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ContigPolishing: A User-Friendly Java GUI for contig extension and refinement in prokaryotic genomes ContigPolishing：一个用户友好的Java GUI，用于原核生物基因组的contig扩展和细化。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-13 DOI: 10.1016/j.gene.2025.149893

Rosyely da Silva Oliveira , Nilson César Oliveira Alves Filho , Walter de Barros Gomes Netto , Denis de Castro Silva , Mônica Silva de Oliveira , Ana Carolina Favacho Miranda de Oliveira , Rafael Azevedo Baraúna , Diego Assis das Graças , Artur Silva , Adonney Allan de Oliveira Veras

To determine the gene content of an organism, the reads generated by the sequencing process must be assembled using an assembly strategy, either by reference or de novo. However, this process often results in multiple sequences called contigs, which, after the sorting steps, are grouped into scaffolds. The completion stage aims to obtain a single genomic sequence, called a complete genome, which is not a trivial task. Various analytical strategies have been developed to help in this process, many of which have been implemented in computer tools to obtain complete genomes or as close to this as possible, the so-called drafts. The manuscript presents ContigPolishing, a computational tool with a simple and intuitive graphical interface, developed to improve the assembly of prokaryotic genomes, such as bacteria and metagenomes. Despite existing software, there is a gap for solutions that combine simplicity and robustness. ContigPolishing addresses this need, featuring an integrated database that allows processing to be resumed at any time. The tool was validated with 90 NCBI datasets from genera such as Escherichia coli, Corynebacterium, and Nocardia, as well as raw reads from the SRA database to simulate real-world situations. The results showed improvement in the contiguity of the assemblies, with an increase in N50 and improvement in L50, and a reduction in the number of contigs, by extending the contigs using the similarity between their flanks. In some cases, the software was able to elevate the status of genomes from draft to complete, proving its efficiency. ContigPolishing is available at: https://github.com/allanverasce/contigpolishing.

为了确定生物体的基因含量，测序过程产生的reads必须使用一种组装策略进行组装，要么是参照，要么是从头组装。然而，这个过程通常会产生称为contigs的多个序列，这些序列在排序步骤之后被分组为支架。完成阶段的目的是获得一个单一的基因组序列，称为完整的基因组，这不是一项微不足道的任务。已经开发了各种分析策略来帮助这个过程，其中许多已经在计算机工具中实现，以获得完整的基因组或尽可能接近于此，即所谓的草稿。该手稿介绍了ContigPolishing，这是一个具有简单直观图形界面的计算工具，用于改进原核生物基因组（如细菌和宏基因组）的组装。尽管有现有的软件，但结合了简单性和健壮性的解决方案仍然存在差距。ContigPolishing解决了这一需求，其特点是集成了数据库，允许在任何时候恢复处理。该工具使用90个NCBI数据集进行验证，这些数据集来自大肠杆菌、棒状杆菌和诺卡菌属，以及SRA数据库的原始读数，以模拟现实世界的情况。结果表明，通过利用其侧翼之间的相似性扩展contigs，提高了N50和L50的连续性，减少了contigs的数量。在某些情况下，该软件能够将基因组的状态从草稿提升到完成，证明了它的效率。ContigPolishing网站：https://github.com/allanverasce/contigpolishing。

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引用次数: 0

Combined genomic profiling by exome sequencing analysis and optical genome mapping reveals bi-allelic somatic inactivation of SMAD4 in pediatric colon adenocarcinoma 结合外显子组测序分析和光学基因组定位的基因组分析揭示了儿童结肠腺癌中SMAD4双等位基因的体细胞失活。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-12 DOI: 10.1016/j.gene.2025.149891

Mari C. Morán-Espinosa , Aldo Zaragoza-Fernández , Karem Yohaly Pérez-López , Cristian Jesús Huchim-Peña , Pedro Velarde-Hernández , María Argelia Escobar-Sánchez , Rodrigo Moreno-Salgado , Rocío Sánchez-Urbina , Hector Diaz-Garcia , Guillermo Aquino Jarquin , Javier T. Granados-Riverón

