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近日节律是生物节律中最重要的一种。它是一种以近似24 h为周期的自主振荡器,普遍存在于生物界中。近日节律主要受生物钟基因的调控,在哺乳动物中已发现时钟基因(Clock)、周期基因(Period,Per)家族、隐花色素基因(Cryptochrome1,Cry)家族、Bmal1(Brain and muscle ARNT-like 1)在内的多种重要的生物钟基因。这些基因及其蛋白质产物构成的反馈调节环是生物钟运行的分子基础。研究表明,生物钟基因不仅仅在近日节律的中枢系统中存在表达,在外周组织中也存在表达。而且生物钟基因与哺乳动物生殖密切相关,提示可能在生殖领域中具有重要的调控作用。主要从几个关键生物钟基因的发现、在近日节律和非近日节律中的调节作用、以及与哺乳动物生殖的关系做一综述。 相似文献
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生物钟现象是一种普遍存在于生物界细胞的内源节律性保持机制。生物钟机制的存在可以使生物体的代谢行为产生并维持以24 h为周期的昼夜节律,从而更好地适应于地球自转所产生的环境条件昼夜间节律性变化。蓝藻是目前生物钟分子机制研究中的模式生物,其依赖于k ai基因家族成员的核心生物钟调控模式已经被众多研究者详细阐明。蓝藻生物钟的核心振荡器是由蓝藻k aiA/B/C的编码产物来调控的,Kai蛋白的表达模式具有节律性。KaiC蛋白磷酸化状态的节律性循环及输入、输出途径相关组成蛋白的翻译后修饰状态节律性循环共同组成其反馈回路,负责维持生物钟节律性振荡的持续进行并与环境周期保持同步。传统的蓝藻生物钟分子机制模型认为,节律性表达基因翻译产物的转录/翻译负反馈抑制环是生物节律性维持和输出的关键。遗憾的是,在其它物种生物钟分子机制研究中未发现由kai基因家族成员同源基因组成的节律性标签,这表明以k aiA/B/C为核心振荡器的生物钟系统并不是一种跨物种保守的生物钟系统。近期,人们发现非转录/翻译依赖的振荡器(NTO)也具有成为生物节律性产生和维持的“源动力”的可能。过氧化物氧化还原酶(PRX)氧化还原状态节律性是第一种被报道的跨物种保守的NTO节律性标签,这也日渐成为蓝藻生物钟分子机制研究新的热点。 相似文献
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生物钟对生物机体的生存与环境适应具有着重要意义,其相关研究近年来受到人们的广泛关注。生物钟的重要性质之一是内源节律的周期性,当前的研究认为这种周期性是由生物钟相关基因转录翻译的多反馈环路构成核心机制调控着近似24 h的节律振荡。哺乳动物的生物钟系统存在一个多层次的结构,包括位于视交叉上核的主时钟和外周器官和组织的子时钟。虽然主时钟和子时钟存在的组织不同,但是参与调节生物钟的分子机制是一致的。近年来,通过正向、反向遗传学方法和表观遗传学的研究方法,对生物钟的分子机制的解析和认知愈发深入。本文在简单回顾生物钟基因发现历史的基础上,重点从遗传学和表观遗传学两个方面,从振荡周期的角度,对哺乳动物生物钟分子机制的研究进展进行了综述性介绍,以期为靶向调节生物钟来改善机体的稳态系统的研究提供参考,同时希望能促进时间生物学领域与更多其他领域形成交叉研究。 相似文献
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《生理学报》2021,(5)
生物钟(circadian clock)是机体内在的自主性计时系统,包括视交叉上核(suprachiasmatic nucleus, SCN)中枢生物钟与各组织外周生物钟。分子生物钟的核心机制包括CLOCK/BMAL1二聚体诱导抑制因子CRYs和PERs的转录,CRYs/PERs复合物反馈抑制前者转录活性,进而使这些生物钟核心因子以及节律输出基因的转录水平呈24 h振荡的反馈调节核心环路,以及REV-ERBα和RORα调控BMAL1转录的补充环路。机体大约80%的蛋白编码基因表达呈现明显的昼夜节律性特征,生物钟系统使生物能够适应地球自转所产生的昼夜节律(近日节律),使机体的代谢平衡与能量相互协同。生物钟与代谢稳态相互依存、互为基础,使机体能够高效利用能量,协同机体不同组织,快速适应内外环境变化。肝脏作为机体代谢的中枢器官,其进行的各种生理活动几乎都受到生物钟的控制。生物钟与肝脏代谢调控之间存在多重交互调控机制,两者的交互平衡失调是代谢性疾病的高风险因素。本文主要就肝脏的糖、脂和蛋白质代谢的节律性调控进行了综述,并强调了线粒体功能的振荡,讨论了肝脏代谢对生物钟的反馈调节,并对生物钟研究方法和应用进行展望。 相似文献
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昆虫钟基因研究进展 总被引:1,自引:0,他引:1
昆虫进化形成了内在的生物钟机制以协调行为、生理及代谢节律与外部环境信号同步,从而更有效地利用资源并获得适应性优势。行为、生理及代谢昼夜调控的协调对于昆虫有效应对可预见的生理上的挑战至关重要。生化过程和代谢变化与外部环境的昼夜节律同步性受基因表达的控制,钟基因在昆虫的重要生理过程如中枢及外围生物钟机制、光周期信号传导、光周期介导的外围组织调控、代谢以及免疫中发挥着重要作用。根据信号转导过程中的作用,昆虫钟基因分为3类——信号输入基因、信号震荡起搏器和信号输出基因,它们通过相互作用形成了复杂的转录-翻译反馈回路并参与调控昆虫昼夜节律和光周期事件。本文针对昆虫钟基因的鉴定、分类和功能,作用分子机制以及研究方法和挑战等方面作了总结,并展望了昆虫钟基因未来的研究方向,这将为昆虫钟基因的进一步功能研究及开发利用提供信息参考。 相似文献
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Progress in unravelling the cellular and molecular basis of mammalian circadian regulation over the past decade has provided us with new avenues through which we can explore central nervous system disease. Deteriorations in measurable circadian output parameters, such as sleep/wake deficits and dysregulation of circulating hormone levels, are common features of most central nervous system disorders. At the core of the mammalian circadian system is a complex of molecular oscillations within the hypothalamic suprachiasmatic nucleus. These oscillations are modifiable by afferent signals from the environment, and integrated signals are subsequently conveyed to remote central neural circuits where specific output rhythms are regulated. Mutations in circadian genes in mice can disturb both molecular oscillations and measurable output rhythms. Moreover, systematic analysis of these mutants indicates that they can express an array of abnormal behavioural phenotypes that are intermediate signatures of central nervous system disorders. Furthermore, the response of these mutants to psychoactive drugs suggests that clock genes can modify a number of the brain’s critical neurotransmitter systems. This evidence has led to promising investigations into clock gene polymorphisms in psychiatric disease. Preliminary indications favour the systematic investigation of the contribution of circadian genes to central nervous system disease. 相似文献
