生物钟的基因调控

从细菌到哺乳动物的大多数生物都存在分子时钟,也就是生物钟。它的存在使生物的生理,生化,行为表现出以24小时为周期的节律性。本文从基因组成以及节律发生的分子机制等方面,对昼夜节街生物钟进行综述。     

Timeless与生物钟基因

综述了timeless基因的发现、多态性和重要功能。timeless是最先被发现的两个生物钟基因之一。生物钟的昼夜节律由PER、TIM、CLOCK和CYCLE4个生物钟齿轮组成的正负反馈回路进行调节。其中TIM可以受光因子调控,它还可以与PER形成异二聚体,通过正负调控方式调节果蝇的昼夜节律行为。     

生物钟的分子机制研究进展

RecentDevelopmentsinMolecularMechanismsofBiologicalClockHouBingkai(DepartmentofBiology,ShandongUniversity,Jinan250100)YuHuimin(DepartmentofBiochemistry,ShandongEducationCollege,Jinan250013)生物的昼夜节奏表现,从单细胞生物到多细胞生物,从原校生物到真核生物都曾被描述过。由于这种现象在生物界广泛存在,关于它的特征、意义和机理的研究日益受到人们重视。其中最重要和最吸引人的方面是它的测时系统—一生物钟（biologicalclock）,也称生物振荡器（oscillators）。近年来,人们从分子水平对生物钟的研究比较活…     

生物钟基因3及其表达的调节机制

众所周知 ,生物体的新陈代谢过程 ,细胞和细胞器官的生理功能 ,以及心理行为等生命活动往往随着昼夜循环而发生规律性的变化。就是在实验室恒定的条件下 ,消除一切环境因子的影响 ,生命活动仍表现出昼夜节律性的变化。这说明昼夜节律受体内的测时系统——生物钟的控制。从 5 0年代至今 ,人们对生物的昼夜节律及其调控机制进行了深入地研究 ,特别是应用生物化学和分子生物学的方法 ,使人们逐步了解了生物节律的特点 ,生物钟基因及其表达的调控机制。1　生物钟基因存在于不同生物体中的昼夜节律时钟都表现出 3个共同的特点 :1 )在恒定的环境条…     

生物钟基因研究进展

昼夜节律是以大约24 h为周期波动的生物现象.这些节律包括血压、体温、激素水平、血中免疫细胞的数量、睡眠觉醒周期循环等.基因水平上的昼夜节律研究还只是刚起步,介绍不同物种控制昼夜行为的共同基因(如period 、timless 、clock基因等)的研究进展,特别是一些有关调控昼夜节律基因的转录因子的研究.同时讨论果蝇和人类生物钟调节的共同分子机制.     

生物钟基因与脂质代谢紊乱

生物钟是生物适应环境节律变化形成的特殊生理机制,具有一定的节律性。生物钟基因被证实参与调节多种生物生理活动,如生物的各种代谢活动、细胞的凋亡与坏死、肿瘤的发生与发展和炎症反应等。其中,脂质代谢作为一项重要的代谢活动,其紊乱可能诱发高血脂症、动脉粥样硬化等疾病。脂质代谢的调节受生物钟相关基因的调节。本文就有关生物钟的生理机制及生物钟基因参与脂质代谢调节的研究进行综述。     

动物昼夜生物钟的分子机制

动物的昼夜生物钟是一种十分重要的生物节律,对生物对环境的适应有着重要的意义。昼夜节律是一种综合适应,它体现在个体、器官、组织等不同的水平上。最近20几年来．人们通过对果蝇和鼠的昼夜生物钟振荡子的研究,逐渐揭示了动物生物钟的负反馈回路的分子机制。     

生物节律基因period3的研究进展

昼夜节律是所有真核生物和部分原核生物的基本特征,一组节律表达的生物钟基因形成24 h周期振荡的自主调节转录-翻译反馈回路。period（per）基因家族是生物钟反馈回路中重要组成成分,per3基因是period基因家族成员之一。人类的per3基因定位于染色体1p36,其编码区第18外显子中含有一个灵长类特有的串联重复序列（variable number tandem repeat,VNTR）。该VNTR包含一簇理论上的磷酸化位点,能影响PER3蛋白的磷酸化降解,影响PER3蛋白的功能。近年研究发现,per3基因多态性与睡眠结构、睡眠紊乱发病年龄、睡眠剥夺后次日清晨执行能力等密切相关。     

