orthologs

Orthologs
  • 文章类型: Journal Article
    油菜素类固醇(BRs)是一组重要的植物激素,调节植物生长的许多方面,发展,和应激反应。BRI1及其共受体BAK1参与BR信号转导级联中的油菜素类固醇传感和早期事件。特定基因的突变分析是研究其生化作用的有力策略。分子遗传学研究,主要在拟南芥,但在许多其他植物中,已经鉴定了BRI1基因及其直系同源物的许多突变体,以深入了解其结构和功能。到目前为止,植物界在拟南芥中鉴定出多达40个bri1等位基因,在不同植物中鉴定出多达30个bri1直向同源物。这些等位基因表现出在发育和生长方面相同的表型。这里,我们总结了拟南芥中的bri1等位基因及其在各种植物中存在的直系同源物,包括单子叶植物和双子叶植物。我们已经讨论了负责特定等位基因的可能机制。最后,我们已经简单地讨论了这些等位基因在研究领域的重要性,以及它们提供的农学上有价值的性状,以改善植物品种。
    Brassinosteroids (BRs) are an essential group of plant hormones regulating numerous aspects of plant growth, development, and stress responses. BRI1, along with its co-receptor BAK1, are involved in brassinosteroid sensing and early events in the BR signal transduction cascade. Mutational analysis of a particular gene is a powerful strategy for investigating its biochemical role. Molecular genetic studies, predominantly in Arabidopsis thaliana, but progressively in numerous other plants, have identified many mutants of the BRI1 gene and its orthologs to gain insight into its structure and function. So far, the plant kingdom has identified up to 40 bri1 alleles in Arabidopsis and up to 30 bri1 orthologs in different plants. These alleles exhibit phenotypes that are identical in terms of development and growth. Here, we have summarized bri1 alleles in Arabidopsis and its orthologs present in various plants including monocots and dicots. We have discussed the possible mechanism responsible for the specific allele. Finally, we have briefly debated the importance of these alleles in the research field and the agronomically valuable traits they offer to improve plant varieties.
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  • 文章类型: Journal Article
    人类基因组中的调谐直向同源物仅包含19,872个蛋白质编码基因中的84个基因和16,528个非编码基因中的23个,但它们却站在Olfactores进化枝的底部,辐射产生数千种被膜动物和脊椎动物。这些基因中有哪些强大的驱动因素促成了这一过程?许多这些直系同源物存在于基因家族中。我们讨论了每个家庭的生物学作用以及直系同源物对家庭的定量贡献。最重要的是第二种钙粘蛋白的进化。这个,一种II型钙黏着蛋白,具有从表达I型类别的细胞中分离含有该钙黏着蛋白的细胞的性质。这种II型钙粘蛋白的集合现在可以脱离并远离它们的I型邻居,这个过程最终会演变成神经峰的形成,“第四胚层”,为进一步的进化发明提供了广泛的可能性。第二个重要贡献是对肌肉和神经蛋白以及视觉感知工具包的广泛开发的关键补充。机动性和视野方面的这些发展为Vertebrata的有效掠夺性能力的发展提供了基础。
    Tunicate orthologs in the human genome comprise just 84 genes of the 19,872 protein-coding genes and 23 of the 16,528 non-coding genes, yet they stand at the base of the Olfactores clade, which radiated to generate thousands of tunicate and vertebrate species. What were the powerful drivers among these genes that enabled this process? Many of these orthologs are present in gene families. We discuss the biological role of each family and the orthologs\' quantitative contribution to the family. Most important was the evolution of a second type of cadherin. This, a Type II cadherin, had the property of detaching the cell containing that cadherin from cells that expressed the Type I class. The set of such Type II cadherins could now detach and move away from their Type I neighbours, a process which would eventually evolve into the formation of the neural crest, \"the fourth germ layer\", providing a wide range of possibilities for further evolutionary invention. A second important contribution were key additions to the broad development of the muscle and nerve protein and visual perception toolkits. These developments in mobility and vision provided the basis for the development of the efficient predatory capabilities of the Vertebrata.
