Biophysical clocks face a trade-off between internal and external noise resistance.
Biophysical clocks face a trade-off between internal and external noise resistance.
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DOI：
10.7554/elife.37624
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发表时间：
2018-07-10
期刊：
影响因子：
7.7
通讯作者：
Murugan A
中科院分区：
文献类型：
--
作者：
Pittayakanchit W;Lu Z;Chew J;Rust MJ;Murugan A
许多生物利用自由运行的生物钟来预测昼夜循环。然而，其他生物体使用简单的刺激反应策略（“沙漏时钟”），目前还不清楚这种策略何时足以甚至优于自由运行的时钟。在这里，我们发现，自由运行的时钟，如在蓝细菌Synechococcus elongatus和人类中发现的时钟，可以有效地投影出由于天气模式（“外部噪声”）的光强度波动，通过利用其极限环吸引子。然而，这种极限环必然容易受到“内部噪声”的影响。因此，在足够高的内部噪声，点吸引子为基础的“沙漏”时钟，如那些发现在一个较小的蓝藻与低蛋白质拷贝数，原绿球藻，可以胜过自由运行的时钟。通过在这两个制度之间的插值在不同范围的振荡器从整个生物学，我们展示了生化时钟架构，最适合不同的相对强度的外部和内部噪声。太阳每天的升起和落下也许是地球上最可预测的模式。许多生物，从古老的细菌到动物和植物，已经进化出内部生物钟来预测特定的事件，如黄昏和黎明。然而，生物钟也需要在面临不规则时继续工作-无论是来自有机体内部还是来自外部因素，例如使天空变暗的经过的云。包括人类在内的一些生物体有一个所谓的“自由运行”的时钟，可以产生24小时的节奏，即使没有任何时间触发器也会继续滴答作响。其他的，如某些蓝藻，有一个“沙漏”的时钟，不是自我维持的-相反，这些时钟显示一个简单的反应，日出（或日落），将逐渐死亡没有另一个日落（或日出）。到目前为止，还不清楚为什么生物体有不同种类的时钟，以及是否一种类型的时钟比其他类型的时钟更适合某些条件。在这里，Pittayakanchit，Lu等人分析和比较了各种生物体中时钟的数学模型，从蓝藻和真菌到植物和动物。结果表明，内部和外部的不规则性对生物钟产生了相反的压力。自由运行的时钟更精确，对外部波动更鲁棒，但更容易受到内部波动的影响。相比之下，沙漏时钟可以保持准确的内部不规则性高，但可以被外部的干扰。生物钟影响整个生物体的健康，错误的时钟与许多疾病有关。Pittayakanchit，Lu等人的研究表明，生物钟的最佳结构取决于生物体外部和内部环境中不规则性的平衡。下一步将是了解生物体是否可以在环境变化时改变其时钟结构。更好地了解生物钟是如何调节的，可能有助于我们找到调整错误时钟的方法，以适应外部环境和有机体的内部状态。
Many organisms use free running circadian clocks to anticipate the day night cycle. However, others organisms use simple stimulus-response strategies (‘hourglass clocks’) and it is not clear when such strategies are sufficient or even preferable to free running clocks. Here, we find that free running clocks, such as those found in the cyanobacterium Synechococcus elongatus and humans, can efficiently project out light intensity fluctuations due to weather patterns (‘external noise’) by exploiting their limit cycle attractor. However, such limit cycles are necessarily vulnerable to ‘internal noise’. Hence, at sufficiently high internal noise, point attractor-based ‘hourglass’ clocks, such as those found in a smaller cyanobacterium with low protein copy number, Prochlorococcus marinus, can outperform free running clocks. By interpolating between these two regimes in a diverse range of oscillators drawn from across biology, we demonstrate biochemical clock architectures that are best suited to different relative strengths of external and internal noise. The daily rising and setting of the sun is perhaps the most predictable pattern on Earth. Many organisms, from ancient bacteria to animals and plants, have evolved internal biological clocks to anticipate specific events such as dusk and dawn. However, biological clocks also need to continue working when faced with irregularities – both arising from within the organism and from external factors, such as a passing cloud that darkens the sky. Some organisms, including humans, have a so-called ‘free-running’ clock that generates a 24-hour rhythm, and keeps ticking even in the absence of any time triggers. Others, such as certain cyanobacteria, have an ‘hourglass’ clock that is not self-sustained – rather, these clocks show a simple response to the sunrise (or sunset) that would gradually perish without another sunset (or sunrise). So far, it has been unclear why organisms have different kinds of clocks and if one type of clock is better suited for some conditions than others. Here, Pittayakanchit, Lu et al. analyzed and compared mathematical models of clocks in a variety of organisms, from cyanobacteria and fungi to plants and animals. The results revealed that internal and external irregularities put opposing pressures on biological clocks. Free-running clocks are more precise and more robust to external fluctuations, but more susceptible to internal ones. In contrast, hourglass clocks can remain accurate when internal irregularities are high but can be disturbed by external ones. Biological clocks affect the health of the entire organism and faulty clocks are implicated in numerous diseases. The study of Pittayakanchit, Lu et al. showed that the optimal architecture of a biological clock depends on the balance of irregularities in the external and internal environment of an organism. A next step will be to understand whether an organism can change its clock architecture while the environment changes. A better understanding of how biological clocks are regulated may help us find ways to tune faulty clocks to account for both the external environment and the internal state of an organism.