BMC Biology最新文献

{"title":"iVAE: an interpretable representation learning framework enhances clustering performance for single-cell data.","authors":"Zeyu Fu, Chunlin Chen, Song Wang, Junping Wang, Shilei Chen","doi":"10.1186/s12915-025-02315-7","DOIUrl":"10.1186/s12915-025-02315-7","url":null,"abstract":"<p><strong>Background: </strong>Variational autoencoders (VAEs) serve as essential components in large generative models for extracting latent representations and have gained widespread application in biological domains. Developing VAEs specifically tailored to the unique characteristics of biological data is crucial for advancing future large-scale biological models.</p><p><strong>Results: </strong>Through systematic monitoring of VAE training processes across 31 public single-cell datasets spanning oncological and normal conditions, we discovered that reducing the <math><mi>β</mi></math> value which corresponds to lower disentanglement of VAE significantly improves unsupervised clustering metrics in single-cell data analysis. Based on this finding, we innovatively developed iVAE with an irecon module that, when benchmarked against 8 established dimensionality reduction methods across 5 clustering performance metrics, exhibited superior capabilities in representing single-cell transcriptomic data.</p><p><strong>Conclusions: </strong>The proposed iVAE architecture enhances the interpretability of single-cell data compared to conventional VAE architectures as measured by clustering metrics. Our work establishes a potential foundational VAE architecture for developing specialized large-scale generative models for biological applications.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"213"},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636278","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 target genes and functional types of cis-regulatory modules in the human genome reveals their distinct properties.","authors":"Sisi Yuan, Pengyu Ni, Zhengchang Su","doi":"10.1186/s12915-025-02313-9","DOIUrl":"10.1186/s12915-025-02313-9","url":null,"abstract":"<p><strong>Background: </strong>Cis-regulatory modules (CRMs) such as enhancers and silencers play critical roles in virtually all biological processes by enhancing and repressing, respectively, the transcription of their target genes in specific cell types. Although numerous CRMs have been predicted in genomes, identifying their target genes remains a challenge due to low quality of the predicted CRMs and the fact that CRMs often do not regulate their closest genes.</p><p><strong>Results: </strong>We developed a method - correlation and physical proximity (CAPP) by leveraging our recently predicted 1.2 M CRMs in the human genome. CAPP is able to not only predict the CRMs' target genes but also their functional types using only chromatin accessibility (CA) and RNA-seq data in a panel of cell/tissue types plus Hi-C data in a few cell types. Applying CAPP to a panel of only 107 cell/tissue types with CA and RNA-seq data available, we predict target genes for 14.3% of the 1.2 M CRMs, of which 1.4% are predicted as both enhancers and silencers (dual functional CRMs), 98.2% as exclusive enhancers, and 0.4% as exclusive silencers. Dual functional CRMs tend to regulate more distant genes than exclusive enhancers and silencers. Enhancers tend to cooperate with other enhancers, whereas silencers typically act independently. Silencers preferentially regulate genes expressed across many cell/tissue types, while enhancers are prone to regulate genes expressed in fewer cell/tissue types.</p><p><strong>Conclusions: </strong>CAPP represents a significant advancement in predicting target genes and functional types of CRMs, especially dual functional CRMs, and different types of CRMs show distinct properties.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"211"},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636220","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":"BertADP: a fine-tuned protein language model for anti-diabetic peptide prediction.","authors":"Xueqin Xie, Changchun Wu, Yixuan Qi, Shanghua Liu, Jian Huang, Hao Lyu, Fuying Dao, Hao Lin","doi":"10.1186/s12915-025-02312-w","DOIUrl":"10.1186/s12915-025-02312-w","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is a global metabolic disease that urgently calls for the development of new and effective therapeutic agents. Anti-diabetic peptides (ADPs) have emerged as a research hotspot due to their therapeutic potential and natural safety, representing a promising class of functional peptides for diabetic management. However, conventional computational approaches for ADPs prediction mainly rely on manually extracted sequence features. These methods often lack generalizability and perform poorly on short peptides, thereby hindering effective ADPs discovery.</p><p><strong>Results: </strong>In this study, we introduce a fine-tuning strategy of large-scale pre-trained protein language models (PLMs) for ADPs prediction, enabling automated extraction of discriminative semantic representations. We established the most comprehensive ADPs dataset to date, comprising 899 rigorously curated non-redundant ADPs and 67 newly collected potential candidates. Based on three model construction strategies, we developed 11 candidate models. Among them, BertADP (a fine-tuned ProtBert model) demonstrated superior performance in the independent test set, outperforming existing ADPs prediction tools with an overall accuracy of 0.955, sensitivity of 1.000, and specificity of 0.910. Notably, BertADP exhibited remarkable sequence length adaptability, maintaining stable performance across both standard and short peptide sequences.