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  • 文章类型: Journal Article
    终端镰刀菌(TFC)是Nectriaceae家族中的一组,具有农业和临床相关性。近年来,各种系统发育已经在文献中提出,显示拓扑结构中的分歧,但是只有少数研究对群体的分歧时间尺度进行了分析。因此,这个群体的进化历史仍在确定中。本研究旨在从系统发育学的角度了解TFC的进化史。为了实现这一目标,我们使用GenBank中可用的基因组进行了系统基因组分析,并运行了8个不同的管道.我们提出了一种新的TFC鲁棒拓扑结构,该结构在某些节点上与以前的研究不同。这些新的关系使我们能够提出有关TFC进化史的新假设。我们还推断了新的发散时间估计,由于拓扑结构不一致和分类单元采样,这与以前的研究不同。结果表明,新近纪有一个重要的多元化过程,可能与被子植物对陆地生态系统的多样化和优势有关。总之,我们提出了一个强大的时间尺度系统发育,使我们能够提出有关TFC进化史的新假设。
    The Terminal Fusarium Clade (TFC) is a group in the Nectriaceae family with agricultural and clinical relevance. In recent years, various phylogenies have been presented in the literature, showing disagreement in the topologies, but only a few studies have conducted analyses on the divergence time scale of the group. Therefore, the evolutionary history of this group is still being determined. This study aimed to understand the evolutionary history of the TFC from a phylogenomic perspective. To achieve this objective, we performed a phylogenomic analysis using the available genomes in GenBank and ran eight different pipelines. We presented a new robust topology of the TFC that differs at some nodes from previous studies. These new relationships allowed us to formulate new hypotheses about the evolutionary history of the TFC. We also inferred new divergence time estimates, which differ from those of previous studies due to topology discordances and taxon sampling. The results suggested an important diversification process in the Neogene period, likely associated with the diversification and predominance of terrestrial ecosystems by angiosperms. In conclusion, we presented a robust time-scale phylogeny that allowed us to formulate new hypotheses regarding the evolutionary history of the TFC.
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  • 文章类型: Journal Article
    毛细胞(HC)是脊椎动物内耳中听觉和前庭系统的感觉受体,可将机械刺激选择性地转化为电活动。尽管所有HC都具有机械转导的标志性立体纤毛束,非哺乳动物和哺乳动物中的HCs在顶端的分子专业化方面有所不同,基底外侧和突触膜。非哺乳动物的HCs,如斑马鱼(zHCs),被电调谐到特定频率,并在立体纤毛束中具有主动过程以放大声音信号。哺乳动物耳蜗HC,相比之下,不进行电调谐,并通过外部HC(OHC)的体细胞运动性实现扩增。为了了解成年斑马鱼和哺乳动物耳蜗HCs之间差异的遗传机制,我们比较了他们的RNA-seq特征转录组,专注于与HC特化相关的蛋白质编码直系同源基因。在HC之间有相当多的基因直向同源物的共享表达,包括那些与机械转导相关的基因,离子传输/通道,和突触信号。例如,斑马鱼和小鼠HCs都表达Tmc1,Lhfpl5,Tmie,Cib2,Cacna1d,Cacnb2,Otof,Pclo和Slc17a8。然而,zHCs之间的表达有一些显着差异,OHCs,和内部HC(IHC),这可能是每种细胞类型独特的生理特性的基础。在成年小鼠HCs中未检测到Tmc2和Cib3,但tmc2a和b和Cib3在zHCs中高度表达。小鼠HCs表达Kcna10,Kcnj13,Kcnj16,和Kcnq4,在zHCs中未检测到。Chrna9和Chrna10在小鼠HC中表达。相比之下,在zHCs中未检测到chrna10。OHC高度表达Slc26a5,其编码有助于OHC电动性的运动蛋白prestin。然而,zHCs仅弱表达slc26a5,并随后在测量时显示没有电压依赖性的电运动性。值得注意的是,zHC表达更多的旁系同源基因,包括与HC特异性功能和转录活性相关的基因,尽管尚不清楚它们是否具有与哺乳动物对应物相似的功能。与已知听力表型相关的表达基因存在重叠。我们的分析揭示了基因表达模式的实质性差异,这可能解释了斑马鱼和小鼠HCs的表型特化。该数据集还包括几个蛋白质编码基因,以进一步表征HC的功能并研究HC从非哺乳动物到哺乳动物的进化。
    Hair cells (HCs) are the sensory receptors of the auditory and vestibular systems in the inner ears of vertebrates that selectively transduce mechanical stimuli into electrical activity. Although all HCs have the hallmark stereocilia bundle for mechanotransduction, HCs in non-mammals and mammals differ in their molecular specialization in the apical, basolateral and synaptic membranes. HCs of non-mammals, such as zebrafish (zHCs), are electrically tuned to specific frequencies and possess an active process in the stereocilia bundle to amplify sound signals. Mammalian cochlear HCs, in contrast, are not electrically tuned and achieve amplification by somatic motility of outer HCs (OHCs). To understand the genetic mechanisms underlying differences among adult zebrafish and mammalian cochlear HCs, we compared their