The mechanism, presumed to exist within many animals and plants, that produces regular periodic changes in behaviour or physiology. Biological clocks underlie many of the biorhythms seen in organisms (e.g. sleep-wake cycle, hibernation in animals). They continue to run even when conditions are kept artificially constant, but eventually drift out of step with the natural environment without the specific signals that normally keep them synchronized. Studies in the fruit fly Drosophila have revealed the molecular basis of the biological clock, and similar mechanisms are thought to occur in other animals, including mammals, and in plants, fungi, and cyanobacteria. It involves various proteins encoded by ‘clock genes’, some of which serve as transcription factors for their own genes; examples of clock genes in Drosophila and other animals are PER (encoded by the per gene) and TIM (encoded by the tim gene). These form part of a negative feedback loop in which the concentration of the proteins cyclically rises and falls. The timing of each cycle is determined by the time required for transcription, export of messenger RNA to the cytoplasm, translation, and, crucially, the formation of PER-TIM dimers—the only form in which these two proteins can enter the nucleus. Also, some of the proteins, including TIM, are sensitive to light and are degraded during the day. Hence, the biological clock is entrained to the day-night cycle. Although the clock proteins differ in different organisms, similar mechanisms have evolved independently in diverse organisms. In humans the central oscillator of the biological clock resides in the paired suprachiasmatic nuclei (SCN), lying above the optic chiasma deep within the brain. They receive input from the retina of the eyes to synchronize the ‘clock’ with the day-night cycle. Genes of the human ‘clock’ are also expressed cyclically in other tissues, such as the liver, heart, and skin, acting as peripheral clocks. These are synchronized with the central SCN oscillator but may also be entrained by other factors, such as mealtimes. Human equivalents of the Drosophila proteins are PER and CRY, which interact with a complex of two other proteins, CLOCK and BMAL1, to regulate expression of their own genes over a roughly 24-hour cycle. In 2017 the US scientists Jeffrey Hall, Michael Rosbash, and Michael Young won the Nobel Prize for physiology or medicine for their work on biological clocks.

http://millar.bio.ed.ac.uk/ Introduction to circadian rhythms and other aspects of chronobiology, hosted by the Millar Lab at Edinburgh University