BMC Biology最新文献

{"title":"The genome of a sea spider corroborates a shared Hox cluster motif in arthropods with a reduced posterior tagma.","authors":"Nikolaos Papadopoulos, Siddharth S Kulkarni, Christian Baranyi, Bastian Fromm, Emily V W Setton, Prashant P Sharma, Andreas Wanninger, Georg Brenneis","doi":"10.1186/s12915-025-02276-x","DOIUrl":"10.1186/s12915-025-02276-x","url":null,"abstract":"<p><strong>Background: </strong>Chelicerate evolution is contentiously debated, with recent studies challenging traditional phylogenetic hypotheses and scenarios of major evolutionary events, like terrestrialization. Sea spiders (Pycnogonida) represent the uncontested marine sister group of all other chelicerates, featuring a-likely plesiomorphic-indirect development. Accordingly, pycnogonids hold the potential to provide crucial insight into the evolution of chelicerate genomes and body patterning. Due to the lack of high-quality genomic and transcriptomic resources, however, this potential remains largely unexplored.</p><p><strong>Results: </strong>We employ long-read sequencing and proximity ligation data to assemble the first near chromosome-level sea spider genome for Pycnogonum litorale, complemented by comprehensive transcriptomic resources. The assembly has a size of 471 Mb in 57 pseudochromosomes, a repeat content of 61.05%, 15,372 predicted protein-coding genes, and robust completeness scores (95.8% BUSCO Arthropoda score, 95.7% of conserved microRNA families). Genome-scale self-synteny and homeobox gene cluster analysis show no evidence of a whole-genome duplication (WGD). We identify a single, intact Hox cluster lacking Abdominal-A (abdA/Hox9), corroborated by the absence of an abdA ortholog in the novel transcriptomic resources.</p><p><strong>Conclusions: </strong>Our high-quality genomic and transcriptomic resources establish P. litorale as a key research organism for modern studies on chelicerate genome evolution, development, and phylogeny. The lack of WGD signature in P. litorale further strengthens the inference that WGDs are derived traits in the chelicerate tree. The combination of abdA loss with the reduction of the posterior tagma emerges as a common theme in arthropod evolution, as it is shared with other, distantly related arthropod taxa with a vestigial opisthosoma/abdomen.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"196"},"PeriodicalIF":4.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539062","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":"Development and characterization of a fully humanized ACE2 mouse model.","authors":"Chunyu Ge, Amr R Salem, Amany Elsharkawy, Janhavi Natekar, Anchala Guglani, Jaser Doja, Osarume Ogala, Gavin Wang, Susan H Griffin, Orazio J Slivano, Robin Shoemaker, Benard O Ogola, Christopher F Basler, Ajay Kumar, W Bart Bryant, Mukesh Kumar, Joseph M Miano","doi":"10.1186/s12915-025-02293-w","DOIUrl":"10.1186/s12915-025-02293-w","url":null,"abstract":"<p><strong>Background: </strong>Many humanized angiotensin-converting enzyme 2 (ACE2) mouse models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection do not replicate human ACE2 protein expression and thus exhibit pathology infrequently observed in humans. To address this limitation, we designed and characterized a fully humanized ACE2 (hACE2) mouse by replacing all exons/introns of the mouse Ace2 locus with human DNA comprising the entire ACE2 gene and an upstream long noncoding RNA (LncRNA).</p><p><strong>Results: </strong>Compared to the popular Keratin18 ACE2 (KRT18-ACE2, K18) mouse model of SARS-CoV-2 infection, hACE2 mice displayed a similar tissue expression profile of ACE2 as that seen in human tissues. Further, hACE2 mice showed comparable blood pressure, angiotensin II metabolism, and renal cortical transcriptome as wild-type mice. Intranasal infection of K18 mice with the beta variant of SARS-CoV-2 resulted in high viral replication and inflammation of the lung and brain, weight loss, and compassionate euthanasia five days post-infection (PI). Similarly infected hACE2 mice displayed viral replication and inflammation in the lung (but not in brain), sustained weight, and 100% survival up to 12 days PI, with clear evidence of acquired immunity. CRISPR-mediated disruption of the upstream LncRNA caused minimal effects on ACE2 mRNA and protein.</p><p><strong>Conclusions: </strong>The hACE2 model offers a more accurate approach to studying mechanisms underlying tissue-restricted expression of ACE2, elucidating noncoding sequence variants and an upstream LncRNA, and defining pathways relevant to human disease and associated co-morbidities.