Gene最新文献

{"title":"Synergistic toxicity of compound heterozygous mutations in the COL4A3 gene causes end-stage renal disease in A large family of Alport syndrome.","authors":"Longxin Xie, Yuxi Ding, Ying Qiu, Yi Shi","doi":"10.1016/j.gene.2024.149132","DOIUrl":"10.1016/j.gene.2024.149132","url":null,"abstract":"<p><p>Alport syndrome (AS) is a genetic disorder characterized by kidney disease and hearing/vision abnormalities, resulting from mutations in the COL4A3, COL4A4, or COL4A5 genes. While numerous mutations have been identified in AS cases, the precise molecular mechanisms, particularly for compound mutations, remain under investigation. This study investigated the molecular mechanisms of AS in a proband with end-stage kidney disease (ESKD) using whole exome sequencing, which identified two compound heterozygous COL4A3 missense mutations: NM_000091.5:c.1354G > A (p.G452R) and NM_000091.5:c.4793 T > G (p.L1598R). Sixteen family members of the proband were genotyped, and further analyses, including in silico structural prediction, molecular docking, and in vitro co-immunoprecipitation assays, revealed that the p.G452R mutation disrupted the collagen triple helical structure, associated with hematuria in carriers, while the p.L1598R mutation interfered with the interaction between the NC1 domains of COL4A3 and COL4A4 proteins, crucial for collagen trimerization. These findings demonstrate a synergistic loss-of-function effect of the two mutations, contributing to the AS pathogenesis in the proband, and emphasize the importance of genetic screening and personalized treatment strategies for AS.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149132"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-34a-5p regulates agouti-related peptide via krüppel-like factor 4 and is disrupted by bisphenol A in hypothalamic neurons.","authors":"Minyi Yu, Wenyuan He, Denise D Belsham","doi":"10.1016/j.gene.2024.149129","DOIUrl":"10.1016/j.gene.2024.149129","url":null,"abstract":"<p><p>Obesity is a complex disease marked by increased adiposity and impaired metabolic function. While diet and lifestyle are primary causes, endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), significantly contribute to obesity. BPA, found in plastic consumer products, accumulates in the hypothalamus and dysregulates energy homeostasis by disrupting the neuropeptide Y (NPY)/agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) neurons. However, the precise molecular mechanisms of how BPA disrupts neuropeptide expression remains unclear. We hypothesized that microRNAs (miRNAs), which regulate approximately 60% of the human protein-coding genome and are crucial for hypothalamic energy regulation, may mediate the effects of BPA on Agrp. Using the TargetScanMouse 8.0 and DIANA microT bioinformatics tools, we identified miR-501-5p as a potential miRNA that directly regulates Agrp and the miR-34 family as miRNAs that indirectly regulate Agrp through its transcription factor krüppel-like factor 4 (KLF4). We found that in an immortalized NPY/AgRP-expressing cell line, mHypoE-41, miR-501-5p unexpectedly upregulated Agrp, while miR-34a-5p reduced Klf4 and Agrp mRNA levels. Serum starvation reduced miR-34a-5p levels and elevated Agrp mRNA levels, suggesting a potential role in AgRP regulation. Inhibiting the miR-34a-5p interaction with the Klf4 3'UTR using a specific target site blocker prevented the downregulation of both Klf4 and Agrp, suggesting miR-34a-5p alters Agrp mRNA levels via regulation of KLF4. BPA treatment increased Agrp and Klf4 expression while simultaneously decreasing miR-34a-5p levels, indicating miR-34a-5p may play a role in BPA-mediated dysregulation of Agrp. Overall, this study highlights indirect miRNA-based regulation of Agrp, which can also be dysregulated by obesogens, such as BPA.