RNA-seq-characterized transcriptomes, focusing on protein-coding orthologous genes related to HC specialization. There was considerable shared expression of gene orthologs among the HCs, including those genes associated with mechanotransduction, ion transport/channels, and synaptic signaling. For example, both zebrafish and mouse HCs express Tmc1, Lhfpl5, Tmie, Cib2, Cacna1d, Cacnb2, Otof, Pclo and Slc17a8. However, there were some notable differences in expression among zHCs, OHCs, and inner HCs (IHCs), which likely underlie the distinctive physiological properties of each cell type. Tmc2 and Cib3 were not detected in adult mouse HCs but tmc2a and b and cib3 were highly expressed in zHCs. Mouse HCs express Kcna10, Kcnj13, Kcnj16, and Kcnq4, which were not detected in zHCs. Chrna9 and Chrna10 were expressed in mouse HCs. In contrast, chrna10 was not detected in zHCs. OHCs highly express Slc26a5 which encodes the motor protein prestin that contributes to OHC electromotility. However, zHCs have only weak expression of slc26a5, and subsequently showed no voltage dependent electromotility when measured. Notably, the zHCs expressed more paralogous genes including those associated with HC-specific functions and transcriptional activity, though it is unknown whether they have functions similar to their mammalian counterparts. There was overlap in the expressed genes associated with a known hearing phenotype. Our analyses unveil substantial differences in gene expression patterns that may explain phenotypic specialization of zebrafish and mouse HCs. This dataset also includes several protein-coding genes to further the functional characterization of HCs and study of HC evolution from non-mammals to mammals.
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  • 文章类型: Journal Article
    大多数基因是进化相关基因的较大家族的一部分。基因家族的历史通常涉及基因的复制和丢失以及向其他生物体的水平转移。详细的基因家族史的重建,即,进化事件相对于基础物种的系统发育树的精确年代仍然是一个具有挑战性的话题,尽管它们作为详细研究基因家族单个成员的适应和功能进化的基础很重要。直系同源物的鉴定,此外,是这里考虑的更一般设置的一个特别重要的子问题。在过去的几年里,大量的数学结果已经出现,它们紧密地联系在一起,基因间最佳匹配的正式概念,和水平基因转移。本章的目的是大致概述一些关键的数学见解,并讨论它们对实际应用的启示。特别是,我们专注于无树方法,即,推断正交或水平基因转移以及基因树的方法,树种,以及它们之间的协调,而无需使用基础树的先验知识或统计模型来推断系统发育树。相反,第一步旨在提取基因之间的二元关系。
    Most genes are part of larger families of evolutionary-related genes. The history of gene families typically involves duplications and losses of genes as well as horizontal transfers into other organisms. The reconstruction of detailed gene family histories, i.e., the precise dating of evolutionary events relative to phylogenetic tree of the underlying species has remained a challenging topic despite their importance as a basis for detailed investigations into adaptation and functional evolution of individual members of the gene family. The identification of orthologs, moreover, is a particularly important subproblem of the more general setting considered here. In the last few years, an extensive body of mathematical results has appeared that tightly links orthology, a formal notion of best matches among genes, and horizontal gene transfer. The purpose of this chapter is to broadly outline some of the key mathematical insights and to discuss their implication for practical applications. In particular, we focus on tree-free methods, i.e., methods to infer orthology or horizontal gene transfer as well as gene trees, species trees, and reconciliations between them without using a priori knowledge of the underlying trees or statistical models for the inference of phylogenetic trees. Instead, the initial step aims to extract binary relations among genes.