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Más P 《Trends in cell biology》2008,18(6):273-281
The past decade has seen a remarkable advance in our understanding of the plant circadian system, mostly in Arabidopsis thaliana. It is now well established that Arabidopsis clock genes and their protein products operate through autoregulatory feedback loops that promote rhythmic oscillations in cellular, metabolic and physiological activities. This article reviews recent studies that have provided evidence for new mechanisms of clock organization and function. These mechanisms include protein-protein interactions and the regulation of protein stability, which, together, directly connect light signalling to the Arabidopsis circadian system. Evidence of rhythmic changes in chromatin structure has also opened new and exciting ways for regulation of clock gene expression. All of these mechanisms ensure an appropriate synchronization with the environment, which is crucial for successful plant growth and development. 相似文献
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果蝇昼夜节律的分子机制研究进展 总被引:6,自引:1,他引:5
果蝇由于遗传易操作性而成为一个研究昼夜节律分子机制的理想模式生物 . 到目前为止,通过遗传学和生物化学方法已经鉴定到 10 多个时钟基因 (clock genes) 和许多时钟相关基因,包括时钟输入基因和钟控基因 . 这些时钟基因以及它们的相应产物组成两个互相依赖的转录 / 翻译反馈环路,从而调节行为和生理的昼夜节律 . 果蝇这种核心钟的工作原理同样见于哺乳动物 . 相似文献
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Werner R 《Chronobiology international》2002,19(2):325-343
Chlamydomonas reinhardtii has been used as an experimental model organism for circadian rhythm research for more than 30 yr. Some of the physiological rhythms of this alga are well established, and several clock mutants have been isolated. The cloning of clock genes from these mutant strains by positional cloning is under way and should give new insights into the mechanism of the circadian clock. In a spectacular space experiment, the question of the existence of an endogenous clock vs. an exogenous mechanism has been studied in this organism. With the emergence of molecular analysis of circadian rhythms in plants in 1985, a circadian gene expression pattern of several nuclear and chloroplast genes was detected. Evidence is now accumulating that shows circadian control at the translational level. In addition, the gating of the cell cycle by the circadian clock has been analyzed. This review focuses on the different aspects of circadian rhythm research in C. reinhardtii over the past 30 yr. The suitability of Chlamydomonas as a model system in chronobiology research and the adaptive significance of the observed rhythms will be discussed. 相似文献