引用次数: 0

Genetic diversity, natural selection, and immunological features of the Plasmodium vivax CyRPA protein: Implications for vaccine development 间日疟原虫CyRPA蛋白的遗传多样性、自然选择和免疫学特征：对疫苗开发的影响。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-12 DOI: 10.1016/j.gene.2025.149894

Diego Garzón-Ospina , Sindy P. Buitrago , Natalia Cepeda-Riaño , Carlos J. Castro-Cavadía , María Fernanda Yasnot-Acosta

Malaria caused by Plasmodium vivax remains a significant public health challenge, with vaccine development hindered by factors such as antigenic diversity and immune evasion. The Cysteine-Rich Protective Antigen (CyRPA), a key protein involved in erythrocyte invasion, has emerged as a promising vaccine candidate. However, its genetic diversity and immunological properties have not been fully explored. This study aimed to analyze the genetic diversity, selective pressures, and antigenic potential of the pvcyrpa locus using 950 sequences, including 42 newly obtained isolates from Colombia. The pvcyrpa gene displayed high nucleotide diversity shaped by both natural selection and recombination. In-silico predictions identified B- and T-cell epitopes, encompassing mainly polymorphic regions, with strong binding affinities predicted for multiple HLA alleles. Notably, these epitopes overlapped with regions previously shown to elicit immune responses in natural infections, as reported in a recent study. Moreover, immune simulation of a multiepitope C-terminal construct predicted a robust humoral memory profile. Collectively, these genetic, epitope-mapping, and immune-simulation findings highlight the conserved C-terminal region of PvCyRPA as a strong, broadly reactive vaccine candidate, providing a rational basis for subsequent in-vitro and in-vivo validation.

间日疟原虫引起的疟疾仍然是一个重大的公共卫生挑战，疫苗的开发受到抗原多样性和免疫逃避等因素的阻碍。富含半胱氨酸保护性抗原（CyRPA）是参与红细胞侵袭的关键蛋白，已成为一种有希望的候选疫苗。然而，其遗传多样性和免疫学特性尚未得到充分的研究。本研究利用哥伦比亚新获得的42株pvcyrpa菌株的950个序列，分析了pvcyrpa基因座的遗传多样性、选择压力和抗原性。pvcyrpa基因在自然选择和重组的双重作用下表现出高度的核苷酸多样性。计算机预测确定了B细胞和t细胞表位，主要包括多态性区域，预测多个HLA等位基因具有很强的结合亲和力。值得注意的是，在最近的一项研究中，这些表位与先前显示的在自然感染中引起免疫反应的区域重叠。此外，多表位c末端构建的免疫模拟预测了强大的体液记忆谱。总的来说，这些遗传、表位定位和免疫模拟的发现突出了PvCyRPA的保守c端区域是一个强大的、广泛反应性的候选疫苗，为随后的体外和体内验证提供了合理的基础。

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引用次数: 0

Retraction notice to “Association between -251A> T polymorphism in the interleukin-8 gene and oral cancer risk: a meta-analysis.” [Gene 522 (2013) 168–176] “白细胞介素-8基因-251A> T多态性与口腔癌风险之间的关系：一项荟萃分析”的撤回通知。[基因522(2013)168-176]。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-11 DOI: 10.1016/j.gene.2025.149875

Zhiming Wang, Chuanning Wang, Zhiguo Zhao, Fang Liu, Xinming Guan, Xiaoping Lin, Liping Zhang

引用次数: 0

Mettl1 mitigates sepsis-induced cardiomyopathy via inhibition of FDX1-dependent cuproptosis Mettl1通过抑制fdx1依赖性铜体增生减轻败血症引起的心肌病。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-11 DOI: 10.1016/j.gene.2025.149892

