BMC Biology最新文献

{"title":"TAD conservation in vertebrate genomes is driven by stabilising selection.","authors":"Fabiana Patalano, Simen Rød Sandve, Rein Aasland, Jonas Paulsen","doi":"10.1186/s12915-025-02362-0","DOIUrl":"10.1186/s12915-025-02362-0","url":null,"abstract":"<p><strong>Background: </strong>Topologically associating domains (TADs) are fundamental structural and gene regulatory components of chromatin defined by regions of high intra-domain contact frequency. Though TADs are found across diverse metazoans, the extent of their evolutionary conservation is still debated.</p><p><strong>Results: </strong>Here, we investigated the evolutionary conservation of TADs by analysing Hi-C data from 12 vertebrate species. We examined TAD numbers, borders, and gene positioning within TADs. We found that TAD features are all highly conserved across species, but decrease with evolutionary distance. Nevertheless, modelling TAD evolution using Ornstein-Uhlenbeck (OU) process revealed strong stabilising selection signatures for TAD number within the majority of syntenic blocks. These syntenic blocks under selection were enriched for highly conserved noncoding elements associated with developmental gene regulation (genomic regulatory blocks). However, strong signatures for stabilising selection for TAD numbers were also found independent of genomic regulatory blocks or genes with non-developmental functions.</p><p><strong>Conclusions: </strong>These findings improve our understanding of TAD conservation and highlight stabilising selection as an important driver in 3D genome evolution. Although selection on TAD structures is pronounced for developmental genes, our findings highlight the importance of TADs in genome and organismal functions beyond developmental biology.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"241"},"PeriodicalIF":4.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphology and mechanical behavior of diatoms in wet and dry states studied using nano-XCT.","authors":"Qiong Li, Jürgen Gluch, Zhongquan Liao, André Clausner, Przemysław Dąbek, Ehrenfried Zschech","doi":"10.1186/s12915-025-02341-5","DOIUrl":"10.1186/s12915-025-02341-5","url":null,"abstract":"<p><strong>Background: </strong>Diatoms are widely studied biological objects because of their large variety of geometric shapes and their unique physical and chemical properties. They survive widely in nature within moisture. Imaging the diatoms three dimensionally in moisture and correlating their mechanical behavior is an interesting and challenging topic.</p><p><strong>Results: </strong>Here, the morphology and mechanical properties of diatoms were studied in wet state and then in dry state. A customized sample holder was integrated into a laboratory transmission X-ray microscope to image the morphology changes and volume shrinkage of the diatom while transitioning from the wet to the dry state. The measured volume shrinkage of a single diatom cell of Actinocyclus sp. is about 0.16. By performing an in-situ micromechanical experiment in both states, the maximal loading force of a single Actinocyclus sp. was determined until cracking appeared and compared in both states. This value is in the range of several hundred µN in the wet state and single-digit mN in the dry state. The normalized stiffness of the studied diatoms is significantly higher in the dry state than in the wet state. 2D radiograph and 3D tomography imaging of the diatoms reveal the different locations for crack propagation in both states.</p><p><strong>Conclusions: </strong>Our study supplies the important imaging method, the structure and functional information of the diatoms for future studies on diatoms in moisture but also in dry state. This information can help design bio-inspired materials and even in the development of bio-sustainable materials.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"239"},"PeriodicalIF":4.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ephrin-B2 deletion in GABAergic neurons induces cognitive deficits associated with single-nucleus transcriptomic differences in the prefrontal cortex.","authors":"Peijun Ju, Yu Fang, Siying Xiang, Weidi Wang, Ying Sun, Wei Wang, Yanli Ding, Chao Luo, Ping Jiang, Jianhua Chen","doi":"10.1186/s12915-025-02333-5","DOIUrl":"10.1186/s12915-025-02333-5","url":null,"abstract":"<p><strong>Background: </strong>Ephrin-B2 (EB2) signaling plays a crucial role in regulating memory and synaptic plasticity. Comprehensive identification of cell-type-specific transcriptomic changes in EB2 knockout mice is expected to shed light on potential mechanisms associated with EB2 signaling in cognitive functions.</p><p><strong>Results: </strong>Our study captures changes in cell populations in response to EB2 manipulation and reveals previously uncharacterized cell types (CPA6 + inhibitory neurons) in the mPFC. We validated the differential transcriptomic activity of Pbx1 and Meis1 in CPA6 + neurons using fluorescence in situ hybridization (ISH) in EB2-vGATCre mice. The aberrant presence of CPA6 + neurons in the mPFC may correlate with cognitive impairments induced by EB2 deletion in vGAT + neurons. Analyzing differentially expressed genes (DEGs) in individual cell clusters, we identified alterations related to synapse organization and development, cognition, amyloid-beta formation, and locomotor behavior. Additionally, our DEGs overlapped with human genome-wide association study (GWAS) candidate genes related to cognition and anxiety, underscoring the relevance of our mouse model to human disease.