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"194"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539044","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":"Mutations of the complex I PSST target gene confers acaricide resistance and a fitness cost in Panonychus citri.","authors":"Deng Pan, Menghao Xia, Chuanzhen Li, Xunyan Liu, Lewis Archdeacon, Andrias O O'Reilly, Guorui Yuan, Jinjun Wang, Wei Dou","doi":"10.1186/s12915-025-02288-7","DOIUrl":"10.1186/s12915-025-02288-7","url":null,"abstract":"<p><strong>Background: </strong>Pesticide resistance is a serious problem that threatens crop industries. Major resistance towards pyridaben, an acaricidal inhibitor of mitochondrial electron transport complex I (METI-Is), has been reported in tetranychids following its extensive use worldwide. Understanding mechanisms of pyridaben resistance is crucial for sustainable resistance management.</p><p><strong>Results: </strong>The inheritance of pyridaben resistance was incompletely recessive and controlled by multiple genes in P. citri, which was determined by reciprocal crosses and backcross experiments. Bulked segregant analysis was performed to identify gene loci underlying pyridaben resistance. Subsequently, the two PSST-subunit mutations H107R and the previously undiscovered V103I mutation were positively correlated with pyridaben resistance in different populations or strains by single mite genotyping. The bioassay further showed that H107R contributed to moderate resistance, while V103I in combination with H107R was responsible for a very high level of resistance in homozygous P. citri strains. These contributions to pyridaben resistance were also verified in transgenic Drosophila through the introduction of the wildtype, single- or double-mutated P. citri PSST subunit. In addition, life-table analysis and behavioral measures were conducted to assess the fitness cost associated with resistance development. Accompanied by reduced ATP levels and complex I activity, a fitness cost was observed as reduced fecundity and lower mobility due to PSST mutations.</p><p><strong>Conclusions: </strong>Our findings provide direct evidence that PSST mutations conferred the evolution of pyridaben resistance but simultaneously led to a fitness cost due to functional defects in complex I. These data provide theoretical insights into sustainable resistance management in agricultural production.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"190"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538971","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":"AMCL: supervised contrastive learning with hard sample mining for multi-functional therapeutic peptide prediction.","authors":"Jiwei Fang, Henghui Fan, Jintao Zhao, Jianping Zhao, Junfeng Xia","doi":"10.1186/s12915-025-02273-0","DOIUrl":"10.1186/s12915-025-02273-0","url":null,"abstract":"<p><strong>Background: </strong>Multi-functional therapeutic peptides have emerged as promising candidates in drug development and disease diagnosis due to their biocompatibility, targeting capability, and low immunogenicity. However, the identification of peptide functions through wet-lab experiments is both time-consuming and costly, necessitating efficient computational prediction methods. The field faces challenges such as long-tail distribution problems, data sparsity, and complex label co-occurrence patterns due to peptides' multi-functional nature.</p><p><strong>Results: </strong>To address these challenges, we propose AMCL, a novel framework for multi-functional therapeutic peptide prediction. AMCL incorporates a semantic-preserving data augmentation strategy, a multi-label supervised contrastive learning mechanism with hard sample mining, and a weighted combined loss combining Focal Dice Loss (FDL) and Distribution-Balanced Loss (DBL) to alleviate class imbalance issues. Additionally, we introduce a category-adaptive threshold selection mechanism for individual functional categories. The interpretability of AMCL is demonstrated through feature space analysis and Gradient-weighted Class Activation Mapping (Grad-CAM) visualization.</p><p><strong>Conclusions: </strong>Comprehensive experiments show that AMCL significantly outperforms existing methods across multiple key metrics, including Absolute true, Accuracy, Macro-F1, and Micro-F1, establishing a new state-of-the-art in therapeutic peptide multi-functional prediction.