Wei Siang , Wang Guoyun , Feng Yan , Lin Wenji

Sepsis-induced cardiomyopathy (SICM) significantly contributes to sepsis-related mortality, yet its molecular mechanisms remain incompletely understood. Here, we identify cuproptosis—a copper-dependent mitochondrial cell death pathway—as a critical driver of SICM pathogenesis. In a murine SICM model induced by lipopolysaccharide (LPS), cardiac dysfunction was accompanied by myocardial copper accumulation and dysregulation of cuproptosis regulators. RNA sequencing (RNA-seq) analysis revealed cuproptosis as one of the top enriched pathways. Crucially, we demonstrate that the m7G methyltransferase Mettl1 functions as a cardioprotective factor. Mettl1 expression was upregulated in septic hearts and positively correlated with copper levels. In vitro, Mettl1 knockdown exacerbated LPS-induced cytotoxicity in cardiomyocytes and amplified intracellular copper overload. Mechanistically, Mettl1 deficiency potentiated LPS-triggered upregulation of FDX1—a key executor of cuproptosis—and suppressed PDHA1 expression. Our findings establish Mettl1 as a novel suppressor of cuproptosis that confers protection against sepsis-induced cardiotoxicity by restraining FDX1-mediated copper-dependent cell death. Targeting the Mettl1-FDX1 axis may offer a promising therapeutic strategy for SICM.

败血症性心肌病（SICM）是导致败血症相关死亡率的重要因素，但其分子机制尚不完全清楚。在这里，我们发现铜细胞凋亡——一种依赖铜的线粒体细胞死亡途径——是SICM发病机制的一个关键驱动因素。在脂多糖（LPS）诱导的小鼠SICM模型中，心功能障碍伴随着心肌铜积累和铜增生调节因子的失调。RNA测序（RNA-seq）分析显示cuprotosis是最富集的途径之一。至关重要的是，我们证明了m7G甲基转移酶Mettl1作为一种心脏保护因子发挥作用。Mettl1在脓毒症心脏中表达上调，且与铜水平呈正相关。在体外，Mettl1敲低加剧了lps诱导的心肌细胞毒性，并放大了细胞内铜超载。从机制上讲，Mettl1缺乏增强了lps触发的fdx1（铜生长的关键执行者）的上调，并抑制了PDHA1的表达。我们的研究结果表明，Mettl1是一种新的铜增生抑制因子，通过抑制fdx1介导的铜依赖性细胞死亡，可以防止败血症诱导的心脏毒性。靶向Mettl1-FDX1轴可能为SICM提供一种有希望的治疗策略。

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引用次数: 0

β-catenin/TCF4/NANOG axis controls miR-302 transcription in colorectal cancer cells β-catenin/TCF4/NANOG轴控制结直肠癌细胞中miR-302的转录。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-10 DOI: 10.1016/j.gene.2025.149890

Kiarash Saleki , Miao Xue , Amirreza Mazloomi , Bradley Spencer-Dene , Abdolrahman S. Nateri

The miR-302 cluster, a key pluripotency-associated non-coding RNA, has been implicated in stem cell homeostasis and tumourigenesis. However, its regulatory mechanisms in cancers, including colorectal cancer (CRC) remain poorly understood. Here, we demonstrate that the β-catenin/TCF4 complex significantly enhances miR-302 expression through direct promoter activation in CRC cells. We hypothesized that the β-catenin/TCF4 complex directly activates the miR-302 promoter and cooperates with NANOG in a transcriptional feedback loop sustaining stem-like traits in CRC cells. Using a combination of promoter-driven luciferase reporter assays, chromatin immunoprecipitation (ChIP), and molecular dynamics simulations, we identify a regulatory axis involving Wnt signalling and the transcription factor NANOG. Our data show that individual members of the miR-302 cluster activate the NANOG promoter, while both NANOG and β-catenin/TCF4 synergistically enhance miR-302 promoter activity, suggesting the presence of a positive feedback loop. Structural simulations further elucidate the binding interactions between TCF4, NANOG, and the miR-302 promoter, corroborating our experimental observations. Together, these findings position miR-302 as a downstream effector of Wnt/β-catenin signalling and an integral component of NANOG-mediated transcriptional networks in CRC stem-like cells. This work advances our understanding of non-coding RNA regulation in cancer and highlights potential therapeutic opportunities for targeting stemness-associated pathways.