</p><p><strong>Conclusions: </strong>We present a comprehensive atlas of cell-type-specific gene expression changes in this synaptic deficiency model and identify novel cell-type-specific targets implicated in cognitive deficits. Our investigation provides a detailed map of the cell types, genes, and pathways altered in this inhibitory synaptic deficiency model.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"242"},"PeriodicalIF":4.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kazakh Tobet dogs in the genomic landscape: refining the history of livestock guardian breeds.","authors":"Anastassiya Perfilyeva, Kira Bespalova, Yelena Kuzovleva, Mamura Begmanova, Almira Amirgaliyeva, Olga Vishnyakova, Inna Nazarenko, Sergey Bespalov, Assel Zhaxylykova, Arailym Yerzhan, Kanagat Yergali, Yuliya Perfilyeva, Rustam Mussabayev, Zhassulan Zhaniyazov","doi":"10.1186/s12915-025-02344-2","DOIUrl":"10.1186/s12915-025-02344-2","url":null,"abstract":"<p><strong>Background: </strong>Despite the growing body of research on livestock guarding dog (LGD) breeds, Central Asian LGDs remain significantly underrepresented in genetic studies. Additionally, while some research has explored the genetic basis of selective traits in LGDs, significant gaps remain. By investigating the genetic diversity, evolutionary history, and adaptive traits of the Kazakh Tobet, a Central Asian LGD breed from Kazakhstan, we aim to contribute to a deeper understanding of the genetic basis that characterizes LGD breeds.</p><p><strong>Results: </strong>We analyzed the genetic relatedness of Kazakh Tobet dogs by combining SNP data from 90 unrelated Kazakh Tobets with publicly available SNP data from 124 dogs from 17 LGD breeds, 1753 dogs from 140 non-LGD breeds, 551 free-ranging dogs, and 16 wolves. The Kazakh Tobets exhibit considerable genetic diversity. Phylogenetic and PCA analyses suggest a common genetic origin with LGDs from Central and West Asia, which was complicated by gene flow from European LGDs. Signs of introgression from East Asian and Arctic non-LGDs may indicate a historical or modern gene exchange affecting the Kazakh Tobet lineage. Genetic clustering with free-ranging dogs supports the idea that open breeding systems do not compromise the functional integrity of LGD traits. Selection scans identified eight genomic regions with 127 genes associated with cognitive function, immune response, and metabolic regulation, suggesting the evolutionary importance of these traits in Kazakh Tobets.</p><p><strong>Conclusions: </strong>This study provides new insights into the genetic history of LGD breeds and their connections to the broader genetic landscape of non-LGD breeds.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"240"},"PeriodicalIF":4.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate prediction of drug-protein interactions by maintaining the original topological relationships among embeddings.","authors":"Yanfei Li, Xiran Chen, Shuqin Wang, Jinmao Wei","doi":"10.1186/s12915-025-02338-0","DOIUrl":"10.1186/s12915-025-02338-0","url":null,"abstract":"<p><strong>Background: </strong>Learning-based methods have recently demonstrated strong potential in predicting drug-protein interactions (DPIs). However, existing approaches often fail to achieve accurate predictions on real-world imbalanced datasets while maintaining high generalizability and scalability, limiting their practical applicability.</p><p><strong>Results: </strong>This study proposes a highly generalized model, GLDPI, aimed at improving prediction accuracy in imbalanced scenarios by preserving the topological relationships among initial molecular representations in the embedding space. Specifically, GLDPI employs dedicated encoders to transform one-dimensional sequence information of drugs and proteins into embedding representations and efficiently calculates the likelihood of DPIs using cosine similarity. Additionally, we introduce a prior loss function based on the guilt-by-association principle to ensure that the topology of the embedding space aligns with the structure of the initial drug-protein network. This design enables GLDPI to effectively capture network relationships and key features of molecular interactions, thereby significantly enhancing predictive performance.</p><p><strong>Conclusions: </strong>Experimental results highlight GLDPI's superior performance on multiple highly imbalanced benchmark datasets, achieving over a 100% improvement in the AUPR metric compared to state-of-the-art methods. Additionally, GLDPI demonstrates exceptional generalization capabilities in cold-start experiments, excelling in predicting novel drug-protein interactions. Furthermore, the model exhibits remarkable scalability, efficiently inferring approximately <math><mrow><mn>1.2</mn> <mo>×</mo> <msup><mn>10</mn> <mn>10</mn></msup> </mrow> </math> drug-protein pairs in less than 10 h.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"243"},"PeriodicalIF":4.