GenomicsPub Date : 2025-08-08DOI: 10.1016/j.ygeno.2025.111094
Junna Liu , Jian Liu , Ping Zhang , Qianchao Wang , Li Li , Hanxue Li , Shunhe Cheng , Peng Qin
{"title":"Transcriptomic and metabolomic profilings reveal the mechanism of related metabolites and gene regulatory networks of quinoa leaves to Spodoptera exigua feeding during flowering periods","authors":"Junna Liu , Jian Liu , Ping Zhang , Qianchao Wang , Li Li , Hanxue Li , Shunhe Cheng , Peng Qin","doi":"10.1016/j.ygeno.2025.111094","DOIUrl":"10.1016/j.ygeno.2025.111094","url":null,"abstract":"<div><div>The transcriptional response of plants to insect attacks involves dynamic signaling and synthetic reprogramming, which change over time. To elucidate the defensive response of quinoa to feeding by <em>S. exigua</em>, quinoa leaves were fed on by <em>S.exigua</em> for 5, 15, 30 and 60 min, and the transcriptomes and metabolomes were compared with those of uneaten control. When <em>S.exigua</em> fed on quinoa leaves for 15 min, the expression of <em>CqMYB44L1</em> and <em>CqMYB44L2</em> underwent stronger and faster changes, closely related to jasmonic acid. The quercetin content gradually increased with longer feeding durations, JA content was lowest at 15 min. DEGs were associated with plant hormone signal transduction and alpha-linolenic acid metabolism, which are related to quinoa resistance to <em>S.exigua</em>. Subcellular localization indicates <em>CqMYB44L1</em> and <em>CqMYB44L2</em> located in the nucleus and had transcriptional activity. Overexpression of <em>CqMYB44L1</em> and <em>CqMYB44L2</em> increased JA content in <em>Arabidopsis</em> leaves, and resulted in JA-mediated resistance to <em>S.exigua</em> feeding.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111094"},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2025-08-05DOI: 10.1016/j.ygeno.2025.111093
Qiushuang Han , Yingying Xia , Yang Zhao, Yi Li, Jing Xu, Yuting Luo, Yuanyuan Wang, Jun Zhang
{"title":"Integrated analysis of transcriptomics and proteomics hinted that PI3k-Akt and TGF-beta signaling pathways may synergistically regulate calipash development of Chinese Soft-Shell turtle at embryonic stage","authors":"Qiushuang Han , Yingying Xia , Yang Zhao, Yi Li, Jing Xu, Yuting Luo, Yuanyuan Wang, Jun Zhang","doi":"10.1016/j.ygeno.2025.111093","DOIUrl":"10.1016/j.ygeno.2025.111093","url":null,"abstract":"<div><div>Calipash is a special connective tissue on the carapace posterior margin of Chinese Soft-Shell turtle (<em>Pelodiscus sinensis</em>), which is closely related to the stress resistance and nutritional value deposition of <em>P. sinensis</em>. However, previous studies lack knowledge about calipash development, thus its developmental regulation mechanisms are still unclear. In this study, transcriptomics and proteomics analysis of calipash at TK17-TK19 embryonic stages of <em>P. sinensis</em> were used to explore the mechanisms that regulate calipash development. Function analysis of DEGs and DEPs revealed that PI3K-Akt and TGF-beta signaling pathways were significantly related to calipash development. The gene knockdown experiments further validated the regulatory mechanisms of two pathways in calipash development. Results revealed that the PI3K-Akt and TGF-beta signaling pathways jointly participate in regulating the proliferation of calipash cells and the type I collagen anabolism. Our results provided novel insights for understanding of the developmental regulation mechanism of the <em>P. sinensis</em> calipash tissue.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111093"},"PeriodicalIF":3.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2025-07-31DOI: 10.1016/j.ygeno.2025.111092
Chaoqi Wang , Ta QuangKiet , Wenqing Li , Banghong Jian , Xiping Yang