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"170"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539024","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":"An ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in Europe.","authors":"Christian Urban, Bram Vrancken, Livia V Patrono, Ariane Düx, Mathilde Le Vu, Katarina L Matthes, Nina Maria Burkhard-Koren, Navena Widulin, Thomas Schnalke, Sabina Carraro, Frank Rühli, Philippe Lemey, Kaspar Staub, Sébastien Calvignac-Spencer, Verena J Schuenemann","doi":"10.1186/s12915-025-02282-z","DOIUrl":"10.1186/s12915-025-02282-z","url":null,"abstract":"<p><strong>Background: </strong>From 1918 to 1920, the largest influenza A virus (IAV) pandemic known to date spread globally causing between 20 to 100 million deaths. Historical records have captured critical aspects of the disease dynamics, such as the occurrence and severity of the pandemic waves. Yet, other important pieces of information such as the mutations that allowed the virus to adapt to its new host can only be obtained from IAV genomes. The analysis of specimens collected during the pandemic and still preserved in historical pathology collections can significantly contribute to a better understanding of its course. However, efficient RNA processing protocols are required to work with such specimens.</p><p><strong>Results: </strong>Here, we describe an alternative protocol for efficient ancient RNA sequencing and evaluate its performance on historical samples, including a published positive control. The phenol/chloroform-free protocol efficiently recovers ancient viral RNA, especially small fragments, and maintains information about RNA fragment directionality through incorporating fragments by a ligation-based approach. One of the assessed historical samples allowed for the recovery of the first 1918 IAV genome from Switzerland. This genome, derived from a patient deceased during the beginning of the first pandemic wave in Switzerland, already harbours mutations linked to human adaptation.</p><p><strong>Conclusion: </strong>We introduce an alternative, efficient workflow for ancient RNA recovery from formalin-fixed wet specimens. We also present the first precisely dated and complete influenza genome from Europe, highlighting the early occurrence of mutations associated with adaptation to humans during the first European wave of the 1918 pandemic.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"179"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539026","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":"Construction of the graph genomes of Takifugu provides novel insights into the genomic mechanisms of population structure and migratory traits.","authors":"Rui-Shi He, Rong Zhao, Jun-Jie Lin, Yan Li, Xiang-Zhu Kong, Jin-Xuan Xu, Jing-Hang Wu, Xing-Jiang Bu, Yong-Jun Zhang, Yang Sun","doi":"10.1186/s12915-025-02296-7","DOIUrl":"10.1186/s12915-025-02296-7","url":null,"abstract":"<p><strong>Background: </strong>The genus Takifugu includes highly valued fish species known for their delicate flavor, making them popular in multiple countries. However, many species from this genus face significant threats. In order to better understand the genetic diversity and evolutionary dynamics of Takifugu, a syntelog-based pan-genome and graph genome were constructed using the data of seven Takifugu species.</p><p><strong>Results: </strong>The analysis of 28,085 syntelog groups (SGs) composed of protein-coding genes revealed that only 57.3% of the SGs were shared among all individuals, whereas the remaining genes presented presence-absence variation (PAV) across the seven genomes. Using the graph genome as a reference, a population of 160 Takifugu individuals was analyzed, from which 20,133,471 SNPs, 4,606,141 Indels, and 152,200 SVs were identified. The gene flow analysis revealed directional gene flow from Takifugu bimaculatus and Takifugu flavidus to Takifugu oblongus. Notably, a 51-bp insertion in the ABCB9 gene differed significantly in frequency between the two migratory populations, suggesting the potential role of this gene in the migratory behavior of these species. Additionally, the expression profiles from 13 tissues or organs (brain, gallbladder, gill, gonad, heart, kidney, liver, muscle, pituitary, skin, spleen, stomach, and swim bladder) revealed a unique expression pattern in the liver, with the tissue-specific genes exhibiting evolutionary conservation to varying degrees. The highest proportion of core genes was found in the pituitary, whereas the lowest was found in the spleen.</p><p><strong>Conclusions: </strong>This study provides comprehensive genomic resources that enhance the understanding of the genetic diversity and evolutionary dynamics of Takifugu species. The findings offer insights for research on both breeding and conservation of Takifugu.