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive light flickering reinstates visual plasticity in adult mice via lipocalin 2.","authors":"Chenchen Ma, Zhenni Wang, Wei Wu, Xiao Ma, Laijian Wang, Xinxin Zhang, Wenjing Chen, Xi Kuang, Yufei Li, Ying Miao, Tian Xue, Bin Jiang, Yupeng Yang","doi":"10.1186/s12915-025-02360-2","DOIUrl":"10.1186/s12915-025-02360-2","url":null,"abstract":"<p><strong>Background: </strong>Light flickering, a non-invasive stimulation technique over recent years, has shown a promising therapeutic potential for brain dysfunctions. However, the mechanisms by which this visual stimulus exerts its beneficial effects are largely unknown.</p><p><strong>Results: </strong>Here, we found that 7 days of 1 h 20 and 40 Hz light flickering promoted visual plasticity in primary visual cortex of adult mice. RNA sequencing results showed an increase in lipocalin 2 (LCN2) expression in the visual cortex following 20 or 40 Hz light flickering. By contrast, 80 Hz light flickering or constant light had no significant effect on either plasticity or LCN2 expression. LCN2 knock-down blocked light flickering-induced plasticity, while its overexpression mimicked the effects of light flickering. Moreover, the administration of minocycline blocked the plasticity induced by either light flickering or LCN2 overexpressing. Lastly, 40 Hz light flickering combined with reverse suture facilitated the recovery of the abnormal ocular dominance distribution in adult amblyopic mice.</p><p><strong>Conclusions: </strong>Our data indicate that non-invasive light flickering restores visual plasticity, mediated by LCN2 and microglia, providing new insights into the mechanism of light flickering.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"237"},"PeriodicalIF":4.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification of leg mobility in the Burgess Shale Olenoides serratus indicates functional differences between trilobite and xiphosuran appendages.","authors":"Sarah R Losso, Karma Nanglu, Walker C Weyland, Javier Ortega-Hernández","doi":"10.1186/s12915-025-02335-3","DOIUrl":"10.1186/s12915-025-02335-3","url":null,"abstract":"<p><strong>Background: </strong>Euarthropod appendages are specialized for diverse roles including feeding, walking, and mating, which require precise morphologies and ranges of motion. Cambrian fossils preserve exceptional details of extinct euarthropod appendages that can illuminate their anatomy and ecology. However, fossils are typically restricted by small sample sizes or incomplete preservation, and thus functional studies of the appendages usually rely on idealized reconstructions. The Burgess Shale Olenoides serratus is unique among trilobites owing to the availability of numerous specimens with soft tissue preservation that allow us to quantify its appendages' functional morphology.</p><p><strong>Results: </strong>We measured the range of motion of the legs in Olenoides serratus and the extant horseshoe crab Limulus polyphemus. Despite repeated ecological comparisons between trilobites and xiphosurans, we find significant differences in the appendages' mobility between these taxa, with Limulus showing greater flexibility between the podomeres.</p><p><strong>Conclusions: </strong>O. serratus legs have a more restricted range of motion relative to L. polyphemus, particularly in their distal region. Flexure between the protopodite played a critical role in allowing the endopodite to create known trilobite trace fossils and bring food toward the ventral groove.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"238"},"PeriodicalIF":4.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A CD24⁺CD271⁺ melanoma cancer stem cell possesses hybrid characteristics of its single marker counterparts and promotes invasion and therapeutic resistance.","authors":"Olivia Knowles, Patricio Doldan, Isabella Hillier-Richardson, Sophia Lunetto, Stephanie Lunt, Gehad Youssef, Luke Gammon, Ian C Mackenzie, Michael P Philpott, Hasan Rizvi, Daniele Bergamaschi, Catherine A Harwood, Adrian Biddle","doi":"10.1186/s12915-025-02336-2","DOIUrl":"10.1186/s12915-025-02336-2","url":null,"abstract":"<p><strong>Background: </strong>An important role for phenotype switching has been demonstrated in metastasis and therapeutic resistance of both melanoma and epithelial tumours. Phenotype switching in epithelial tumours is driven by a minority cancer stem cell (CSC) sub-population with lineage plasticity, but such a sub-population has not been identified in melanoma. We investigated whether cell surface markers used to identify CSCs in epithelial tumours could identify a CSC sub-population with lineage plasticity in melanoma.</p><p><strong>Results: </strong>We identified a CD24⁺CD271⁺ minority sub-population in melanoma that possesses the stem cell characteristics of lineage plasticity and self-renewal. This population displayed hybrid characteristics, combining the attributes of discrete CD24⁺CD271^- and CD24^-CD271⁺ cellular sub-populations but with heightened sphere formation, lineage plasticity, migratory ability and drug resistance over its single-marker counterparts. CD24⁺CD271^- and CD24⁺CD271⁺ stem cell sub-populations were observed in 10% of human melanomas, mainly at the invasive front. They were also found in human tumour scRNAseq datasets, where they expressed genes associated with stem cells and therapeutic resistance. The CD24^-CD271⁺ sub-population, on the other hand, shared expression of epithelial-mesenchymal transition (EMT) genes with the CD24⁺CD271⁺ sub-population.