Molecular chronobiology

Recent years have seen exciting advances in the understanding of the mechanisms that underlie circadian rhythms in a variety of organisms, including mammals. Several key genes have been identified, whose products can be considered to represent bone fide clock molecules. Furthermore it appears that the same genes are important in generating rhythmic behaviour in both insects and man. There are some differences in the way these genes generate circadian output in the different taxa, but overall, the level of conservation of sequence and function is striking. The basic molecular oscillatory mechanism depends on a transcriptional/translational negative feedback loop, in which the PERIOD proteins play a cardinal role, together with other molecules, which interact to regulate circadian gene expression. In mammals, the brain oscillator resides in the suprachiasmatic nucleus, and its location in the hypothalamic region may have implications for understanding the rhythmic nature of some headache syndromes.