{"title":"Integration of transcriptome and metabolome reveals candidate metabolites responding to drought stress in sugarcane","authors":"Chaoqi Wang , Ta QuangKiet , Wenqing Li , Banghong Jian , Xiping Yang","doi":"10.1016/j.ygeno.2025.111092","DOIUrl":"10.1016/j.ygeno.2025.111092","url":null,"abstract":"<div><div>Drought stress severely restricts sugarcane (<em>Saccharum</em> spp. cultivars) productivity, a globally vital sugar crop, yet the metabolic basis of its drought resistance remains elusive. Here, we integrated transcriptomic and metabolomic profiles of drought-stressed sugarcane to decipher the regulatory mechanisms. Using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS), we identified 157 differentially expressed genes (DEGs) and 18 differentially accumulated metabolites (DAMs) specifically induced under drought stress. These DEGs/DAMs were co-enriched in 2-oxocarboxylic acid metabolism and branched-chain amino acid (valine/leucine/isoleucine) degradation pathways. Through weighted gene co-expression network analysis (WGCNA), we pinpointed three hub metabolites, tryptophan, proline, and 6-methylquinoline (6-MQ), exhibit a significant correlation with DEGs. Functional validation demonstrated that exogenous 6-MQ application significantly enhanced drought tolerance in sugarcane (17.6 % lower mortality) without growth penalty. Our study not only unravels a novel 6-MQ-mediated regulatory module but also provides valuable metabolite resources for improving drought resistance in sugarcane breeding.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111092"},"PeriodicalIF":3.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2025-07-26DOI: 10.1016/j.ygeno.2025.111091
Yufei Zhang , Huifen Cao , Fujian Yang , Chunlian Wang , Guihua Wang , Binghui Wang , Dingcai Lai , Mengling Fang , Zhengmian Zhang , Yong Diao , Dianliang Lin , Tenghui Zhan , Philipp Kapranov
{"title":"High-resolution genome-wide profiling reveals intricate relationship between DNA damage and sperm physiology","authors":"Yufei Zhang , Huifen Cao , Fujian Yang , Chunlian Wang , Guihua Wang , Binghui Wang , Dingcai Lai , Mengling Fang , Zhengmian Zhang , Yong Diao , Dianliang Lin , Tenghui Zhan , Philipp Kapranov","doi":"10.1016/j.ygeno.2025.111091","DOIUrl":"10.1016/j.ygeno.2025.111091","url":null,"abstract":"<div><div>Little is known about genome-wide profiles of different types of DNA damage in spermatozoa and how they relate to sperm quality. In this study, we for the first time constructed and analyzed high-resolution profiles of two very common DNA lesions in normal human sperm. We found non-random genomic distributions of the DNA lesions and a very complex relationship between DNA damage and sperm quality that depends on the type of DNA lesion and genomic location. We connected intricate details of genomic patterns of DNA damage with physiological properties of cells. We found an intriguing relationship between single-nucleotide hotspots of DNA damage and naturally occurring sequence variants, suggesting that certain regions of the genome are more prone to DNA damage which can lead to heritable sequence change. These results highlight complex relationship between DNA damage and cellular physiology which calls for more exploration of high-resolution genome-wide patterns of various DNA lesions.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111091"},"PeriodicalIF":3.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2025-07-21DOI: 10.1016/j.ygeno.2025.111090
Wei Huang , Yuzhu Sha , Xiu Liu , Yanyu He , Xiaowei Chen , Wenxin Yang , Qianling Chen , Min Gao , Jiqing Wang , Lei Wang , Bin Ma