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"195"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539041","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":"Joint fusion of sequences and structures of drugs and targets for identifying targets based on intra and inter cross-attention mechanisms.","authors":"Xin Zeng, Guang-Peng Su, Wen-Feng Du, Bei Jiang, Yi Li, Zi-Zhong Yang","doi":"10.1186/s12915-025-02256-1","DOIUrl":"10.1186/s12915-025-02256-1","url":null,"abstract":"<p><strong>Background: </strong>Accurately identifying targets not only guides treatments for diseases with unclear pathogenic mechanisms, but also reduces pharmaceutical costs and accelerates drug development timelines. However, the primary challenge in targets identification currently lies in the low accuracy of existing computational methods.</p><p><strong>Results: </strong>We propose MM-IDTarget, a novel deep learning framework that employ a multimodal fusion strategy based on the intra and inter cross-attention mechanisms. MM-IDTarget integrates some cutting-edge deep learning techniques such as graph transformer, multi-scale convolutional neural networks (MCNN), and residual edge-weighted graph convolutional network (EW-GCN) to extract sequence and structure modal features of drugs and targets. This framework enhances the complementary of multimodal features by employing the intra and inter cross-attention mechanisms, facilitating effective fusion of multimodal features within drug and target and between drug and target. Furthermore, MM-IDTarget incorporates the physicochemical features of drug and target, utilizing fully connected networks to predict drug-target interactions (DTI).</p><p><strong>Conclusions: </strong>Experimental results show that despite our benchmark dataset being one-third or the same size of those used by current state-of-the-art methods, MM-IDTarget achieves the performance on par with or superior to these methods across most Top-K evaluation metrics based on the same test set for targets identification. Moreover, MM-IDTarget exhibits the strong application capability on two generalization datasets and one dataset constructed from approved drugs, establishing it as a robust tool for targets identification.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"168"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538966","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":"Biomonitoring 2.0 Refined: observing local change through metaphylogeography using a community-based eDNA metabarcoding monitoring network.","authors":"Andrew C Riley, Michael Wright, Teresita M Porter, V Carley Maitland, Donald J Baird, Mehrdad Hajibabaei","doi":"10.1186/s12915-025-02284-x","DOIUrl":"10.1186/s12915-025-02284-x","url":null,"abstract":"<p><strong>Background: </strong>Biological data at different levels of organization is essential to support actions to mitigate the current biodiversity crisis. DNA metabarcoding is an established method to detect species/genus level taxa from bulk samples leading the way for a Biomonitoring 2.0 framework. Biomonitoring 2.0 Refined adds another dimension to Biomonitoring 2.0-high-throughput, scalable DNA metabarcoding with a higher resolution at the intraspecific level. Intraspecific diversity is key to understanding the distribution and movement of local populations for conservation efforts. Gaining reliable intraspecific information from metabarcoding data, however, is challenging due to qualitative/quantitative issues that can impact validity of the inference.</p><p><strong>Results: </strong>Samples collected for the STREAM community-based monitoring project were used to perform an intraspecific genetic variation analysis on benthic arthropods. We targeted two non-overlapping cytochrome c oxidase subunit 1 mitochondrial DNA amplicons to assess the reproducibility of our results. Samples from the Rocky Mountains were grouped into four regions separated by mountain ranges. Significant separation (PERMANOVA, p value < 0.05) of Sørensen dissimilarity between regions was observed for community and intraspecific levels, fitting the expectation that mountains are barriers to dispersal. Two of the regions showed significant spatial structuring (Mantel test, p value < 0.05) at the intraspecific level, while all regions showed significant structuring at the community level. Results were consistent across both amplicons.</p><p><strong>Conclusions: </strong>We show that DNA metabarcoding is applicable to intraspecific diversity analysis and it is robust to different amplicons. This paves the way for Biomonitoring 2.0 Refined, which can provide much needed fine-scale biodiversity data for ecological assessments and conservation.