</p><p><strong>Conclusions: </strong>BertADP represents the first PLMs-based intelligent prediction tool for ADPs, whose exceptional identification capability will significantly accelerate anti-diabetic drug development and facilitate personalized therapeutic strategies, thereby enhancing precision diabetes management. Furthermore, the proposed approach provides a generalizable framework that can be extended to other bioactive peptide discovery studies, offering an innovative solution for bioactive peptide mining.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"210"},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636277","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":"Organic cation transporter 3 on neuronal mitochondria mediates MPP⁺-induced mitochondrial dysfunction and neurotoxicity in a TIMM22-dependent manner.","authors":"Ao Guan, Sida Han, Suzhen Liang, Weiwei Shen, Min Guo, Mei Cui","doi":"10.1186/s12915-025-02318-4","DOIUrl":"10.1186/s12915-025-02318-4","url":null,"abstract":"<p><strong>Background: </strong>Mitochondria play crucial roles in cellular metabolism, and metabolite compartmentalization significantly impacts mitochondrial function and disease pathophysiology. MPP⁺ accumulation in mitochondria, a key factor in MPTP-induced neurodegeneration, leads to mitochondrial dysfunction, such as respiratory chain inhibition, ultimately leading to neuronal death. However, the mechanisms underlying mitochondrial MPP⁺ accumulation remain poorly understood. Organic cation transporter 3 (OCT3), a passive transporter mediating MPP⁺ transport, has been observed on the mitochondrial membrane, but it remains unclear whether mitochondrial OCT3 is involved in MPP⁺ accumulation in mitochondria.</p><p><strong>Results: </strong>OCT3 was detected in the mitochondria fraction of SH-SY5Y cells, located on both the inner membrane and outer membrane. Following MPP⁺ incubation, there was a significant increase in mitochondrial uptake of MPP⁺, which was mitigated by OCT3 inhibition. Knockdown of the translocase of inner mitochondrial membrane 22 (TIMM22), an important component of the mitochondrial protein import apparatus, successfully reduced OCT3 levels on mitochondria without impairing mitochondrial morphology or mitochondrial membrane potential. TIMM22 knockdown reduced mitochondrial MPP⁺ uptake, which in turn rescued MPP⁺-induced mitochondrial fragmentation, complex I inhibition, and mitochondrial membrane potential reduction. Furthermore, TIMM22 knockdown suppressed caspase-9 and caspase-3 activation and reversed the alterations of BAX and BCL-xL induced by mitochondrial MPP⁺ accumulation.</p><p><strong>Conclusions: </strong>Here we found that OCT3 on neuronal mitochondria serves as an effective MPP⁺ transporter, crucial for mitochondrial MPP⁺ uptake and MPP⁺-induced neurotoxicity. Furthermore, TIMM22 downregulation can selectively reduce mitochondrial OCT3 and reverse MPP⁺-induced mitochondrial dysfunction and neurotoxicity, highlighting TIMM22 and OCT3 as potential therapeutic targets for MPP⁺-associated neurodegeneration and diseases.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"214"},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636280","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":"NeXtMD: a new generation of machine learning and deep learning stacked hybrid framework for accurate identification of anti-inflammatory peptides.","authors":"Chengzhi Xie, Yijie Wei, Xinwei Luo, Huan Yang, Hongyan Lai, Fuying Dao, Juan Feng, Hao Lv","doi":"10.1186/s12915-025-02314-8","DOIUrl":"10.1186/s12915-025-02314-8","url":null,"abstract":"<p><strong>Background: </strong>Accurate identification of anti-inflammatory peptides (AIPs) is crucial for drug development and inflammatory disease treatment. However, the short length and limited informational content of peptide sequences make precise computational recognition particularly challenging. While various machine learning and deep learning approaches have been explored, their limitations in feature representation and model integration hinder the effective discovery of novel AIPs.</p><p><strong>Results: </strong>In this study, we present NeXtMD, a novel dual-module stacked framework that integrates both machine learning (ML) and deep learning (DL) components for accurate AIP identification. NeXtMD systematically extracts four functionally relevant sequence-derived descriptors-residue composition, inter-residue correlation, physicochemical properties, and sequence patterns-and utilizes a two-stage prediction strategy. The first stage generates preliminary predictions using four distinct encoding strategies and ML classifiers, while the second stage employs a multi-branch residual network (ResNeXt) to refine prediction outputs. Benchmark evaluations demonstrate that NeXtMD outperforms current state-of-the-art methods on multiple performance metrics. Moreover, NeXtMD maintains strong generalization capabilities when applied to unseen peptide sequences, showing its robustness and scalability.