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  • 文章类型: Journal Article
    背景:绿豆(Vignaradiata(L.)威尔切克),是全球南部重要的豆类作物。早期开花和成熟是适应北方和南方纬度的有利特征。本研究调查了绿豆开花天数性状(DTF)的遗传基础,结合绿豆的全基因组关联研究(GWAS),并与大豆(Glycinemax(L)Merr)和拟南芥(拟南芥)中DTF反应控制的直系同源基因进行比较。
    结果:DTF的最显著关联在绿豆染色体1、2和4上。使用下游分析仅大量研究了染色体1和4上的SNP。1号染色体DTF关联与一组局部重复的FERONIA(FER)受体样蛋白激酶基因紧密相关,SNP发生在一个FERONIA基因中。在拟南芥中,直系同源FERONIA基因(AT3G51550),已报道调节花斑C(FLC)的表达。对于4号染色体DTF基因座,最强的候选者是Vradi04g00002773和Vradi04g00002778,它们与拟南芥PhyA和PIF3基因直系同源,分别编码植物色素A(一种对红光到远红光敏感的感光蛋白)和植物色素相互作用因子3。大豆PhyA直向同源物包括经典基因座E3和E4(基因GmPhyA3,Glyma.19G224200和GmPhyA2,Glyma.20G090000)。在韩国进行的研究中,绿豆PhyA直系同源物先前已被报道为DTF的候选物。
    结论:前两个鉴定的SNP占绿豆DTF表型变异的显着比例(〜65%),由六个显着的SNP(39.61%),广义遗传力为0.93。DTF与在大豆和拟南芥中具有类似功能的直向同源物的基因的强烈关联提供了强有力的间接证据,证明这些基因是该性状的因果关系。报道的三个基因座和候选基因为绿豆标记辅助育种提供了有用的靶标。
    BACKGROUND: Mung bean (Vigna radiata (L.) Wilczek), is an important pulse crop in the global south. Early flowering and maturation are advantageous traits for adaptation to northern and southern latitudes. This study investigates the genetic basis of the Days-to-Flowering trait (DTF) in mung bean, combining genome-wide association studies (GWAS) in mung bean and comparisons with orthologous genes involved with control of DTF responses in soybean (Glycine max (L) Merr) and Arabidopsis (Arabidopsis thaliana).
    RESULTS: The most significant associations for DTF were on mung bean chromosomes 1, 2, and 4. Only the SNPs on chromosomes 1 and 4 were heavily investigated using downstream analysis. The chromosome 1 DTF association is tightly linked with a cluster of locally duplicated FERONIA (FER) receptor-like protein kinase genes, and the SNP occurs within one of the FERONIA genes. In Arabidopsis, an orthologous FERONIA gene (AT3G51550), has been reported to regulate the expression of the FLOWERING LOCUS C (FLC). For the chromosome 4 DTF locus, the strongest candidates are Vradi04g00002773 and Vradi04g00002778, orthologous to the Arabidopsis PhyA and PIF3 genes, encoding phytochrome A (a photoreceptor protein sensitive to red to far-red light) and phytochrome-interacting factor 3, respectively. The soybean PhyA orthologs include the classical loci E3 and E4 (genes GmPhyA3, Glyma.19G224200, and GmPhyA2, Glyma.20G090000). The mung bean PhyA ortholog has been previously reported as a candidate for DTF in studies conducted in South Korea.