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"187"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539039","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":"Multi-omics profiling of Nanhaia speciosa and Nanhaia fordii: insights into lectin dynamics, nodulation, and triterpenoid saponin biosynthesis.","authors":"Zhiying Li, Jiabin Wang, Junfang Zhang, Yunliu Fu, Yonglin Jing, Bilan Huang, Huazhou Wu, Chunyang Meng, Li Xu","doi":"10.1186/s12915-025-02278-9","DOIUrl":"10.1186/s12915-025-02278-9","url":null,"abstract":"<p><strong>Background: </strong>Nanhaia speciosa (N. speciosa) has long been served as a traditional medicinal and edible plant. N. speciosa and Nanhaia fordii (N. fordii) are the only two species under the Nanhaia genus, but the latter is of limited use. As a closely related species, N. fordii has a highly similar appearance and taste to N. speciosa and was used in the market to impersonate N. speciosa with potential harm to health.</p><p><strong>Results: </strong>To analyze the differences and underlying basis between N. speciosa and N. fordii, we conducted a comprehensive comparison of their genomic, transcriptomic, and metabolomic data. Using PacBio HiFi and Hi-C data, we achieved high-quality haploid genomes for both N. speciosa and N. fordii. Comparative analysis reveals the elevated expression of Wisteria lectin-like genes in N. fordii, corresponding with higher heat-resistance lectin content in N. fordii than in N. speciosa, potentially causing food poisoning due to increased lectin levels in the plant. Metabolomic analysis indicates that licorice saponins are the main components contributing to the sweetness in N. fordii and N. speciosa, making it the only reported plant, apart from the licorice genus, containing licorice saponins. Moreover, the nodulation key gene RPG cannot be expressed in the roots of N. speciosa, possibly explaining the ability of N. fordii to form nodules while N. speciosa cannot.</p><p><strong>Conclusions: </strong>Leveraging high-quality haploid genome assembly and multi-omics analysis, our data provides a crucial foundation for identifying key metabolic components and candidate genes associated with important traits and for breeding new varieties of N. fordii and N. speciosa.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"169"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538970","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":"doc2a and doc2b contribute to locomotor and social behaviors by down-regulating npas4b in zebrafish.","authors":"Yali Chi, Tao Feng, Zixin Du, Ping Huang, Wenjun Yu, Haihua Liu, Wanshan Wang, Xinping Yang, Liping Huang","doi":"10.1186/s12915-025-02224-9","DOIUrl":"10.1186/s12915-025-02224-9","url":null,"abstract":"<p><strong>Background: </strong>Copy number variations (CNVs) occurring on chromosome 16p11.2 are associated with various neurodevelopmental disorders, including autism spectrum disorder (ASD), schizophrenia, and intellectual disability. Among the genes situated within the critical CNV region, DOC2A is noteworthy. We generated frameshift mutations in doc2a (double C2-like domain-containing protein a) and its paralog doc2b (double C2-like domain-containing protein b) in zebrafish via CRISPR-Cas9 respectively and obtained double-mutant doc2a^-/-doc2b^-/- by mating the single-mutant doc2a^+/+doc2b^-/- and doc2a^-/-doc2b^+/+ zebrafish.</p><p><strong>Results: </strong>doc2a^-/-doc2b^-/- mutants displayed aberrant morphology including tail bending and deformity, and morphologically normal individuals displayed aberrant behaviors, including reduced locomotion activity, impaired social interaction, and irregular movements. Whole-brain transcriptome sequencing of both wild-type and doc2a^-/-doc2b^-/- mutants revealed differentially expressed genes (DEGs) enriched with ASD candidate genes and synaptic signaling pathways, notably down-regulated gene npas4b (Neuronal PAS domain protein 4b). We found the downstream targets of the transcription factor Npas4b in the DEGs were mostly enriched in the synaptic signaling pathways. The npas4b knockout and knockdown zebrafish showed reduced locomotion activity and impaired social interaction similar to the behaviors observed in doc2a^-/-doc2b^-/- mutants.</p><p><strong>Conclusions: </strong>This study suggests that DOC2A in the critical region of 16p11.2 may contribute to the pathogenesis of autism by interacting with other genes, such as DOC2B, and that the downregulation of NPAS4 may play an important role in autism.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"167"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539045","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}