CIRCADIAN-RHYTHMS - FROM BEHAVIOR TO MOLECULES

In higher eukaryotes, circadian behaviour patterns have been dissected at the molecular level in Drosophila and, more recently, in the mouse . Considerable progress has been made in identifying some of the molec ular components of the clock in the fly, where two genes, period (per) and timeless (tim), are essential for behavioural rhythmicity. The PE R and TIM proteins show circadian cycles in abundance, and are part of a negative feedback loop with their own mRNAs. Within the pacemaker n eurons, the PER and TIM products are believed to form a complex which allows them to translocate to the nucleus, but how they repress their own transcription is unclear. TIM is rapidly degraded by light, a feat ure which permits a compelling molecular description of both behaviour al light entrainment and phase responses to light pulses. The regulati on of per and tim is altered in different Drosophila tissues, however, and comparative analyses of the two genes outside the Diptera reveals further unusual patterns of tissue-specific regulation. Evolution app ears to have modified the way in which the two genes are utilised to g enerate circadian phenotypes. More recently, the cloning of mouse cloc k genes, including putative per homologues, opens up exciting possibil ities for mammalian molecular chronobiology.