组选择策略研究。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2026-01-01 DOI: 10.1016/j.ygeno.2025.111190

Yonghang Zhang , Chong Zhang , Cong Liu , Haishen Wen , Xin Qi , Kaiqiang Zhang , Hailiang Wang , Kuopeng Cui , Lingyu Wang , Donglei Sun , Yun Li

Breeding strains tolerant to saline-alkaline conditions was a promising strategy for advancing the development and utilization of saline-alkali water areas. Spotted sea bass (Lateolabrax maculatus), with characteristics of broad salinity tolerance, was a favorable candidate for saline-alkaline tolerant strain. In this study, genotype data involved three markers (SNPs, InDels and SVs) and phenotype data from 287 individuals was used to construct the optimal genomic selection (GS) system. The results showed that significantly greater prediction accuracy was achieved using the GWAS-information mark selection strategy in comparison to the random selection strategy, particularly under 0.1 k density conditions (mean accuracy: 0.30 vs. 0.02). In terms of model, Bayesian models (mean accuracy:0.33) were more suitable than machine learning models (mean accuracy:0.29) for GS of alkalinity tolerance trait in spotted sea bass. Maximum predictive accuracies were attained with 100 SNPs, 600 InDels, and 12,800 SVs, where the BayesB model demonstrated consistently higher performance, yielding accuracies of 0.47, 0.41, and 0.53, respectively. Additionally, the use of combined markers resulted in higher prediction accuracy than any single marker type alone, particularly “SNP + InDel + SV” combination, which achieved an accuracy of up to 0.71. We have successfully established the GS system for alkalinity tolerance traits in spotted sea bass, providing valuable reference for the breeding of stress tolerance traits in other fish species.

选育耐盐碱菌株是推进盐碱区开发利用的有效途径。斑点海鲈鱼（Lateolabrax maculatus）具有广泛的耐盐性，是耐盐碱品系的有利候选品种。本研究利用287个个体的基因型数据（snp、InDels和SVs）和表型数据构建了最优基因组选择（GS）系统。结果表明，与随机选择策略相比，使用gwas -信息标记选择策略获得了更高的预测精度，特别是在0.1 k密度条件下（平均精度：0.30 vs. 0.02）。在模型方面，贝叶斯模型（平均精度：0.33）比机器学习模型（平均精度：0.29）更适合斑点黑鲈耐碱性性状的GS。在100个snp、600个InDels和12,800个sv的情况下，BayesB模型的预测精度达到了最高，分别为0.47、0.41和0.53。此外，使用组合标记比单独使用任何单一标记类型具有更高的预测精度，特别是“SNP + InDel+SV”组合，其准确率高达0.71。我们成功建立了斑点黑鲈耐碱性性状的GS体系，为其他鱼类耐胁迫性状的选育提供了有价值的参考。

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引用次数: 0

Genetic analysis of blood traits and stress resistance in Kirghiz sheep 柯尔克孜羊血液性状及抗逆性遗传分析。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-12-30 DOI: 10.1016/j.ygeno.2025.111189

Yanhao Li , Yuwei Peng , Ruizhi Yang , Lingfeng Kong , Lijun Zhu , Fumin Kou , Jialei He , Shudong Liu

The Kirghiz (KIR) sheep is a native sheep breed adapted to the extreme ecological environment of the Pamir Plateau. To explore the genetic mechanisms underlying its environmental adaptability, we collected whole-genome resequencing data from 100 KIR sheep and high-density genomic chip data from 509 individuals across 12 breeds. The genetic diversity of the population was evaluated through the inbreeding coefficient (F), nucleotide diversity (π), and linkage disequilibrium (LD). Subsequently, we performed genome-wide association studies (GWAS) on 13 blood traits in KIR populations and identified key environmentally adaptive genes through selective sweeps. The results indicate that while the KIR population exhibits high genetic diversity, its inbreeding coefficient is increasing, reflecting a lack of systematic breeding and improvement. GWAS identified 21 key genes (e.g., IL11, TRPC6, CASP9) significantly associated with blood traits for the first time. Selective sweep analysis identified multiple candidate genes (e.g., THSR, NF1, and MITF) involved in regulating environmental adaptability. Enrichment analysis and functional annotation further elucidated the potential mechanisms of these candidate genes in environmental adaptation. Our study provides a crucial scientific foundation for conserving genetic resources and implementing adaptive breeding strategies for this valuable local breed.