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149129"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Xhosa specific solute carrier family 22-member 2 haplotypes on the cellular uptake of metformin and cimetidine.","authors":"Zainonesa Abrahams-October, Yunus Kippie, Keenau Pearce, Rabia Johnson, Mongi Benjeddou","doi":"10.1016/j.gene.2024.149157","DOIUrl":"10.1016/j.gene.2024.149157","url":null,"abstract":"<p><strong>Background: </strong>Studies have shown that solute carrier transporters play an important role in the transport and distribution of metformin, and that genetic variation(s) in solute carrier genes have play a role in the variation of metformin efficacy and disposition observed in populations. This study aimed to determine the cellular uptake efficiency of metformin in SLC22A2 coding haplotypes of an indigenous South African population.</p><p><strong>Methods and results: </strong>To determine metformin and cimetidine cellular uptake in transfected HEK-293 cells, ultra high-performance liquid chromatography was used to quantitate substrate concentration(s). Haplotypes 3 and 4 showed decreased metformin uptake, and haplotypes 2 and 5 displayed increased metformin uptake in comparison to haplotype 1 (i.e. wildtype haplotype). Haplotypes 2-5 showed decreased uptake of cimetidine in comparison to haplotype 1, implying a reduced sensitivity to the inhibition of cimetidine. In all haplotypes, no significant transport was observed for metformin and cimetidine. Passive permeability of metformin was favoured in haplotypes 3 and 5, whilst the remaining haplotypes demonstrate higher passive permeability ratios in favour of cimetidine.</p><p><strong>Conclusion: </strong>Haplotype 4, which is characterised by the non-synonymous single nucleotide polymorphisms rs316019 and rs8177517, demonstrates potential impaired metformin transport.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149157"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cis-eQTL analysis reveals genes involved in biological processes of the immune system in Nelore cattle.","authors":"Thaís Cristina Ferreira Dos Santos, Evandro Neves Silva, Gabriela Bonfá Frezarim, Bruna Maria Salatta, Fernando Baldi, Larissa Fernanda Simielli Fonseca, Lucia Galvão De Albuquerque, Maria Malane Magalhães Muniz, Danielly Beraldo Dos Santos Silva","doi":"10.1016/j.gene.2024.149138","DOIUrl":"10.1016/j.gene.2024.149138","url":null,"abstract":"<p><p>The combination of transcriptional profiling and genotype data analyses enables the identification of genetic variants that may affect gene expression (eQTL - expression quantitative trait loci). This study aimed to identify cis-eQTL in Nellore cattle muscle tissue and determine their biological processes related to the immune system and involved eGenes. Genotypic data (SNP-Chip) and gene expression data (RNA-Seq) from a commercial population of 80 Nellore animals were evaluated. For the cis-eQTL identification, association tests were conducted for all variants near the gene (cis variants), followed by permutation tests to correct for multiple comparisons. Our analyses revealed 828 top cis-eQTL related to 1,062 genes of which most of these variants were in intronic and intergenic regions. The eQTLs rs109525554, rs109589165, rs110192253, rs133127698, rs137742430, rs41803313, rs43366333, and rs43711242 were associated with susceptibility and resistance to infections in cattle. Additionally, interferon family eGenes, such as IFNT3, IFN-TAU, IFNK, FYN, and IFNW1, and endothelial leukocyte migration, such as PRKCG and CXCL10 were found. These eGene families were linked to biological processes of innate and adaptive immune responses and associated with somatic cell scores in cattle, respectively. Our results may have implications for selecting desirable resistance traits in animals bred for production and highlight the importance of studying genetic variants involved in quantitative traits to improve our understanding of genetic mechanisms underlying gene expression regulation of adaptive traits in cattle.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149138"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nimbolide attenuates hepatocellular carcinoma by regulating miRNAs 21, 145 and 221 and their target gene expression.","authors":"Balasubramaniyan Vairappan, Victor Mukherjee, Siva Bala Subramanian, Amit Kumar Ram, T S Ravikumar","doi":"10.1016/j.gene.2024.149126","DOIUrl":"10.1016/j.gene.2024.149126","url":null,"abstract":"<p><strong>Background and aims: </strong>MicroRNAs (miRNAs) are becoming progressively emerging in cancer research from an etiologic and curative point of view. Several miRNAs act as oncogenes or tumor suppressors, which are dysregulated in numerous cancers. Our previous studies have established that nimbolide (a bioactive terpenoid from neem) attenuated hepatocellular carcinoma (HCC) through various mechanisms in mice. Here, we aimed to elucidate the effect of nimbolide in modulating specific miRNAs (21, 145, and 221) and their target genes involved in promoting inflammation and cancer cell proliferation in HCC mice.