Circadian clocks limited by noise

• Published in: Nature (London) 2000-01, Vol.403 (6767), p.267-268
• Main Authors: BARKAI, N, LEIBLER, S
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biological Clocks - physiology; Cell Physiological Phenomena; Chronobiology; circadian clocks; Circadian Rhythm - physiology; Drosophila; Fundamental and applied biological sciences. Psychology; Models, Biological; Monte Carlo Method; Neurospora; Protein Biosynthesis; RNA, Messenger - metabolism; Stochastic Processes; Synechococcus; Transcription, Genetic; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35002258

Circadian rhythms, which provide internal daily periodicity, are used by a wide range of organisms to anticipate daily changes in the environment. It seems that these organisms generate circadian periodicity by similar biochemical network within a single cell. A model based on the common features of these biochemical networks shows that a circadian network can oscillate reliably in the presence of stochastic biochemical noise and when cellular conditions are altered. We propose that the ability to resist such perturbations imposes strict constraints on the oscillation mechanisms underlying circadian periodicity in vivo. There is evidence that clock networks share common features in a wide range of organisms, from cyanobacteria to mammals. For instance, all networks seem to include an interaction between two types of component: positive elements (or activators, such as KaiA in Synechococcus, Wc1-2 in Neurospora, Clc and Cyc in Drosophila, and Clock and Bmal in mice) enhance the expression of negative elements (or repressors, such as KaiB and KaiC in Synechococcus, Frq in Neurospora, Tim and Per in Drosophila, and Tim and Per1,2 and 3 in mice). The evidence indicates that the clock network is based predominantly on transcriptional regulation. Although the contribution of post-transcriptional regulation to the oscillation mechanism is not yet clear, and it is too early to be sure that all the components and their interactions have been revealed in any single organism, we can already address the question of whether the common features of circadian networks are consequences of some underlying "design principles". We can envisage many types of biochemical network that produce periodic oscillations and that can be entrained to a 24-hour period by an external periodic stimulus, such as light or temperature. But there are additional constraints: for example, the period of all autonomous circadian clocks must remain relatively constant over a wide temperature range, a property known as temperature compensation.