柯尔克孜羊是适应帕米尔高原极端生态环境的本地绵羊品种。为了探索其环境适应性的遗传机制，我们收集了100只KIR羊的全基因组重测序数据和12个品种509只羊的高密度基因组芯片数据。通过近交系数(F)、核苷酸多样性（π）和连锁不平衡（LD）评价群体的遗传多样性。随后，我们对KIR人群的13个血液特征进行了全基因组关联研究（GWAS），并通过选择性扫描确定了关键的环境适应性基因。结果表明，KIR群体具有较高的遗传多样性，但近交系数呈上升趋势，缺乏系统的育种和改良。GWAS首次鉴定出与血液性状显著相关的21个关键基因（如IL11、TRPC6、CASP9等）。选择性扫描分析确定了多个参与调节环境适应性的候选基因（如THSR、NF1和MITF）。富集分析和功能注释进一步阐明了这些候选基因在环境适应中的潜在机制。本研究为保护这一珍贵的地方品种的遗传资源和实施适应性育种策略提供了重要的科学依据。

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引用次数: 0

Transcriptome-wide isoform and promoter remodeling in DM1 fibroblasts uncovered by long-read RNA sequencing 长读RNA测序揭示DM1成纤维细胞转录组全异构体和启动子重塑

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-12-16 DOI: 10.1016/j.ygeno.2025.111175

Xinbo Ji , Rui Zhang , Didi Shan , Tongwei Shi , Yingxin Wang , Yao Tang , Zexin Zhan , Yichang Jiao , Hongxu Wang , Jianing Li , Dongdong Wang , Jingwen Xu , Chuanzhu Yan , Fuchen Liu

Myotonic dystrophy type 1 (DM1) is characterized by sequestration of RNA-binding proteins and widespread transcriptomic dysregulation, yet isoform-level transcriptomic landscapes remain incompletely defined. Here, we performed integrated long-read (PacBio Iso-Seq) and short-read (Illumina RNA-seq) profiling of primary fibroblasts from DM1 patients and healthy controls. Long-read sequencing identified >15,000 transcript isoforms in DM1 fibroblasts, revealing extensive alternative splicing and novel transcript discovery beyond short-read resolution. Isoform-switching analysis uncovered 104 significant events, particularly affecting signaling and cytoskeletal pathways, independent of gene-level expression changes. Differential promoter usage further highlighted transcriptional rewiring, with 106 dysregulated promoters, over two-thirds of which were previously unannotated. Moreover, systematic splicing analysis detected >1200 significantly altered events, predominantly alternative first exons, converging on extracellular matrix remodeling and muscle contractility pathways. Together, these data provide an isoform-resolved landscape of DM1 fibroblasts, demonstrating that transcript-level remodeling-including alternative splicing, isoform switching, and promoter dysregulation-constitutes a critical regulatory layer underlying DM1 pathogenesis.

肌强直性营养不良1型（DM1）的特征是rna结合蛋白的隔离和广泛的转录组失调，但同型水平的转录组景观仍然不完全确定。在这里，我们对来自DM1患者和健康对照的原代成纤维细胞进行了整合的长读（PacBio Iso-Seq）和短读（Illumina RNA-seq）分析。长读测序在DM1成纤维细胞中鉴定出bbbb15000个转录异构体，揭示了广泛的选择性剪接和超越短读分辨率的新转录物发现。异构体转换分析揭示了104个重要事件，特别是影响信号传导和细胞骨架通路，独立于基因水平表达变化。差异启动子的使用进一步突出了转录重连接，106个启动子失调，其中超过三分之二的启动子之前未被注释。此外，系统剪接分析发现>1200显著改变事件，主要是替代第一外显子，聚集在细胞外基质重塑和肌肉收缩途径上。总之，这些数据提供了DM1成纤维细胞的异构体解析图，证明转录水平的重塑——包括选择性剪接、异构体开关和启动子失调——构成了DM1发病机制的关键调控层。