</p><p><strong>Conclusions: </strong>NeXtMD offers a high-performance and interpretable computational framework for AIP identification, with significant potential to facilitate the discovery and design of peptide-based anti-inflammatory therapeutics. The architecture and methodological innovations of NeXtMD also provide a generalizable strategy that can be adapted to other bioactive peptide prediction tasks, supporting broader applications in therapeutic peptide development.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"212"},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636279","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 minimized symbiotic gene set from the 1.68 Mb pSymB chromid of Sinorhizobium meliloti reveals auxiliary symbiotic loci.","authors":"Jason V S Kearsley, Barney A Geddes, George C diCenzo, Maryam Zamani, Turlough M Finan","doi":"10.1186/s12915-025-02298-5","DOIUrl":"10.1186/s12915-025-02298-5","url":null,"abstract":"<p><strong>Background: </strong>Symbiotic nitrogen-fixation between bacteria called rhizobia and leguminous plants is a critical aspect of sustainable agriculture. Complex, two-way communication governs the invasion of plant roots and the formation of nodules in which the rhizobia reduce N₂ to bioavailable ammonia. Research has uncovered many of the genes required for the symbiosis; however, engineering the symbiosis to function with alternative hosts such as cereal crops necessitates the establishment of a core set of symbiotic players.</p><p><strong>Results: </strong>We examined the symbiotic relevance of the genes on the 1.68 Mb pSymB chromid of the model rhizobium Sinorhizobium meliloti. By employing a strain in which pSymB was removed, we used a gain-of-function approach to assess a select group of known symbiotic regions totalling 261 kb (15.5%) of pSymB. This gene set enabled symbiotic N₂-fixation with alfalfa with a high degree of plant genotype-dependent variation in which nodules often senesced prematurely. We demonstrate that additional regions lacking canonical symbiosis genes are important for the efficient formation of symbiosis with the plant host. These regions appear to contain auxiliary symbiotic loci whose genes encode products with quasi-essential functions for the symbiosis and that are redundant in nature. We further established a 673-kb pSymB genome that engages consistently in N₂-fixation with alfalfa with 45% efficiency.</p><p><strong>Conclusions: </strong>The reduction of the pSymB genome showcases the complexity and nuance of its involvement in the N₂-fixing symbiosis.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"204"},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590516","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":"Ca²⁺-dependent vesicular and non-vesicular lipid transfer controls hypoosmotic plasma membrane expansion.","authors":"Baicong Mu, David M Rutkowski, Gianluca Grenci, Dimitrios Vavylonis, Dan Zhang","doi":"10.1186/s12915-025-02309-5","DOIUrl":"10.1186/s12915-025-02309-5","url":null,"abstract":"<p><strong>Background: </strong>Robust coordination of surface and volume changes is critical for cell integrity. Few studies have elucidated the plasma membrane (PM) remodeling events during drastic cell surface and volume alteration, especially regarding PM sensing and its subsequent rearrangements.</p><p><strong>Results: </strong>In this article, using fission yeast protoplasts, we reveal a Ca²⁺-dependent mechanism for membrane addition that ensures PM integrity and allows its expansion during acute hypoosmotic cell swelling. We show that MscS-like mechanosensitive channels activated by PM tension control extracellular Ca²⁺ influx, which triggers potential direct lipid transfer at endoplasmic reticulum (ER)-PM contact sites by conserved extended-synaptotagmins and accelerates exocytosis, enabling PM expansion necessary for osmotic equilibrium. Defects in any of these key events result in rapid protoplast rupture upon severe hypotonic shock. Our numerical simulations of such hypoosmotic PM expansion further propose a cellular strategy that combines instantaneous non-vesicular lipid transfer with bulk exocytic membrane delivery to maintain PM integrity for dramatic cell surface/volume adaptation.</p><p><strong>Conclusions: </strong>We propose a cellular strategy that combines instantaneous non-vesicular lipid transfer with bulk exocytic membrane delivery to maintain PM integrity for dramatic cell surface/volume adaptation.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"207"},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590528","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":"Fungus-mediated plant-pollinator mutualism in Monoon laui (Annonaceae): functional differentiation of stigmatic exudate and petal nectar.","authors":"Yanwen Chen, Bine Xue, Juan Diego Gaitán-Espitia, Richard M K Saunders","doi":"10.1186/s12915-025-02308-6","DOIUrl":"10.1186/s12915-025-02308-6","url":null,"abstract":"<p><strong>Background: </strong>Floral nectar typically functions as a pollinator reward in mutualistic flower-pollinator interactions, with this mutualism sometimes strengthened when plants provide the pollinators with brood sites and larval food as rewards. The functional and molecular mechanisms underpinning such rewards remain unclear.