    CONCLUSIONS: The top two identified SNPs accounted for a significant proportion (~ 65%) of the phenotypic variability in mung bean DTF by the six significant SNPs (39.61%), with a broad-sense heritability of 0.93. The strong associations of DTF with genes that have orthologs with analogous functions in soybean and Arabidopsis provide strong circumstantial evidence that these genes are causal for this trait. The three reported loci and candidate genes provide useful targets for marker-assisted breeding in mung beans.
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  • 文章类型: Journal Article
    大米,一种关键的谷类作物,由于其对低温的固有敏感性,应对生产力挑战,主要是在幼苗和孕穗期。认识到水稻冷胁迫信号的多基因复杂性,进行了荟萃分析,关注耐寒的20个生理性状。这一举措允许将242个QTL的遗传数据整合为58个元QTL,从而极大地限制了遗传和物理间隔,84%的meta-QTLs(MQTLs)降至2Mb以下。这些MQTL中的10,505个基因列表,利用表达数据集进一步完善,以查明在冷胁迫期间表现出值得注意的差异调节的46个关键基因。这项研究强调了几种TF的存在,如WRKY,NAC,CBF/DREB,MYB,和bHLH,以它们在寒冷应激反应中的作用而闻名。Further,涉及玉米的正交分析,大麦,拟南芥鉴定出OsWRKY71,作为增强多种作物耐寒性的潜在候选者。总之,我们的研究描绘了复杂的遗传结构支撑水稻耐寒性,并提出了重要的候选基因,为进一步的研究和育种策略提供了重要的见解,重点是加强作物对抗寒冷胁迫,从而增强全球粮食韧性。
    在线版本包含补充材料,可在10.1007/s12298-024-01412-1获得。
    Rice, a critical cereal crop, grapples with productivity challenges due to its inherent sensitivity to low temperatures, primarily during the seedling and booting stages. Recognizing the polygenic complexity of cold stress signaling in rice, a meta-analysis was undertaken, focusing on 20 physiological traits integral to cold tolerance. This initiative allowed the consolidation of genetic data from 242 QTLs into 58 meta-QTLs, thereby significantly constricting the genetic and physical intervals, with 84% of meta-QTLs (MQTLs) being reduced to less than 2 Mb. The list of 10,505 genes within these MQTLs, was further refined utilizing expression datasets to pinpoint 46 pivotal genes exhibiting noteworthy differential regulation during cold stress. The study underscored the presence of several TFs such as WRKY, NAC, CBF/DREB, MYB, and bHLH, known for their roles in cold stress response. Further, ortho-analysis involving maize, barley, and Arabidopsis identified OsWRKY71, among others, as a prospective candidate for enhancing cold tolerance in diverse crop plants. In conclusion, our study delineates the intricate genetic architecture underpinning cold tolerance in rice and propounds significant candidate genes, offering crucial insights for further research and breeding strategies focused on fortifying crops against cold stress, thereby bolstering global food resilience.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s12298-024-01412-1.