生物钟基因与哺乳动物生殖

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。     

家蚕昼夜节律生物钟基因的生物信息学分析

: 昼夜节律是最普遍的生物节律现象,受遗传基因调控,其分子机制在黑腹果蝇Drosophila melanogaster中有较为深入的研究,在其他昆虫中的研究相对较少。家蚕Bombyx mori的滞育是对昼夜节律授时因子响应的一种现象,可作为研究的参照。通过电子克隆的方法获得了家蚕生物钟基因Bmvri,Bmcyc,Bmtim2,Bmpdp完整的开放阅读框(ORF)序列,以及Bmclk基因的ORF片段,并对上述基因及其表达产物进行了结构分析、染色体定位和系统的分子进化分析,根据这些基因及其表达产物的结构特征结合现有的数据资源,整合了家蚕昼夜节律生物钟反馈环路。     

华北大黑鳃金龟生物钟基因HoPer的克隆和表达模式分析

为明确华北大黑鳃金龟Holotrichia oblita周期蛋白基因（Period, Per）的表达模式,本研究采用RACE技术从2龄幼虫中克隆到生物钟基因HoPer,并进行生物信息学分析;再采用RT-qPCR技术检测HoPer在不同发育阶段、雌雄成虫不同组织以及不同光周期下的表达水平。结果表明：HoPer编码1 172个氨基酸,蛋白分子量129.67 kDa,等电点为5.62。HoPer推导出的氨基酸序列中具有2个PAS和1个Period C结构域,是昆虫PER蛋白的典型结构特征。表达模式分析得出：HoPer在各个发育阶段均有表达,但在卵中的表达量显著高于其他发育时期;HoPer在雌雄成虫的头和触角中表达水平最高,其次为翅和足,在胸和腹中表达水平最低;雌雄成虫中HoPer在试验设定的5个光周期中未发现明显的表达差异。本研究为进一步阐明华北大黑鳃金龟HoPer基因功能以及其在生物钟网络中的调控作用提供了一定的参考。     

A role for copper in biological time-keeping

A family of cell surface and growth related proteins that oxidize both NADH and hydroquinones and carry out protein disulfide-thiol interchange (ECTO-NOX proteins) exhibits unique characteristics. The two activities they catalyze, hydroquinone or NADH oxidation and protein disulfide-thiol interchange, alternate in CNOX (the constitutive ECTO-NOX), to generate a regular period length of 24 min. For NADH or hydroquinone oxidation each period is defined by maxima that recur at intervals of 24 min. Here, we report that bound Cu^II is required to sustain the 24 min oscillation cycle of CNOX. CNOX preparations from plasma membranes of soybean, when unfolded in the presence of the copper chelator bathocuproine and refolded, lose activity. When refolded in the presence of copper, activity is restored. Unexpectedly, however, the released copper is capable of catalyzing NADH (or hydroquinone) oxidation in the absence of protein. Solvated Cu^II as the chloride or other salts alone is capable of catalyzing NADH oxidation and the oxidation rates oscillate with an overall period length of 24 min. With Cu^IICl₂ the pattern consists of five maxima, two of which are separated by an interval of 6 min and three of which are separated by intervals of 4.5 min [6 min + 4 (4.5 min)]. The period length is independent of temperature and pH. The asymmetry of the oscillatory pattern is retained after solvation of the Cu^II salts in D₂O but the overall period length is increased to 30 min. The findings suggest that the bound copper of CNOX and perhaps of ECTO-NOX proteins in general, is essential to maintain the structural changes that underlie the periodic alternations in activity that define the 24 min time-keeping cycle of the protein.     

Independence of genetic variation between circadian rhythm and development time in the seed beetle, Callosobruchus chinensis

A positive genetic correlation between periods of circadian rhythm and developmental time supports the hypothesis that circadian clocks are implicated in the timing of development. Empirical evidence for this genetic correlation in insects has been documented in two fly species. In contrast, here we show that there is no evidence of genetic correlation between circadian rhythm and development time in the adzuki bean beetle, Callosobruchus chinensis. This species has variation that is explained by a major gene in the expression and period length of circadian rhythm between strains. In this study, we found genetic variation in development time between the strains. The development time was not covaried with either the incidence or the period length of circadian rhythm among the strains. Crosses between strains suggest that development time is controlled by a polygene. In the F₂ individuals from the crosses, the circadian rhythm is attributable to allelic variation in the major gene. Across the F₂ individuals, development time was not correlated with either the expression or the period length of circadian rhythm. Thus, we found no effects of major genes responsible for variation in the circadian rhythm on development time in C. chinensis. Our findings collectively give no support to the hypothesis that the circadian clock is involved in the regulation of development time in this species.     