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引用次数: 0

Whole-transcriptome analysis of TCM effects on growth and immune regulation in Pelodiscus sinensis via coding and non-coding RNAs 中药通过编码rna和非编码rna对黄芪生长和免疫调节作用的全转录组分析。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-12-15 DOI: 10.1016/j.ygeno.2025.111171

Xin Zhang , Xiuhong Cai , Shirui Yue , Zhangxuan Chen , Mingsong Xiao

Integrating Traditional Chinese Medicines (TCMs) into Pelodiscus sinensis aquaculture offers a promising alternative to conventional treatments. Through whole-transcriptome analysis, this study investigated the effects of TCMs on growth and immune regulation, uncovering a complex interplay between coding and non-coding RNAs. We identified three key subsets of differentially expressed genes (DEGs): SpTG1 (low-dose-specific DEGs), SpTG2 (high-dose-specific DEGs), and TG1_TG2 (DEGs common to both low and high doses). These DEG subsets were significantly enriched in pathways pivotal for growth, metabolism, and immunity, such as the PI3K-Akt, TNF, and AMPK signaling pathways. Our findings clarify roles of miRNAs, circRNAs, and lncRNAs in mediating TCM responses, with their potential interactions in competing endogenous RNA (ceRNA) networks suggesting novel regulatory targets. These results position TCMs as sustainable and eco-friendly feed additives. Further research into the specific mechanisms identified here could enable the development of targeted strategies to boost P. sinensis fitness and yield.

将中药整合到中国黄参水产养殖中是一种很有前途的替代传统治疗方法。本研究通过全转录组分析，研究了中药对生长和免疫调节的影响，揭示了编码rna和非编码rna之间复杂的相互作用。我们确定了差异表达基因（DEGs）的三个关键亚群：SpTG1（低剂量特异性DEGs）， SpTG2（高剂量特异性DEGs）和TG1_TG2（低剂量和高剂量共同的DEGs）。这些DEG亚群在生长、代谢和免疫的关键通路中显著富集，如PI3K-Akt、TNF和AMPK信号通路。我们的研究结果阐明了miRNAs、circRNAs和lncRNAs在中医药应答中的作用，它们在竞争的内源性RNA （ceRNA）网络中的潜在相互作用提示了新的调控靶点。这些结果表明中药是可持续和环保的饲料添加剂。进一步研究这一特定的机制，将有助于开发有针对性的策略来提高中华白杨的适合度和产量。

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引用次数: 0

Lineage-specific expansion and functional divergence of β-keratin genes underlying shell evolution in turtles 海龟壳进化中β-角蛋白基因的谱系特异性扩增和功能分化。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-12-13 DOI: 10.1016/j.ygeno.2025.111174

Mengrao Chen , Yannan Gao , Chenkai Li , Fang Li , Feiyang Zhang , Wei Sun , Chutian Ge , Zongji Wang

β-Keratins are key structural proteins that contribute to the formation of keratinized epidermal structures such as scales, feathers, and shells in reptiles and birds. However, the evolutionary diversification and functional specialization of β-keratins in turtles remain poorly understood. Here, we combined comparative genomic, structural, and transcriptomic analyses across 10 turtle species representing five families, alongside four outgroup species (birds, crocodilians, lizards, and snakes), to systematically investigate the evolution of β-keratin genes in Testudines. We identified 835 β-keratin genes in turtles, which clustered into two major evolutionary lineages: conserved, non-specific β-keratins within the epidermal differentiation complex (EDC) and lineage-specific β-keratins located outside the EDC. Notably, these turtle-specific β-keratins were absent in squamates but shared evolutionary origins with avian feather keratins. Domain and protein structure analyses revealed that hard-shelled turtles retain β-keratins with conserved β-sheet structures and glycine–tyrosine enrichment, likely associated with shell rigidity. In contrast, soft-shelled turtles exhibit reduced β-sheet content and transcriptional silencing of these genes. Transcriptomic and semi-quantitative PCR further confirmed carapace-specific expression of turtle-specific β-keratins in hard-shelled turtles, but not in soft-shelled species. Together, our findings demonstrate that the expansion, structural modification, and tissue-specific expression of β-keratin genes underlie the evolutionary divergence of shell phenotypes in turtles, providing new insights into the molecular basis of epidermal adaptation and morphological innovation in reptiles.