{"title":"Temporal and spatial variation of fermentation function, microbiota characteristics and expression of VFAs transporter genes in the ruminant stomach of Tibetan sheep during different phenological phase","authors":"Wei Huang , Yuzhu Sha , Xiu Liu , Yanyu He , Xiaowei Chen , Wenxin Yang , Qianling Chen , Min Gao , Jiqing Wang , Lei Wang , Bin Ma","doi":"10.1016/j.ygeno.2025.111090","DOIUrl":"10.1016/j.ygeno.2025.111090","url":null,"abstract":"<div><div>The gut microbiota in Tibetan sheep's ruminant stomach varies across phenological phases, influencing nutrient absorption and adaptation. During the green grass period, acetic, propionic, and butyric acid concentrations in the rumen were higher than in the regreening and withered grass periods (<em>P</em> < 0.05). <em>MCT1</em> expression peaked during regreening. Bacteroidetes dominated during the withered grass period (<em>P</em> < 0.01), with <em>Rikenellaceae_RC9_gut_group</em> and <em>Prevotella</em> most abundant in the rumen. Spatially, rumen VFA concentrations and <em>MCT1</em> expression were significantly higher than in other stomachs (<em>P</em> < 0.05). Bacteroidetes, <em>Prevotella</em> and <em>Rikenellaceae_RC9_gut_group</em> were dominant across the ruminant stomach. Correlations between microbiota, VFAs, and transport genes highlight the interplay of fermentation, flora, and gene expression, crucial for Tibetan sheep's adaptation to the plateau environment.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111090"},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2025-07-18DOI: 10.1016/j.ygeno.2025.111089
Huabing Zhao , Zhaoying Han , Shulin Liu , Xiaoye Qi , Hongyan Li , Shaojing Wang
{"title":"A proposed Lawsonella species with distinct functional features from L. clevelandensis revealed by metagenomics","authors":"Huabing Zhao , Zhaoying Han , Shulin Liu , Xiaoye Qi , Hongyan Li , Shaojing Wang","doi":"10.1016/j.ygeno.2025.111089","DOIUrl":"10.1016/j.ygeno.2025.111089","url":null,"abstract":"<div><div>The skin serves as a vital barrier, largely influenced by the commensal microbiota. <em>Lawsonella clevelandensis</em>, the currently recognized sole species in the genus <em>Lawsonella</em>, has gained increased attention as a cause of abscesses but is often overlooked due to its fastidious nature, which make its isolation and culture in the lab particularly challenging. Here, a comprehensive genomic investigation of <em>Lawsonella</em> was conducted using a cultivation-free metagenomic approach, focusing on 39 newly generated and 12 publicly available genomes. A novel species represented by 43 metagenome-assembled genomes (MAGs) was proposed based on mono-clade formation, 16S rDNA sequence similarity and genome-wide average nucleotide identity (ANI) values. All these MAGs were initially identified as L. <em>clevelandensis</em> A by GTDB-tk. Here, we designed them as ‘<em>Candidatus</em> Lawsonella tjsk’ sp. nov.. Distinct genomic characteristics between this newly proposed species and L. <em>clevelandensis</em> were observed. Significant fundamental functional differences between the two species were revealed by species-specific genes.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111089"},"PeriodicalIF":3.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2025-07-17DOI: 10.1016/j.ygeno.2025.111086
Wendian Gong , Wenqi Ding , Tugeqin Bou , Lin Shi , Yanan Lin , Xiaoyuan Shi , Huize Wu , Zheng Li , Manglai Dugarjaviin , Dongyi Bai
{"title":"Ferulic acid mediates Mongolian horse skeletal muscle fiber remodeling through PDK1","authors":"Wendian Gong , Wenqi Ding , Tugeqin Bou , Lin Shi , Yanan Lin , Xiaoyuan Shi , Huize Wu , Zheng Li , Manglai Dugarjaviin , Dongyi Bai","doi":"10.1016/j.ygeno.2025.111086","DOIUrl":"10.1016/j.ygeno.2025.111086","url":null,"abstract":"<div><div>Ferulic acid (FA), a natural antioxidant and major active component in Angelica sinensis, has beneficial effects on skeletal muscle health; however, its role in modulating muscle fiber type composition Mongolian horse remains unclear. In this study, we found that FA promotes the proliferation of Mongolian horse skeletal muscle satellite cell (MuSCs), upregulates the expression of fast-twitch muscle marker genes (e.g., <em>MYH2</em>), and downregulates the expression of slow-twitch markers (e.g., <em>MYH7</em>). RNA-seq revealed that FA activates the HIF-1 signaling