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  • 文章类型: Journal Article
    \'念珠菌phytoplasmamelia\'是与中国黄化病有关的病原体,这已成为阿根廷中国林业生产的主要植物检疫问题。尽管有经济影响,这种植物质的基因组信息尚未公布,这阻碍了它在基因组水平上的表征。在这项研究中,我们使用宏基因组学方法分析了Ca的基因组草案。P.Meliae\'菌株ChTYXIII。草案集合由21个重叠群组成,总长度为751.949bp,注释揭示了669个CDS,34个tRNA,和1组rRNA操纵子。代谢途径分析表明,ChTYXIII包含用于糖酵解的完整核心基因和用于蛋白质易位的功能性Sec系统。我们基于133个单拷贝基因和基因组到基因组指标的系统基因组分析支持将其分类为独特的Ca。P.MPV进化枝内的物种。我们还确定了31个推定效应子,包括SAP11的同源物和其他仅在该病原体中描述的同源物。我们的直系同源分析揭示了Ca基因组中的37个PMU核心基因。P.Meliae\'ChTYXIII,导致2个完整的PMU的鉴定。我们的工作为Ca提供了重要的基因组信息。马柳和其他植物为16SrXIII(MPV)组。
    \'Candidatus Phytoplasma meliae\' is a pathogen associated with chinaberry yellowing disease, which has become a major phytosanitary problem for chinaberry forestry production in Argentina. Despite its economic impact, no genome information of this phytoplasma has been published, which has hindered its characterization at the genomic level. In this study, we used a metagenomics approach to analyze the draft genome of the \'Ca. P. meliae\' strain ChTYXIII. The draft assembly consisted of twenty-one contigs with a total length of 751.949 bp, and annotation revealed 669 CDSs, 34 tRNAs, and 1 set of rRNA operons. The metabolic pathways analysis showed that ChTYXIII contains the complete core genes for glycolysis and a functional Sec system for protein translocation. Our phylogenomic analysis based on 133 single-copy genes and genome-to-genome metrics supports the classification as unique \'Ca. P. species\' within the MPV clade. We also identified 31 putative effectors, including a homolog to SAP11 and others that have only been described in this pathogen. Our ortholog analysis revealed 37 PMU core genes in the genome of \'Ca. P. meliae\' ChTYXIII, leading to the identification of 2 intact PMUs. Our work provides important genomic information for \'Ca. P. meliae\' and others phytoplasmas for the 16SrXIII (MPV) group.
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  • 文章类型: Journal Article
    双单倍体(DH)育种是通过加速作物改良来确保全球粮食安全的强大技术。DH可以通过使用单倍体诱导原料(HIS)在植物中产生。玉米中广泛使用的HIS已知由ZmPLA管理,ZmDMP,ZmPLD3和ZmPOD65基因。在水稻和小麦中发展这样的HIS,我们已经使用计算机模拟方法鉴定了这些基因的推定直系同源物。OsPLD1;TaPLD1和OsPOD6;TaPOD8被鉴定为水稻和小麦中ZmPLD3和ZmPOD65的推定直系同源物,分别。尽管与ZmPLD3密切相关,但OsPLD1和TaPLD1显示出更高的花药特异性表达。同样,基于系统发育和表达分析,发现OsPOD6和TaPOD8与ZmPOD65密切相关。然而,与ZmPLD3和ZmPOD65不同,每种作物都发现了两种ZmDMP直向同源物。水稻中的OsDMP1和OsDMP2以及小麦中的TaDMP3和TaDMP13在序列和表达模式上都与ZmDMP相似。此外,玉米DMP蛋白的类似物,这些基因具有四个跨膜螺旋,使得它们最适合被视为ZmDMP直系同源物。通过基于CRISPR/Cas9的基因组编辑修饰这些预测的直系同源基因可以在水稻和小麦中产生高效的HIS。除了揭示单倍体诱导的遗传机制外,HIS的发展将促进这些作物的遗传改良。
    在线版本包含补充材料,可在10.1007/s13205-023-03857-9获得。
    Doubled haploid (DH) breeding is a powerful technique to ensure global food security via accelerated crop improvement. DH can be produced in planta by employing haploid inducer stock (HIS). Widely used HIS in maize is known to be governed by ZmPLA, ZmDMP, ZmPLD3, and ZmPOD65 genes. To develop such HIS in rice and wheat, we have identified putative orthologs of these genes using in silico approaches. The OsPLD1; TaPLD1, and OsPOD6; TaPOD8 were identified as putative orthologs of ZmPLD3 and ZmPOD65 in rice and wheat, respectively. Despite being closely related to ZmPLD3, OsPLD1 and TaPLD1 have shown higher anther-specific expression. Similarly, OsPOD6 and TaPOD8 were found closely related to the ZmPOD65 based on both phylogenetic and expression analysis. However, unlike ZmPLD3 and ZmPOD65, two ZmDMP orthologs have been found for each crop. OsDMP1 and OsDMP2 in rice and TaDMP3 and TaDMP13 in wheat have shown similarity to ZmDMP in terms of both sequence and expression pattern. Furthermore, analogs to maize DMP proteins, these genes possess four transmembrane helices making them best suited to be regarded as ZmDMP orthologs. Modifying these predicted orthologous genes by CRISPR/Cas9-based genome editing can produce a highly efficient HIS in both rice and wheat. Besides revealing the genetic mechanism of haploid induction, the development of HIS would advance the genetic improvement of these crops.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s13205-023-03857-9.