β-角蛋白是关键的结构蛋白，有助于形成角化的表皮结构，如爬行动物和鸟类的鳞片、羽毛和贝壳。然而，海龟β-角蛋白的进化多样化和功能特化仍然知之甚少。在这里，我们结合比较基因组学、结构和转录组学分析，包括5个科的10种海龟，以及4个外群物种（鸟类、鳄鱼、蜥蜴和蛇），系统地研究了鳖类中β-角蛋白基因的进化。我们在海龟中鉴定了835个β-角蛋白基因，这些基因聚集在两个主要的进化谱系中：表皮分化复合体（EDC）内的保守的非特异性β-角蛋白和位于EDC外的谱系特异性β-角蛋白。值得注意的是，这些海龟特有的β-角蛋白在鳞片中不存在，但与鸟类羽毛角蛋白有共同的进化起源。结构域和蛋白质结构分析表明，硬壳龟保留了β-角蛋白，具有保守的β-片结构和甘氨酸-酪氨酸富集，可能与壳刚性有关。相比之下，软壳龟表现出β-sheet含量减少和这些基因的转录沉默。转录组学和半定量PCR进一步证实了海龟特异性β-角蛋白在硬壳龟中有甲壳特异性表达，而在软壳龟中没有。总之，我们的研究结果表明，β-角蛋白基因的扩展、结构修饰和组织特异性表达是海龟壳表型进化分化的基础，为爬行动物表皮适应和形态创新的分子基础提供了新的见解。

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引用次数: 0

OCm7G: An interpretable one-class predictor for m7G methylation sites trained with limit negative samples OCm7G：用极限阴性样本训练的m7G甲基化位点的可解释的一类预测器。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-12-11 DOI: 10.1016/j.ygeno.2025.111173

Fei Li , Jinbang Qin , Zhaomin Yao , Yiping Xu , Yabing Zhu , Yan Wang , Lan Huang , Wenxuan Luo , Zhiguo Wang , Fengfeng Zhou

N7-methylguanosine (m7G) is a common RNA modification linked to multiple diseases. Accurate detection of m7G sites is vital for elucidating its biological roles, but conventional methods are often laborious and costly. AI-based approaches offer alternatives, yet most rely on balanced datasets, ignoring real-world imbalances where negative samples vastly outnumber positives. This discrepancy may lead to overestimated model performance. To address this, we reconstructed independent test sets with low positive-to-negative ratios and benchmarked various models. We propose OCm7G, an ensemble of one-class classifiers with hierarchical thresholding. OCm7G achieves performance comparable to state-of-the-art methods on balanced sets and surpasses them in highly imbalanced scenarios, despite using only 52.5 % of the training data. Moreover, OCm7G offers interpretable predictions, aiding researchers in understanding model decisions. The source code and datasets are publicly available at: https://github.com/lidaosheng/OCm7G.

n7 -甲基鸟苷（m7G）是一种与多种疾病相关的常见RNA修饰。准确检测m7G位点对于阐明其生物学作用至关重要，但传统方法往往既费力又昂贵。基于人工智能的方法提供了替代方案，但大多数依赖于平衡的数据集，忽略了现实世界的不平衡，即负样本数量远远超过正样本。这种差异可能导致高估模型性能。为了解决这个问题，我们重建了具有低正负比的独立测试集，并对各种模型进行了基准测试。我们提出了OCm7G，一个具有分层阈值的单类分类器的集合。OCm7G在平衡集上实现了与最先进的方法相当的性能，并在高度不平衡的场景中超越了它们，尽管只使用了52.5 %的训练数据。此外，OCm7G提供了可解释的预测，帮助研究人员理解模型决策。源代码和数据集可以在：https://github.com/lidaosheng/OCm7G上公开获取。