</p><p><strong>Methods: </strong>Following the induction of HCC in mice at 28 weeks, nimbolide (6 mg/kg b.wt.) was administered orally for four consecutive weeks.</p><p><strong>Results: </strong>We found significantly increased hepatic expression of miR-21a-3p, miR-21a-5p, miR-221-5p and miR-221-3p whilst significantly decreased miR-145a-5p in HCC mice. Nimbolide treatment to HCC mice substantially reduced the miR-21a-5p and miR-221-3p and improved miR-145a-5p gene expression. Our in-silico study also supports these findings. Moreover, hepatic tight junction (TJ) associated proteins such as claudins 1&5 mRNA and protein were increased considerably, whilst significantly decreased hepatic claudin 2 mRNA and protein expression noted in HCC mice. Nimbolide also regulates cadherins, ROCK 1, MMP 9, cyclin D1, CDK4, NF κB and TNFα mRNA expression in HCC mice.</p><p><strong>Conclusion: </strong>We identified for the first time that nibmolide treatment to HCC mice significantly attenuated hepatic miRNAs 21 & 221 expressions and sheltered miR-145 expression. These findings were further confirmed with in-silico studies. Moreover, nibmolide treatment in HCC mice regulates miRNA target genes involved in cancer cell proliferation and inflammation, thereby attenuating HCC progression in mice.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149126"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VNN2 regulates hepatic steroid synthesis in response to dietary changes.","authors":"Siyu Zhang, Xiang Fang, Zhaochuan Wang, Farhad Bordbar, Jiefeng Lin, Manqing Liu, Zhenhui Li","doi":"10.1016/j.gene.2024.149128","DOIUrl":"10.1016/j.gene.2024.149128","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptor alpha (PPARα) plays a crucial role in regulating hepatic fat oxidation. Previous studies have identified VNN2 as a potential PPARα target gene in chicken liver. However, the specific function of VNN2 in hepatic lipid metabolism remains unclear. We utilized datasets GSM5764402, GSM5764403, GSE128340, GSE129840, and PRJEB44038 to investigate the expression pattern and potential function of VNN2 in chicken liver. Our analysis included RNA sequencing, qPCR, and triglyceride and total cholesterol assays for verification. Through analysis of single-cell RNA sequencing (scRNA-seq) data, we localized VNN2 expression at the cellular level and identified potential downstream targets of VNN2. We further examined these potential targets in VNN2 overexpressed and knockdown Leghorn male hepatoma (LMH) cells. Our findings revealed that VNN2 is highly expressed in hepatocytes with elevated lipid metabolism and steroid biosynthesis activity. This study confirms that VNN2 promotes steroid biosynthesis by upregulating MSMO1 and FDPS, providing new insights into its role in hepatic lipid metabolism.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149128"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The significance of exosomal non-coding RNAs (ncRNAs) in the metastasis of colorectal cancer and development of therapy resistance.","authors":"Omid Rahbar Farzam, Sahand Eslami, Ali Jafarizadeh, Sania Ghobadi Alamdari, Reza Dabbaghipour, Shima Alizadeh Nobari, Behzad Baradaran","doi":"10.1016/j.gene.2024.149141","DOIUrl":"10.1016/j.gene.2024.149141","url":null,"abstract":"<p><p>Colorectal cancer (CRC) represents a common type of carcinoma with significant mortality rates globally. A primary factor contributing to the unfavorable treatment outcomes and reduced survival rates in CRC patients is the occurrence of metastasis. Various intricate molecular mechanisms are implicated in the metastatic process, leading to mortality among individuals with CRC. In the realm of