miR-302簇是一种关键的多能性相关非编码RNA，与干细胞稳态和肿瘤发生有关。然而，其在包括结直肠癌（CRC）在内的癌症中的调节机制仍然知之甚少。在这里，我们证明β-catenin/TCF4复合物通过直接启动子激活在CRC细胞中显著增强miR-302的表达。我们假设β-catenin/TCF4复合物直接激活miR-302启动子，并在维持CRC细胞干样性状的转录反馈回路中与NANOG合作。通过结合启动子驱动的荧光素酶报告子测定、染色质免疫沉淀（ChIP）和分子动力学模拟，我们确定了一个涉及Wnt信号和转录因子NANOG的调控轴。我们的数据显示，miR-302集群的单个成员激活NANOG启动子，而NANOG和β-catenin/TCF4协同增强miR-302启动子活性，表明存在正反馈回路。结构模拟进一步阐明了TCF4、NANOG和miR-302启动子之间的结合相互作用，证实了我们的实验观察。总之，这些发现表明miR-302是Wnt/β-catenin信号传导的下游效应因子，也是CRC干细胞样细胞中nanog介导的转录网络的一个组成部分。这项工作促进了我们对癌症中非编码RNA调控的理解，并强调了针对干细胞相关途径的潜在治疗机会。

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引用次数: 0

Population structure analysis of eight goat breeds based on super-genotyping-by-sequencing 基于超基因分型测序的8个山羊品种群体结构分析。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-10 DOI: 10.1016/j.gene.2025.149877

Xiangzhen Gou , Keyan Ma , Junxiang Yang , Ke Wang , Yuqin Ma

China harbors rich indigenous goat resources. However, factors such as the introduction of exotic breeds and crossbreeding have led to a decline in local populations and obscured genetic structures. Consequently, it is imperative to conduct genetic diversity and population structure assessments of key indigenous goat populations. This study employed Super-GBS sequencing technology to evaluate genetic diversity and population structure in eight goat breeds (n = 211), and further identified candidate genes associated with production traits and environmental adaptation through selection signature analysis. Ziwuling black goat (ZWL) exhibited the highest diversity, whereas Dazu black goat (DZH) showed the lowest. Pairwise F_ST revealed strong differentiation between DZH and Liaoning cashmere / Inner Mongolia cashmere goat (NMC) (0.1221) due to geographic isolation, but negligible divergence between Ziwuling cashmere (ZWLH) and Hexi cashmere (HXC) (0.0066), indicating gene flow. Population structure resolved three clades: DZH as an independent lineage, Yimeng black goat (YMH) clustering with ZWL, and multiple cashmere subgroups. Runs of homozygosity (ROH) revealed elevated inbreeding in DZH (F_ROH = 0.178) versus lower levels in cashmere breeds (0.071–0.098). Selective sweeps identified 252 genes linked to cashmere traits, including DCN, SEMA3D, FGF5, enriched in TGF-β, MAPK, and circadian rhythm pathways regulating hair follicle cycling. Comparative scans between arid-adapted NMC and subtropical DZH identified 372 genes (e.g., MTOR, ROBO2, PPP3CA) involved in thermogenesis, water reabsorption, and hypoxia response. Together, these findings highlight how artificial selection and environmental adaptation jointly shape goat genomic architecture. Conservation should prioritize populations with declining diversity (e.g., ZWLH, SXC) and implement controlled breeding to reduce inbreeding, thereby safeguarding agro-biodiversity and sustainable utilization.