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引用次数: 0

Transcriptomic analysis of distinct mantle regions in yellow- and black-shelled Asian clam (Corbicula fluminea): Identification of genes associated with Shell biomineralization and pigment deposition 亚洲黄壳和黑壳蛤不同地幔区的转录组学分析：壳生物矿化和色素沉积相关基因的鉴定。

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-12-09 DOI: 10.1016/j.ygeno.2025.111172

Xueyan Ma , Lujie Wen , Dongpo Xu , Wu Jin , Haibo Wen , Huaishun Shen

Corbicula fluminea exhibits two distinct shell color morphs: yellow and black. This study reveals molecular mechanisms behind shell color variation in the Asian clam C. fluminea (yellow vs. black morphs) through comparative transcriptomics of edge/central mantle tissues. Transcriptome assembly identified 24, 174 annotated genes and 2, 234 novel genes. Comparative analyses revealed 238 common differentially expressed genes (DEGs) shared between the YC vs YE and BC vs BE comparisons, along with 575 DEGs in BC vs YC and 460 DEGs in BE vs YE. Transcriptomic profiling demonstrated that Biomineralization genes (calcium/organic matrix-related) showed region-specific expression, driving shell formation. Melanogenesis pathway enrichment and pigmentation genes (tyrosinase, calmodulin, sulfotransferase) may play an important role in pigmentation in C. fluminea. This study expands our understanding of shell biomineralization and pigment deposition in C. fluminea, providing important insights into the genetic and biochemical regulation of shell diversity in bivalves.

Corbicula fluminea呈现出两种不同的外壳颜色：黄色和黑色。本研究通过边缘/中心地幔组织的转录组学比较揭示了亚洲蛤（黄色与黑色变种）壳颜色变化背后的分子机制。转录组组装鉴定出24174个注释基因和2234个新基因。比较分析显示，YC与YE和BC与BE比较共有238个共同差异表达基因（DEGs）， BC与YC共有575个，BE与YE共有460个。转录组学分析表明，生物矿化基因（钙/有机基质相关）表现出区域特异性表达，驱动壳的形成。黑素生成途径富集和色素沉着基因（酪氨酸酶、钙调素酶、硫转移酶）可能在氟藻色素沉着中起重要作用。本研究扩大了我们对C. fluminea贝壳生物矿化和色素沉积的认识，为双壳类贝壳多样性的遗传和生化调控提供了重要的见解。

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引用次数: 0

Differences in chromatin accessibility and gene expression associated with growth performance in Pacific whiteleg shrimp, Litopenaeus vannamei 凡纳滨对虾（Litopenaeus vannamei）生长性能相关的染色质可及性和基因表达差异

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-12-07 DOI: 10.1016/j.ygeno.2025.111170

Bo Ma , Yang Liu , Xin Zhang , Jiayue Yin , Yanhong Wang , Lvping Zhang , Ting Chen , Yugang Wu , Chaoqun Hu , Peng Luo

Litopenaeus vannamei is a species of significant economic importance. In this study, we applied ATAC-seq and RNA-seq to compare shrimp from super-fast growth (SFG) and slow growth (SG) groups to investigate the mechanisms underlying growth performance. Chromatin accessibility was higher in the SFG group than SG group, and a total of 765 differentially accessible regions (DARs) were identified. Promoter-associated analysis of DARs-related genes revealed their predominant involvement in energy metabolism and cell proliferation. Transcriptome analysis indicated that genes related to molting and light reception may contribute to growth performance. Integrated analysis of ATAC-seq and RNA-seq data suggested that chromatin accessibility likely influences growth performance by modulating gene expression in key metabolic pathways, including amino acid metabolism, lipid metabolism, and immunity function. Additionally, LvNAGase was identified as a candidate gene regulating growth performance in L. vannamei.