Daily rhythms after vaccination on specific and non-specific responses in Nile tilapia (Oreochromis niloticus)

ABSTRACT

We evaluated the daily changes in immunological and hematological factors in tilapia (Oreochromis niloticus) after an immunization period with a subsequent challenge. Experiments were divided into two phases: Phase 1 (immunization): 144 fish were distributed into two groups with 72 fish in six tanks. One group (T1) was immunized, comprising six vaccination time points (ZT schedule = ZT2 h, ZT6 h, ZT10 h, ZT14 h, ZT18 h, ZT22 h). The same schedule was applied to the other group, but with saline solution (non-vaccinated: T2). Both groups remained in the laboratory for 30 days (considered the immunization period). Phase 2 (challenge): on day 30, both vaccinated and non-vaccinated groups were challenged with Streptococcus agalactiae (2.0 × 10⁷ CFU mL^?1) following the same ZT schedule to stimulate the immune response without leading to widespread infection and mortality. On day 45, blood and head kidney samples were collected during the same ZT schedule. The variations in time of the following parameters within each group were evaluated: hematology, peroxidase activity, IgM, tnf-α3, tgf-β1, il-1β and il-12 gene expression. No significant mortality was observed for the groups or the ZT schedule (p > 0.05). Daily rhythms with diurnal acrophases were found in T2 for il12, tnf-α3 and tgf-β1 expression gene, while the acrophases of the peroxidase level, hematocrit and thrombocytes were at nighttime (p < 0.05). In contrast, most of the parameters in the vaccinated tilapia showed no daily rhythms (p > 0.05), except IgM. For all the parameters, the interaction effect between time and treatment (vaccinated and non-vaccinated groups) depended on ZT. Our results reveal that the humoral and non-specific immune system displayed a circadian rhythm based on the light-dark cycle, which could be affected by the vaccination procedure in tilapia.     

Review of the Dual-Clock Control of Tidal Rhythms and the Hypothesis that the Same Clock Governs Both Circatidal and Circadian Rhythms

Discoveries first published in 1986 did not fit the de rigueur working hypothesis that the clocks governing tide-associated rhythms had a fundamental period of 12.4 h, a value equal to the average interval between successive tides on most coastlines of the world. To explain the results a dual-clock schema was fashioned that envisioned two clocks, strongly coupled together 180° antiphase, each running at a basic rate of 24.8 h (the interval of a lunar day), as the driving agents of tide-associated rhythms (details are given in the text). This elaboration has been named the circalunidian-clock hypothesis, a hypocorism used in some armchair ruminations back in 1973. In the decade since 1986, a goodly amount of evidence has been garnered that is consistent with this hypothesis—suggesting that first-call divination appears to have been visionary. Acceptance of this hypothesis leads to further cerebration that a 24.8-h clock, its circa periods in constant conditions, and other properties—which fully overlap with our perception of the circadian clock that drives daily rhythms—may indicate that circadian and circalunidan timepieces are not different entities. The known properties of both daily and lunar clock-types are compared and contrasted, and, with the exception of one feature (for which there is at least a philosophical explanation), it is concluded that the same clock that drives tidal rhythms could also motor daily rhythms, i.e., there may be no such thing as a 12.4-h horologue.     

Review of the Dual-Clock Control of Tidal Rhythms and the Hypothesis that the Same Clock Governs Both Circatidal and Circadian Rhythms

Discoveries first published in 1986 did not fit the de rigueur working hypothesis that the clocks governing tide-associated rhythms had a fundamental period of 12.4 h, a value equal to the average interval between successive tides on most coastlines of the world. To explain the results a dual-clock schema was fashioned that envisioned two clocks, strongly coupled together 180° antiphase, each running at a basic rate of 24.8 h (the interval of a lunar day), as the driving agents of tide-associated rhythms (details are given in the text). This elaboration has been named the circalunidian-clock hypothesis, a hypocorism used in some armchair ruminations back in 1973. In the decade since 1986, a goodly amount of evidence has been garnered that is consistent with this hypothesis—suggesting that first-call divination appears to have been visionary. Acceptance of this hypothesis leads to further cerebration that a 24.8-h clock, its circa periods in constant conditions, and other properties—which fully overlap with our perception of the circadian clock that drives daily rhythms—may indicate that circadian and circalunidan timepieces are not different entities. The known properties of both daily and lunar clock-types are compared and contrasted, and, with the exception of one feature (for which there is at least a philosophical explanation), it is concluded that the same clock that drives tidal rhythms could also motor daily rhythms, i.e., there may be no such thing as a 12.4-h horologue.