中国拥有丰富的本土山羊资源。然而，外来品种的引进和杂交等因素导致了当地种群的减少和遗传结构的模糊。因此，对主要地方山羊种群进行遗传多样性和种群结构评估势在必行。本研究采用Super-GBS测序技术对8个山羊品种（n = 211）的遗传多样性和群体结构进行了分析，并通过选择特征分析进一步确定了与生产性状和环境适应相关的候选基因。子午岭黑山羊（ZWL）多样性最高，大足黑山羊（DZH）多样性最低。两两FST结果显示，由于地理隔离，DZH与辽宁绒山羊/内蒙绒山羊（NMC）差异较大（0.1221），而子乌岭绒山羊（ZWLH）与河西绒山羊（HXC）差异较小（0.0066），提示基因流动。种群结构划分为三个支系：DZH为独立支系，沂蒙黑山羊（YMH）与ZWL聚类，羊绒亚群多。纯合性分析（ROH）显示，DZH品种近交率升高（FROH = 0.178），而羊绒品种近交率较低（0.071 ~ 0.098）。选择性扫描鉴定出252个与羊绒性状相关的基因，包括DCN、SEMA3D、FGF5、富含TGF-β、MAPK和调节毛囊循环的昼夜节律通路。干旱适应NMC和亚热带DZH的对比扫描鉴定出372个基因（如MTOR、ROBO2、PPP3CA）参与产热、水重吸收和缺氧反应。总之，这些发现强调了人工选择和环境适应如何共同塑造山羊的基因组结构。保护应优先考虑多样性下降的种群（如ZWLH、SXC），并实施控制育种，减少近亲繁殖，从而保护农业生物多样性和可持续利用。

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引用次数: 0

NR1D1 in tumorigenesis: dual roles, mechanisms, and therapeutic targeting NR1D1在肿瘤发生中的双重作用、机制和治疗靶向。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-09 DOI: 10.1016/j.gene.2025.149889

Zhuangwei Lv , Ruohao Yang , Jinhua Wu , Xiaoyu Shi , Ruihan Wang , Yi’ang Niu , Zhuang Qian , Junna Jiao , Yunfeng Ma

Nuclear receptor subfamily 1, group D, member 1 (NR1D1, also known as REV-ERBα), a core circadian regulator, plays context-dependent dual roles in cancer, acting as either a tumor suppressor or oncogene. This review synthesizes current evidence on NR1D1’s regulation of key oncogenic pathways: DNA repair, immunomodulation (e.g., the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, NOD-like receptor family pyrin domain containing 3(NLRP3)), metabolism, and signaling cascades such as PI3K/AKT, JAK/STAT. We highlight its clinical utility as a prognostic biomarker and therapeutic target, focusing on pharmacological modulators with demonstrated preclinical efficacy. We also critically discuss challenges in targeting NR1D1 and its potential in combination therapies, offering new insights for cancer treatment.

核受体亚家族1，D组，成员1 (NR1D1，也称为rev - erba)，是一个核心的昼夜节律调节因子，在癌症中起着环境依赖的双重作用，既可以作为肿瘤抑制因子，也可以作为致癌基因。本文综述了NR1D1调控主要致癌通路的现有证据：DNA修复、免疫调节(如环GMP-AMP合成酶（cGAS)-干扰素基因刺激因子（STING）通路、nod样受体家族pyrin结构域3(NLRP3)）、代谢和信号级联如PI3K/AKT、JAK/STAT。我们强调其作为预后生物标志物和治疗靶点的临床应用，重点关注具有临床前疗效的药理学调节剂。我们还批判性地讨论了靶向NR1D1的挑战及其在联合治疗中的潜力，为癌症治疗提供了新的见解。

引用次数: 0

Double minutes: exploring the formation and oncogenic roles in cancer progression 双分钟：探索癌症进展中的形成和致癌作用。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-08 DOI: 10.1016/j.gene.2025.149879

Mahjabin Sanam, Chowdhury Fatema Tuz Zohra Hossain, Jahin Fairuj Oishi, Reasat Tarannum, Nusrat Zahan Rouf

ecDNA is a circular DNA extensively present in human cancers, particularly advanced tumors, but rarely detected in healthy cells. Previously, they were named “minute chromatin bodies,” which eventually changed into “Double minutes (DMs)” as they exist in pairs. Due to their structural and epigenetic modifications, they confer specific advantages, helping them to survive and persist within cells. Rapid amplification of drug-resistant genes or oncogenes, increased chromatin accessibility, and non-Mendelian inheritance all contribute significantly to tumor adaptability, aggressiveness, and resistance to drug or chemotherapy treatment. Thus, this review paper aims to discuss DMs’ formation, mechanism, and maintenance, examining the tools used to detect them and investigating the commonly observed oncogenes in different cancer types. Lastly, the therapeutic approaches applied over the years have been to reduce or eliminate DMs in tumor cells.