凡纳滨对虾是一种具有重要经济价值的物种。在本研究中，我们采用ATAC-seq和RNA-seq对超高速生长（SFG）组和慢速生长（SG）组对虾进行了比较，以探讨其生长性能的机制。SFG组的染色质可及性高于SG组，共鉴定出765个差异可及区（dar）。dars相关基因的启动子相关分析显示，它们主要参与能量代谢和细胞增殖。转录组分析表明，与蜕皮和光接受相关的基因可能对生长性能有影响。ATAC-seq和RNA-seq数据的综合分析表明，染色质可及性可能通过调节氨基酸代谢、脂质代谢和免疫功能等关键代谢途径中的基因表达来影响生长性能。此外，LvNAGase被确定为调节南美l.s annamei生长性能的候选基因。

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引用次数: 0

Remodeling of Staphylococcus epidermidis genome over three decades of nosocomial exposure 三十年医院暴露对表皮葡萄球菌基因组的重塑

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics

Pub Date : 2025-12-06 DOI: 10.1016/j.ygeno.2025.111167

Joana Rolo , Ana Botelho , Diana Espadinha , Peder Worning , Rita Sobral , Henrik Westh , Maria Miragaia

Staphylococcus epidermidis recently emerged as a major cause of medical device-associated infections. However, the role of the nosocomial environment in its evolution remains poorly understood. To investigate the genomic changes underlying S. epidermidis evolutionary history, we compared genomes of 1960s isolates, before its recognition as a human pathogen, to those from the 1990s, when it became prevalent in hospital-acquired infections.

We found that S. epidermidis from the 1960s and 1990s shared similar population structures, with the A/C cluster predominating in both periods. Recombination was frequent, particularly in the A/C cluster, and occurred throughout the chromosome. Alterations in the mobile genetic elements of the 1990s isolates caused a drastic genomic change, characterized by phage loss, and staphylococcal cassette chromosome elements and insertion sequences acquisition. The 1990s isolates gained multiple antibiotic resistance and virulence genes, which are associated with biofilm formation and persistence. Genomic analysis of the orfX/rmlH vicinity revealed differences between the two groups of isolates. The 1960s isolates harbored a complex orfX/rmlH vicinity containing multiple SCC and pseudoSCC, and genes with high homology to SCCmecIV, while the 1990s isolates contained only SCCmec and ACME. Interestingly, one early isolate carried a disrupted mecA, within a pseudoSCCmecIV, suggesting it may represent a precursor to the contemporary SCCmecIV.

Our results showed that prolonged exposure to the hospital environment drove S. epidermidis genomic remodeling, including the accumulation of genes linked to antibiotic resistance, enhanced colonization, biofilm formation, genome plasticity, and the loss of bacteriophages –contributing to its success as a persistent nosocomial pathogen.

表皮葡萄球菌最近成为医疗器械相关感染的主要原因。然而，医院环境在其演变中的作用仍然知之甚少。为了研究表皮葡萄球菌进化史背后的基因组变化，我们比较了20世纪60年代表皮葡萄球菌被识别为人类病原体之前分离株的基因组，以及20世纪90年代表皮葡萄球菌在医院获得性感染中流行的基因组。结果表明，20世纪60年代和90年代的表皮葡萄球菌种群结构相似，均以A/C集群为主。重组是频繁的，特别是在A/C集群，并发生在整个染色体。20世纪90年代分离的葡萄球菌可移动遗传元件的改变引起了剧烈的基因组变化，其特征是噬菌体丢失，葡萄球菌盒式染色体元件和插入序列获得。20世纪90年代分离的菌株获得了多种抗生素抗性和毒力基因，这些基因与生物膜的形成和持久性有关。orfX/rmlH附近的基因组分析显示两组分离株之间存在差异。20世纪60年代分离的菌株含有一个复杂的orfX/rmlH邻近区，包含多个SCC和伪SCC，以及与SCCmecIV高度同源的基因，而90年代分离的菌株仅含有SCCmec和ACME。有趣的是，一个早期分离物在伪SCCmecIV中携带了一个断裂的mecA，这表明它可能是当代SCCmecIV的前身。我们的研究结果表明，长期暴露在医院环境中会导致表皮葡萄球菌基因组重塑，包括与抗生素耐药性相关的基因积累、定植增强、生物膜形成、基因组可塑性和噬菌体的丧失，这些都有助于表皮葡萄球菌成功成为一种持久性的医院病原体。

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引用次数: 0