</p><p><strong>Results: </strong>We present strong circumstantial evidence supporting a fungus-mediated plant-pollinator mutualism in a beetle-pollinated early-divergent angiosperm, Monoon laui (Annonaceae), which has flowers that produce exudates on both the stigmas and inner petals, with fungi that develop on the inner petals subsequently consumed by insect larvae. The identities of the pollinators and larvae, as well as the fungal communities borne on the pollinators and petals, indicate that the pollinators disperse fungi while ovipositing on the petals. The nutritional value of the two exudates reveals that the stigmatic exudate is sugar-rich, whereas the inner petal exudate has a greater amino acid content. Transcriptomic and proteomic comparisons between the two organs and their exudates corroborate the nutritional profiles, with a stronger immune response on stigmas.</p><p><strong>Conclusions: </strong>Both stigmatic exudate and petal nectar of Monoon laui function as a pollinator reward, while petals with their nectar are moreover critical in the fungus-mediated plant-pollinator mutualism, as they are likely to be closely adapted to the requirements of the pollinators by providing them with brood sites and larval food, thereby increasing their population size during the flowering season and promoting pollination success.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"206"},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590529","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 reference genome enhances the power to detect signatures of recent anthropogenic impact in genomic data: a lesson learned from a stag beetle system.","authors":"Zong-Yu Shen, My-Hanh Le, Ming-Hsun Chou, Jen-Pan Huang","doi":"10.1186/s12915-025-02307-7","DOIUrl":"10.1186/s12915-025-02307-7","url":null,"abstract":"<p><strong>Background: </strong>Genomic data are vital for conservation biology and recent advances in sequencing technology have facilitated their applicability. However, the role of reference genomes in conservation planning remains largely underexplored. Specifically, while reference genomes can improve the accuracy of estimating genetic indices and help detect genomic regions under selection, they are still limited for non-model species. We explored whether a reference genome can help reveal novel insights not detected by previous genome-wide SNP analyses in a stag beetle system, especially in understanding recent demographic changes and local adaptation, which are critical information for conservation planning.</p><p><strong>Results: </strong>We used Oxford Nanopore Technology (ONT) to sequence and assemble a draft genome of an endemic stag beetle Lucanus miwai in Taiwan. With this newly generated genome map, we reanalyzed a previously published ddRADseq dataset. Our results revealed that the three geographical lineages of L. miwai exhibit varying levels of runs of homozygosity (ROH), with the lineage experiencing the most severe and recent habitat disturbance showing the longest ROH. Furthermore, the inferred timing and duration of a recent bottleneck coincide with historical records of recent habitat destruction. We also identified putative genomic regions showing signals of divergent selection between the lineages, indicating the importance of maintaining geographical lineages as separate conservation units.</p><p><strong>Conclusions: </strong>The impact of anthropogenic disturbance among different geographical lineages of L. miwai can be detected using genomic data only when a reference genome is available. Furthermore, a reference genome helps us identify a genomic region that may have experienced a recent selective sweep. Our findings thus provide empirical evidence supporting the crucial roles of reference genomes in conservation planning.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"205"},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590527","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 14-bp motif in the KIT active promoter region is critical for melanin accumulation in yaks, mice, and humans.","authors":"Xinfeng Liu, Tongcheng Wang, Zeyu Zheng, Congcong Dong, Wenyu Liu, Zhimin Niu, Yingbo Yang, Xiaoyun Wu, Qiang Qiu, Yongzhi Yang, Kexin Li, Johannes A Lenstra, Ping Yan, Minghui Kang, Bowen Li, Lingzhao Fang, Jianquan Liu","doi":"10.1186/s12915-025-02311-x","DOIUrl":"10.1186/s12915-025-02311-x","url":null,"abstract":"<p><strong>Background: </strong>Animal pigmentation serves as an excellent model for studying genetics, development, and evolution. Among yak breeds, the all-white yak breed (Bos grunniens) is the only indigenous variety with pristine white fur, in stark contrast to the black coat color of the wild yak and most domesticated yaks.</p><p><strong>Results: </strong>Using whole-genome sequencing data from 387 yaks, we analyzed the population genetic structure of all-white yaks and discovered that they clustered into two distinct genetic groups. Further, by conducting a genome-wide association study (GWAS) based on whole-genome variants (SNPs and indels) between all-white and wild-type yaks, we identified a 14-bp deletion in the promoter of KIT, which decreased its expression in all-white yaks. The following knock-in experiments in mouse confirmed that the absence of the yak 14-bp motif decreases the expression of KIT. Deletion of a human orthologue of the yak 14-bp motif by using the CRISPR/Cas9 system reduces the melanin accumulation in human melanoma cells.</p><p><strong>Conclusions: </strong>Overall, our study revealed the genetic basis of all-white yaks and underscored the importance of studying livestock phenotypes to uncover conserved genetic regulators in mammals.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"208"},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590515","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}