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  • 文章类型: Journal Article
    导致重度抑郁症(MDD)表现异质性的潜在生物学机制仍然知之甚少。强调需要一个概念框架来解释这种变异性,并弥合动物模型和临床终点之间的差距。这里,我们假设对来自不同慢性应激实验系统的分子数据进行比较分析,MDD有可能深入了解这些机制并解决这一差距。因此,我们比较了死后MDD受试者和暴露于慢性可变应激(CVS)的小鼠脑组织的转录组学谱,以鉴定直系同源基因.核糖体蛋白基因(RPG)下调,在两种情况下,相关核糖体蛋白(RP)假基因均上调。使用MDD和CVS组之间常见的改变的RPG进行的种子基因共表达分析显示,下调的RPG通过RP-假基因驱动机制稳态地调节了两组的突触变化。体外分析表明RPG失调是糖皮质激素驱动的对应激的内分泌反应。计算机模拟分析进一步表明,在从MDD缓解期间,失调被逆转,并选择性地响应氯胺酮,而不是丙咪嗪。这项研究提供了第一个证据,表明应激过程中的核糖体失调是人类MDD和慢性应激暴露小鼠的保守表型。我们的结果为以下假设奠定了基础:压力诱导的RPG和,因此,核糖体有助于MDD和慢性压力相关情绪障碍的突触失调。我们讨论了核糖体异质性在抑郁症和其他情绪障碍的各种表现中的作用。
    The underlying biological mechanisms that contribute to the heterogeneity of major depressive disorder (MDD) presentation remain poorly understood, highlighting the need for a conceptual framework that can explain this variability and bridge the gap between animal models and clinical endpoints. Here, we hypothesize that comparative analysis of molecular data from different experimental systems of chronic stress, and MDD has the potential to provide insight into these mechanisms and address this gap. Thus, we compared transcriptomic profiles of brain tissue from postmortem MDD subjects and from mice exposed to chronic variable stress (CVS) to identify orthologous genes. Ribosomal protein genes (RPGs) were down-regulated, and associated ribosomal protein (RP) pseudogenes were up-regulated in both conditions. A seeded gene co-expression analysis using altered RPGs common between the MDD and CVS groups revealed that down-regulated RPGs homeostatically regulated the synaptic changes in both groups through a RP-pseudogene-driven mechanism. In vitro analysis demonstrated that the RPG dysregulation was a glucocorticoid-driven endocrine response to stress. In silico analysis further demonstrated that the dysregulation was reversed during remission from MDD and selectively responded to ketamine but not to imipramine. This study provides the first evidence that ribosomal dysregulation during stress is a conserved phenotype in human MDD and chronic stress-exposed mouse. Our results establish a foundation for the hypothesis that stress-induced alterations in RPGs and, consequently, ribosomes contribute to the synaptic dysregulation underlying MDD and chronic stress-related mood disorders. We discuss the role of ribosomal heterogeneity in the variable presentations of depression and other mood disorders.
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