intercellular communication, exosomes, which are a form of extracellular vesicle (EV), play an essential role. These vesicles act as conduits for information exchange between cells and originate from multiple sources. By fostering a microenvironment conducive to CRC progression, exosomes and EVs significantly influence the advancement of the disease. They contain a diverse array of molecules, including messenger RNAs (mRNAs), non-coding RNAs (ncRNAs), proteins, lipids, and transcription factors. Notably, ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are prominently featured within exosomes. These ncRNAs have the capacity to regulate various critical molecules or signaling pathways, particularly those associated with tumor metastasis, thereby playing a crucial role in tumorigenesis. Their presence indicates a substantial potential to affect vital aspects of tumor progression, including proliferation, metastasis, and resistance to treatment. This research aims to categorize exosomal ncRNAs and examine their functions in colorectal cancer. Furthermore, it investigates the clinical applicability of novel biomarkers and therapeutic strategies in CRC. Abbreviations: ncRNAs, non-coding RNAs; CRC, Colorectal cancer; EV, extracellular vesicle; mRNAs, messenger RNAs; miRNAs, microRNAs; lncRNAs, long non-coding RNAs; circRNAs, circular RNAs; HOTTIP, HOXA transcript at the distal tip; NSCLC, non-small cell lung cancer; 5-FU, 5-fluorouracil; OX, Oxaliplatin; PDCD4, programmed cell death factor 4; Tregs, regulatory T cells; EMT, epithelial-mesenchymal transition; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3; USP2, ubiquitin carboxyl-terminal hydrolase 2; TNM, tumor node metastasis; TAMs, tumor-associated macrophages; RASA1, RAS p21 protein activator 1; PDCD4, programmed cell death 4; ZBTB2, zinc finger and BTB domain containing 2; SOCS1, suppressor of cytokine signaling 1; TUBB3, β-III tubulin; MSCs, mesenchymal stem cells.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149141"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation and validation of neurotransmitter receptor-related biomarkers for forecasting clinical outcomes and immunotherapeutic efficacy in breast cancer.","authors":"Yili Li, Han Gao","doi":"10.1016/j.gene.2024.149135","DOIUrl":"10.1016/j.gene.2024.149135","url":null,"abstract":"<p><strong>Purpose: </strong>The prognostic role of neurotransmitters and their receptors in breast cancer (BC) has not been fully investigated. The aim of this study was to construct a survival model for the prognosis of BC patients based on neurotransmitter receptor-related genes (NRRGs).</p><p><strong>Methods: </strong>BC-related differentially expressed genes (DEGs) were screened and intersected with NRRGs. GO, KEGG and PPI analyses were performed. Univariate Cox, Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used to construct prognostic models for biomarker expression levels. The model was validated using an external validation set. The receiver operating characteristic curves (ROC) for diagnostic value prediction and clinicopathologic characteristic nomogram were constructed. qRT-PCR was used for further in vitro validation experiments.</p><p><strong>Results: </strong>Forty-five overlapping genes were obtained by intersecting BC-related DEGs with 172 NRRGs. Univariate Cox, LASSO and multivariate Cox regression analyses were used to construct prognostic models for the expression levels of biomarkers including DLG3, SLC1A1, PSCA and PRKCZ. The feasibility of the model was validated by the GEO validation set. ROC curves were established for diagnostic value prediction. Patients in the high-risk group had a worse prognosis, higher TMB score, higher probability of gene mutation, and higher immune cell infiltration. RiskScore, M, N and Age were strongly correlated with survival. The mRNA expression levels of DLG3, PSCA and PRKCZ in the BC group were significantly higher than those in the control group.</p><p><strong>Conclusion: </strong>Risk prediction model based on DLG3, SLC1A1, PSCA and PRKCZ, which are closely related to BC prognosis, was successfully constructed.