</p><p><strong>Conclusions: </strong>The lack of CD24⁺CD271^- and CD24⁺CD271⁺ stem cells in the majority of human melanoma specimens led us to conclude that they may be dispensable for melanoma progression. Nevertheless, the enhanced sphere formation, lineage plasticity, migratory ability and drug resistance of the CD24⁺CD271⁺ sub-population may signal a contextual requirement for these stem cells when melanomas face challenging environments both clinically and in experimental systems.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"235"},"PeriodicalIF":4.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of protein-protein interaction based on interaction-specific learning and hierarchical information.","authors":"Tao Tang, Taiguang Shen, Jing Jiang, Weizhuo Li, Peng Wang, Sisi Yuan, Xiaofeng Cao, Yuansheng Liu","doi":"10.1186/s12915-025-02359-9","DOIUrl":"10.1186/s12915-025-02359-9","url":null,"abstract":"<p><strong>Background: </strong>Prediction of protein-protein interactions (PPIs) is fundamental for identifying drug targets and understanding cellular processes. The rapid growth of PPI studies necessitates the development of efficient and accurate tools for automated prediction of PPIs. In recent years, several robust deep learning models have been developed for PPI prediction and have found widespread application in proteomics research. Despite these advancements, current computational tools still face limitations in modeling both the pairwise interactions and the hierarchical relationships between proteins.</p><p><strong>Results: </strong>We present HI-PPI, a novel deep learning method that integrates hierarchical representation of PPI network and interaction-specific learning for protein-protein interaction prediction. HI-PPI extracts the hierarchical information by embedding structural and relational information into hyperbolic space. A gated interaction network is then employed to extract pairwise features for interaction prediction. Experiments on multiple benchmark datasets demonstrate that HI-PPI outperforms the state-of-the-art methods; HI-PPI improves Micro-F1 scores by 2.62%-7.09% over the second-best method. Moreover, HI-PPI offers explicit interpretability of the hierarchical organization within the PPI network. The distance between the origin and the hyperbolic embedding computed by HI-PPI naturally reflects the hierarchical level of proteins.</p><p><strong>Conclusions: </strong>Overall, the proposed HI-PPI effectively addresses the limitations of existing PPI prediction methods. By leveraging the hierarchical structure of PPI network, HI-PPI significantly enhances the accuracy and robustness of PPI predictions.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"236"},"PeriodicalIF":4.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dokdo sea lion Zalophus japonicus genome reveals its evolutionary trajectory before extinction.","authors":"Jungeun Kim, Asta Blazyte, Jae-Pil Choi, Changjae Kim, Fedor Sharko, Sungwon Jeon, Eun-Mi Kim, Hawsun Sohn, Jong Hee Lee, Hyun Woo Kim, Mi Hyun Yoo, Kyunglee Lee, Artem Nedoluzhko, Jong Bhak","doi":"10.1186/s12915-025-02351-3","DOIUrl":"10.1186/s12915-025-02351-3","url":null,"abstract":"<p><strong>Background: </strong>The Dokdo sea lion (Zalophus japonicus), commonly referred to as Gangchi in Korea and the Japanese sea lion internationally, was endemic to the Northwest Pacific before its extinction in the 1950s. However, its origins, speciation, and genetic diversity remain poorly understood.</p><p><strong>Results: </strong>To address this, we sequenced DNA from 16 Z. japonicus bone fragments, obtained from Dokdo and Ulleungdo islands in Korea. Our genome-wide SNP analyses reveal Z. japonicus as the earliest diverged species within its genus, redefining its evolutionary relationship with the California (Z. californianus) and Galapagos (Z. wollebaeki) sea lions. Our research further elucidates the phylogeny of Z. japonicus, shedding light on the complexity of the genetic isolation process within its genus that was prompted by the geographic isolation of the three populations of Zalophus ancestral stock. Conversely, the genetic signature of the Dokdo sea lion genome can be modeled as an evolutionary pathway involving gene flow from Otariidae species with shared range. In addition, we discovered that the population decline of Z. japonicus started already over 100,000 years ago; however, Z. japonicus genome maintained a relatively high heterozygosity despite nearing extinction.</p><p><strong>Conclusions: </strong>Our genome-scale analysis sheds light on the phylogeny of Z. japonicus, the evolutionary pathways underlying its speciation, and its genetic diversity before extinction. Broadly, we elucidate Zalophus gene flow complexity and genetic diversities among extant species. Furthermore, this study offers retrospective genomic insights into the extinction process of a carnivorous marine mammal, information that could aid conservation efforts for extant Otariidae species.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"234"},"PeriodicalIF":4.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}