pathway, significantly increasing <em>PDK1</em> expression. Molecular docking analysis demonstrated that FA directly binds to <em>PDK1</em>, thereby facilitating the switch from slow- to fast-twitch muscle fibers. Functional assays using PDK1 knockdown and overexpression confirmed its regulatory role in muscle fiber type specification. Furthermore, RNA-seq and protein–protein interaction (PPI) network analyses indicated that PDK1 interacts with LDHA and IL6 to influence glycolysis and muscle contraction-related pathways. A feeding experiment further validated that FA promotes the transition toward fast-twitch muscle fibers in vivo. Collectively, our findings uncover a novel mechanism by which FA regulates muscle fiber type transformation through the HIF-1/PDK1 signaling axis.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111086"},"PeriodicalIF":3.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2025-07-17DOI: 10.1016/j.ygeno.2025.111087
Minyan Zhu , Yaping Yang , Hongjie Fang , Rong Chen
{"title":"Exploring the mechanism of action of trastuzumab-induced cardiomyocyte atrophy based on the FN1/PI3K/AKT-mediated mTOR-independent signaling pathway","authors":"Minyan Zhu , Yaping Yang , Hongjie Fang , Rong Chen","doi":"10.1016/j.ygeno.2025.111087","DOIUrl":"10.1016/j.ygeno.2025.111087","url":null,"abstract":"<div><div>Trastuzumab (TRZ) is a standard drug for the treatment of HER-2-positive breast cancer, but its cardiotoxicity seriously affects the prognosis of patients, and the potential mechanism of TRZ-induced cardiomyocyte atrophy leading to cardiotoxicity remains unclear. This study aimed to investigate the potential targets and signaling pathways of TRZ-induced cardiotoxicity using single-cell transcriptome sequencing (scRNA-seq) and bioinformatics methods. A total of 618 differentially expressed genes (DEGs) were identified through scRNA-seq and bioinformatics analysis. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Reactome analysis, Wiki pathway analysis, Protein-Protein Interaction (PPI) network analysis, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) results indicated that immune cell-derived FN1 may play a pivotal role in TRZ-induced cardiotoxicity by activating PI3K/AKT-mediated mTOR-independent signaling pathways in cardiomyocytes through extracellular matrix (ECM) mechanisms. Western blot analysis revealed that the expression of FN1, p-PI3K/PI3K, and p-AKT/AKT proteins was elevated in the TRZ group, no elevation of p-mTOR/mTOR and the autophagy level of cardiomyocytes was elevated, as well as the levels of myocardial atrophy and apoptosis were enhanced after treatment with TRZ. TEM revealed increased autolysosomes in TRZ-treated samples, while immunofluorescence analysis demonstrated exacerbated myocardial injury and significant cardiomyocyte atrophy in the TRZ group compared to CON. Our results demonstrate that TRZ-primed immune cells release FN1 which, through ECM triggers non-canonical (mTOR-independent) PI3K/AKT signaling in cardiomyocytes. This aberrant pathway drives excessive autophagy, initiating a pathological cascade from cellular atrophy to apoptotic death and ultimately manifesting as clinical cardiotoxicity.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111087"},"PeriodicalIF":3.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2025-07-17DOI: 10.1016/j.ygeno.2025.111088
Chuan Meng, Xiaodong Liu, Fang Wu, Xiaochao Ma, Lei Ma, Qingfeng Wang, Mingqiu Wang
