Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
Biophys J. 1999 Nov;77(5):2411-7. doi: 10.1016/S0006-3495(99)77078-5. Epub 2008 Nov 21.
Many organisms display rhythms of physiology and behavior that are entrained to the 24-h cycle of light and darkness prevailing on Earth. Under constant conditions of illumination and temperature, these internal biological rhythms persist with a period close to 1 day ("circadian"), but it is usually not exactly 24h. Recent discoveries have uncovered stunning similarities among the molecular circuitries of circadian clocks in mice, fruit flies, and bread molds. A consensus picture is coming into focus around two proteins (called PER and TIM in fruit flies), which dimerize and then inhibit transcription of their own genes. Although this picture seems to confirm a venerable model of circadian rhythms based on time-delayed negative feedback, we suggest that just as crucial to the circadian oscillator is a positive feedback loop based on stabilization of PER upon dimerization. These ideas can be expressed in simple mathematical form (phase plane portraits), and the model accounts naturally for several hallmarks of circadian rhythms, including temperature compensation and the per(L) mutant phenotype. In addition, the model suggests how an endogenous circadian oscillator could have evolved from a more primitive, light-activated switch.
许多生物体表现出生理和行为的节律，这些节律与地球上普遍存在的 24 小时光暗循环同步。在恒定的光照和温度条件下，这些内部生物节律以接近 1 天的周期（“昼夜节律”）持续，但通常不是恰好 24 小时。最近的发现揭示了小鼠、果蝇和面包霉菌昼夜节律钟的分子电路之间惊人的相似性。一个共识的画面正在围绕两种蛋白质（在果蝇中称为 PER 和 TIM）聚焦，这两种蛋白质二聚化，然后抑制自身基因的转录。尽管这个画面似乎证实了基于时间延迟负反馈的古老的昼夜节律模型，但我们认为，对于昼夜节律振荡器来说，同样至关重要的是基于 PER 二聚化稳定的正反馈环。这些想法可以用简单的数学形式（相平面图）来表示，该模型自然解释了昼夜节律的几个特征，包括温度补偿和 per(L) 突变表型。此外，该模型还表明，内源性昼夜节律振荡器如何从更原始的、光激活的开关进化而来。