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Diapause is an adaptive response triggered by seasonal photoperiodicity to overcome unfavorable seasons. The photoperiodic clock is a system that controls seasonal physiological processes, but our knowledge about its physiological mechanisms and genetic architecture remains incomplete. The circadian clock is another system that controls daily rhythmic physiological phenomena. It has been argued that there is a connection between the two clocks. To examine the genetic connection between them, we analyzed the associations of five circadian clock genes (period, timeless, Clock, cycle and cryptochrome) with the occurrence of diapause in Drosophila triauraria, which shows a robust reproductive diapause with clear photoperiodicity. Non-diapause strains found in low latitudes were compared in genetic crosses with the diapause strain, in which the diapause trait is clearly dominant. Single nucleotide polymorphism and deletion analyses of the five circadian clock genes in backcross progeny revealed that allelic differences in timeless and cryptochrome between the strains were additively associated with the differences in the incidence of diapause. This suggests that there is a molecular link between certain circadian clock genes and the occurrence of diapause. 相似文献
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《Chronobiology international》2013,30(2):325-343
Chlamydomonas reinhardtii has been used as an experimental model organism for circadian rhythm research for more than 30 yr. Some of the physiological rhythms of this alga are well established, and several clock mutants have been isolated. The cloning of clock genes from these mutant strains by positional cloning is under way and should give new insights into the mechanism of the circadian clock. In a spectacular space experiment, the question of the existence of an endogenous clock vs. an exogenous mechanism has been studied in this organism. With the emergence of molecular analysis of circadian rhythms in plants in 1985, a circadian gene expression pattern of several nuclear and chloroplast genes was detected. Evidence is now accumulating that shows circadian control at the translational level. In addition, the gating of the cell cycle by the circadian clock has been analyzed. This review focuses on the different aspects of circadian rhythm research in C. reinhardtii over the past 30 yr. The suitability of Chlamydomonas as a model system in chronobiology research and the adaptive significance of the observed rhythms will be discussed. 相似文献
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Neurospora crassa has been a model organism for the study of circadian clocks for the past four decades. Among natural accessions of Neurospora crassa, there is significant variation in clock phenotypes. In an attempt to investigate natural allelic variants contributing to quantitative variation, we used a quantitative trait loci mapping approach to analyze three independent mapping populations whose progenitors were collected from geographically isolated locations. Two circadian clock phenotypes, free-running period and entrained phase, were evaluated in the 188 F(1) progeny of each mapping population. To identify the clock QTL, we applied two QTL mapping analyses: composite interval mapping (CIM) and Bayesian multiple QTL analysis (BMQ). When controlling false positive rates < or =0.05, BMQ appears to be the more sensitive of the two approaches. BMQ confirmed most of the QTL from CIM (18 QTL) and identified 23 additional QTL. While 13 QTL colocalize with previously identified clock genes, we identified 30 QTL that were not linked with any previously characterized clock genes. These are candidate regions where clock genes may be located and are expected to lead to new insights in clock regulation. 相似文献