{"title":"DNA methylation, metabolome, and transcriptome analysis reveal epigenomic differences between diploid Chinese cabbage seeds and tetraploid Chinese cabbage seeds","authors":"Chuan Meng, Xiaodong Liu, Fang Wu, Xiaochao Ma, Lei Ma, Qingfeng Wang, Mingqiu Wang","doi":"10.1016/j.ygeno.2025.111088","DOIUrl":"10.1016/j.ygeno.2025.111088","url":null,"abstract":"<div><div>This study aimed to elucidate the epigenomic differences between diploid and tetraploid Chinese cabbage seeds and preliminarily explore the mechanisms underlying the reduced seed vigor in tetraploid seeds. We comprehensively analyzed the transcriptome, metabolome, and whole-genome bisulfite sequencing (WGBS) to investigate gene expression, metabolite profiles, and DNA methylation patterns in diploid and tetraploid Chinese cabbage seeds from different years.</div><div>Results showed that tetraploid seeds exhibited lower DNA methylation levels and fewer methylated cytosines than diploid seeds across all sequence contexts (CG, CHG, and CHH). Differentially methylated regions (DMRs) were predominantly enriched in upstream and downstream regions of genes, with a higher number of hypermethylated regions in diploid seeds. Transcriptomic analysis revealed significant changes in gene expression before and after germination, with more genes downregulated post-germination. KEGG enrichment analysis indicated that differentially expressed genes were mainly involved in carbohydrate metabolism, amino acid metabolism, and signal transduction pathways. Metabolome analysis identified 1346 metabolites, with flavonoids and plant hormone signal transduction pathways being the most prominent. Notably, ABA-related genes, including seven ABF genes, 18 PYR/PYL genes, six SRK genes, and two PP2C genes, exhibited differential methylation and expression patterns between diploid and tetraploid seeds. These genes were enriched in pathways related to secondary metabolite biosynthesis and plant hormone signaling, suggesting a potential role in the reduced seed vigor of tetraploid seeds. In conclusion, our study provides a comprehensive understanding of the epigenetic and transcriptional characteristics underlying the differences in seed vigor between diploid and tetraploid Chinese cabbage seeds. The findings highlight the importance of DNA methylation and ABA signaling in regulating seed development and vigor.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111088"},"PeriodicalIF":3.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2025-07-12DOI: 10.1016/j.ygeno.2025.111079
Wangshan Zheng , Yiming Wang , Ying Li , Caijuan Bai , Yanan Yang , Yongbo Guo , Ouzhuluobu , Chaoying Cui , Xuebin Qi
{"title":"Genetic adaptations of innate immune genes in Tibetans: Insights into protection against pulmonary hypertension and hepatitis B virus infection in high-altitude environments","authors":"Wangshan Zheng , Yiming Wang , Ying Li , Caijuan Bai , Yanan Yang , Yongbo Guo , Ouzhuluobu , Chaoying Cui , Xuebin Qi","doi":"10.1016/j.ygeno.2025.111079","DOIUrl":"10.1016/j.ygeno.2025.111079","url":null,"abstract":"<div><div>The global dispersal of modern humans has driven genetic adaptations to diverse local environments, including high-altitude hypoxia and tropical rainforests, which represent some of the most extreme conditions. Different local environments exert distinct selective pressures on innate immunity. Here, we conducted a systematic analysis of innate immune gene variations and their evolutionary patterns in high-altitude populations using large-scale genomic data. The result posed that Tibetans harbored 26 Darwinian-positive selection genes, and they may confer protection against pulmonary hypertension by reducing infiltration and inflammatory responses and preventing cardiac hypertrophy. In particularly, we discovered four genes, <em>OAS3</em>, <em>IRAK4</em>, <em>RAB11A</em>, and <em>PLK1</em> with strong signals of positive selection. These genes are hypothesized to contribute to resistance against hepatitis B infection and the development of tolerance in Tibetans. Overall, the Tibetan population, facing the high-altitude hypoxic environment, has evolved a set of immune genes that combat hypoxia-induced inflammation and the hepatitis B virus infection.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111079"},"PeriodicalIF":3.4,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}