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【Nature】《自然》：科学家发现独立于基因的生
这种机制的驱动力可能来自新陈代谢机制本身
生物钟控制着生命活动的内在节律，过去人们一直认为它的“驱动齿轮”是基因。而英国研究人员在新一期《自然》杂志上报告说，他们发现了独立于基因的生物钟机制，这种与新陈代谢有关的机制构成了生物钟的“第二齿轮”。
英国剑桥大学研究人员报告说，首次发现人类血液红细胞中也存在生物钟。与其他细胞拥有脱氧核糖核酸（DNA）等遗传物质不同，红细胞中没有DNA，因此它不会像过去认为的那样，根据基因发出的信号来调整活动节律。研究人员探测发现，红细胞中一种名为peroxiredoxin的抗氧化蛋白的含量会出现24小时的周期性起落，这说明有另一种生物钟机制在起作用。
英国爱丁堡大学等机构的研究人员在同期《自然》杂志上发表另一份研究报告说，他们在海藻中也发现了类似现象。虽然海藻细胞中有DNA等遗传物质，但在黑暗环境中其DNA不会作为生物钟的“驱动齿轮”而转动。研究人员在黑暗环境中也探测到海藻细胞中同一种抗氧化蛋白的含量有周期性起落现象。
这两项研究说明，除了基因以外，还存在驱动生物钟运行的“第二齿轮”。由于这种抗氧化蛋白在细胞新陈代谢中扮演着重要角色，研究人员认为“第二齿轮”的驱动力应该来自新陈代谢机制本身。
爱丁堡大学的安德鲁·米勒教授说，海藻是一种极为古老的生物，因此这种与新陈代谢有关的生物钟机制很可能已经存在数十亿年之久，并在进化中成为人类等生物体内普遍存在的现象。这一发现还说明生物钟比人们以前所知更精密、更复杂，需要更多深入研究。
此前研究发现，如果生物钟因坐飞机、上夜班等原因被扰乱，常会引起新陈代谢紊乱和不舒服，甚至有可能导致糖尿病等疾病，本次研究进展将有助于相关领域的进一步探索。 Circadian (~24 hour) clocks are fundamentally important for coordinated physiology in organisms as diverse as cyanobacteria and humans. All current models of the molecular circadian clockwork in eukaryotic cells are based on transcription–translation feedback loops. Non-transcriptional mechanisms in the clockwork have been difficult to study in mammalian systems. We circumvented these problems by developing novel assays using human red blood cells, which have no nucleus (or DNA) and therefore cannot perform transcription. Our results show that transcription is not required for circadian oscillations in humans, and that non-transcriptional events seem to be sufficient to sustain cellular circadian rhythms. Using red blood cells, we found that peroxiredoxins, highly conserved antioxidant proteins, undergo ~24-hour redox cycles, which persist for many days under constant conditions (that is, in the absence of external cues). Moreover, these rhythms are entrainable (that is, tunable by environmental stimuli) and temperature-compensated, both key features of circadian rhythms. We anticipate that our findings will facilitate more sophisticated cellular clock models, highlighting the interdependency of transcriptional and non-transcriptional oscillations in potentially all eukaryotic cells.
http://www.nature.com/nature/journal/v469/n7331/abs/nature09702.html
Circadian rhythms are ubiquitous in eukaryotes, and coordinate numerous aspects of behaviour, physiology and metabolism, from sleep/wake cycles in mammals to growth and photosynthesis in plants1, 2. This daily timekeeping is thought to be driven by transcriptional–translational feedback loops, whereby rhythmic expression of ‘clock’ gene products regulates the expression of associated genes in approximately 24-hour cycles. The specific transcriptional components differ between phylogenetic kingdoms3. The unicellular pico-eukaryotic alga Ostreococcus tauri possesses a naturally minimized clock, which includes many features that are shared with plants, such as a central negative feedback loop that involves the morning-expressed CCA1 and evening-expressed TOC1 genes4. Given that recent observations in animals and plants have revealed prominent post-translational contributions to timekeeping5, a reappraisal of the transcriptional contribution to oscillator function is overdue. Here we show that non-transcriptional mechanisms are sufficient to sustain circadian timekeeping in the eukaryotic lineage, although they normally function in conjunction with transcriptional components. We identify oxidation of peroxiredoxin proteins as a transcription-independent rhythmic biomarker, which is also rhythmic in mammals6. Moreover we show that pharmacological modulators of the mammalian clock mechanism have the same effects on rhythms in Ostreococcus. Post-translational mechanisms, and at least one rhythmic marker, seem to be better conserved than transcriptional clock regulators. It is plausible that the oldest oscillator components are non-transcriptional in nature, as in cyanobacteria7, and are conserved across kingdoms.
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作者:admin@医学,生命科学 2011-01-28 13:02
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