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149135"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of glutaminyl-peptide cyclo-transferase-like protein (QPCTL) in cancer: From molecular mechanisms to immunotherapy.","authors":"Enwa Felix Oghenemaro, Subasini Uthirapathy, Deepak Nathiya, Parjinder Kaur, M Ravi Kumar, Ashish Verma","doi":"10.1016/j.gene.2024.149153","DOIUrl":"10.1016/j.gene.2024.149153","url":null,"abstract":"<p><p>Glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a newly discovered enzyme that has sparked interest owing to its possible role in cancer genesis and progression. Initially discovered as a post-translational modification regulator of protein maturation, QPCTL has emerged as a key participant in cancer biology. Recent research has linked QPCTL to numerous essential cancer-related processes, including cell proliferation, migration, invasion, and apoptosis. Furthermore, QPCTL expression changes have been seen in a variety of cancer types, underlining its potential as a diagnostic and prognostic marker. The molecular mechanisms behind QPCTL's participation in cancer will be examined in this review. We investigate its involvement in the control of signaling pathways and the modification of cellular activities that are important in cancer. We also examine the clinical importance of QPCTL, including as its relationship with tumor development, metastasis, and response to treatment. We also discuss the possible therapeutic implications of targeting QPCTL in cancer therapy. QPCTL is a prospective target for the development of innovative anticancer treatments due to its participation in several cancer-associated pathways.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149153"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phylogenetic studies and distinction of aflatoxin-producing Aspergillus species in section Flavi, Ochraceorosei and Nidulantes: A review.","authors":"Aashish Kumar Sharma, Adesh Kumar, Robin Rijal","doi":"10.1016/j.gene.2024.149151","DOIUrl":"10.1016/j.gene.2024.149151","url":null,"abstract":"<p><p>Aspergillus species produce polyketides, which form the basis of aflatoxins, some of the most significant mycotoxins in agriculture. Aflatoxins contaminate cereals, oilseeds, and nuts, both in the field and during storage. Of the 13 naturally occurring aflatoxins, the most potent are aflatoxins B₁, B₂, G₁, and G₂. The primary aflatoxigenic species are A. flavus, A. parasiticus, and A. nomius, while A. arachidicola, A. minisclerotigenes, and A. saccharicola also documented. These aflatoxin producers belong to three sections- 'Flavi', 'Ochraceorosei', and 'Nidulantes.' Aspergillus flavus, within section Flavi, shows morphological diversity, classified into Group I (S- and L- strains) and Group II (S- strains), with S-strains producing higher levels of aflatoxins. Aflatoxin biosynthesis is primarily regulated by the aflR gene, though other genes like aflS, aflP, aflQ, aflC, and aflM are also associated. However, presence of the aflR gene does not guarantee aflatoxin production across species. Sterigmatocystin serves as a precursor molecule within the pathway leading to aflatoxin production. Phylogenetic assessment, using ITS, BenA, CaM, and RBP2 gene sequences, reveals distinct clusters within Aspergillus sections and highlights the co-evolution of aflatoxigenic and non-aflatoxigenic species. Aspergillus ochraceoroseus and A. rambellii diverged out of aflatoxin-producing species earlier in evolutionary history, before splitting from a shared ancestor with A. fumigatus, which neither produces aflatoxins nor sterigmatocystin. Non-aflatoxigenic species like A. oryzae may evolve from aflatoxigenic species like A. flavus due to variations in evolutionary rates, telomere deletions, and mutations in aflatoxin biosynthesis genes. Comparative genomic analysis of AF, AF/ST and ST gene cluster shows that A. flavus has a larger aflatoxin gene cluster, while A. ochraceoroseus lacks the genes aflP and aflQ. Additionally, A. ochraceoroseus and A. rambellii possess a smaller genome, suggesting that genetic drift and deletions have refined their genomes for more efficient aflatoxin production.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149151"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}