ecDNA是一种环状DNA，广泛存在于人类癌症，特别是晚期肿瘤中，但很少在健康细胞中检测到。以前，它们被命名为“分钟染色质体”，最终变成了“双分钟（dm）”，因为它们成对存在。由于它们的结构和表观遗传修饰，它们赋予了特定的优势，帮助它们在细胞内存活和持续存在。耐药基因或癌基因的快速扩增、染色质可及性的增加和非孟德尔遗传都对肿瘤的适应性、侵袭性和对药物或化疗的耐药性有重要作用。因此，本文旨在讨论DMs的形成、机制和维持，研究用于检测DMs的工具，并研究不同类型癌症中常见的致癌基因。最后，多年来应用的治疗方法是减少或消除肿瘤细胞中的DMs。

引用次数: 0

Functional analysis of two component signaling system in Mycobacterium tuberculosis 结核分枝杆菌双组分信号系统的功能分析。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2025-11-07 DOI: 10.1016/j.gene.2025.149868

Karthikeyan Sundaram , Sridhar Rathinam

Tuberculosis is a fatal infection transmitted through airborne droplet nuclei. The etiological agent is Mycobacterium tuberculosis, an acid-fast bacillus. Drug-resistant tuberculosis poses a global challenge, with specific mycobacterial genes intricately associated with drug resistance. Numerous factors are implicated in the etiology of the condition. This review specifically aims to examine ClpCP, an ATPase belonging to the AAA + protease family, and the genes of the two-component sensor system related with disease etiology. Mycobacterium TB depends significantly on protein degradation to regulate their quantity and quality, which is crucial for its proliferation and pathogenicity involving Clp. The two-component sensor system comprises histidine kinase (HK) and response regulator (RR), which governs responses to stress situations, starvation, nutritional abundance, persistence, hypoxia, dormancy, and primarily disease pathogenesis. Within the two-component system, there exist 12 pairs, including SenX3/RegX3, PhoP/PhoR, DosR/DosS, MtrA/MtrB, and PdtaS/PdtaR, alongside 6 response regulators Rv0195, Rv0260c, Rv0818, PdtaR, Rv2884, and Rv3143 encoded in the Mycobacterium tuberculosis genome. The PhoPR genes have been extensively researched, and the pathogenicity of Mycobacterium tuberculosis (MTB) is contingent upon the sensor kinase of the PhoPR two-component regulatory system, known as PhoR. This review will examine the roles of genes related to the factors associated with mycobacterial growth and pathogenesis.

结核病是一种通过空气传播的飞沫核传播的致命传染病。病原是结核分枝杆菌，一种抗酸杆菌。耐药结核病是一项全球性挑战，特定的分枝杆菌基因与耐药有着错综复杂的关系。许多因素涉及到该病的病因学。这篇综述特别旨在研究ClpCP，一种属于AAA + 蛋白酶家族的atp酶，以及与疾病病因相关的双组分传感器系统基因。结核分枝杆菌主要依靠蛋白质降解来调节其数量和质量，这对其涉及Clp的增殖和致病性至关重要。这种双组分传感器系统包括组氨酸激酶（HK）和反应调节因子（RR），它们控制对应激情况、饥饿、营养丰富、持久性、缺氧、休眠和主要疾病发病机制的反应。在双组分体系中，共编码SenX3/RegX3、PhoP/PhoR、DosR/DosS、MtrA/MtrB、PdtaS/PdtaR等12对，以及Rv0195、Rv0260c、Rv0818、PdtaR、Rv2884、Rv3143 6个应答调控因子。PhoPR基因已被广泛研究，结核分枝杆菌（MTB）的致病性取决于PhoPR双组分调控系统（PhoR）的传感器激酶。本文将探讨与分枝杆菌生长和发病相关的基因的作用。

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