![]() Most clock genes have a Per-Arnt-Sim (PAS) domain that mediates protein-protein interaction, regulates circadian rhythms and is related to transcription factors that act as heterodimers. The actual control of circadian rhythms is a complex process involving many environmental, genetic and physiological factors as reviewed by Wehr (1996). Virtually all body processes systematically fluctuate during the 24-hour period and shift daily in response to the changes in the length of the period of light and darkness. By serving as transcriptional activators, clock genes regulate their own expression by building up over a 24-hour period until they turn their genes off and start their cycles again. light) that affect the phase of the clock to regulate the daily patterning of physiology and behavior. Clock genes must cycle and respond rapidly to environmental signals (e.g. Exposure to light stimulates a cascade of molecular events in the circadian clock involving clock gene expression, which facilitates the daily synchronization to changes in photoperiod. One of the most pervasive epigenetic influences in the evolutionary process from single cell organisms to man is the 24-hour light/dark cycle. ![]() Now that they better understand the cellular clock, scientists can begin to manipulate it, with applications from curing jet lag to brightening winter depression.” ![]() Perhaps more amazing, fruit flies and mice–separated by nearly 700 million years of evolution–share the very same timekeeping proteins. Across the tree of life, from bacteria to humans, clocks use oscillating levels of proteins in feedback loops to keep time. In 1998, a volley of rapid-fire discoveries revealed the stunning universality of the clock workings. Modern biologists might in part agree, for it's clear that evolution has carefully crafted clocks that allow almost all organisms to follow the rhythm of the sun. The following is a quote from Science (December, 1998): “Nineteenth-century philosophers proposed that God was a clockmaker who created the world and let it run. For two years in a row (1997,1998), clock genes made the Runners Up list. (1) A subgroup of depressed patients have documented circadian abnormalities in mood, sleep, temperature and neuroendocrine secretion (2) It is also suggested that seasonal affective disorder (SAD) patients may show an abnormality in their ability to shift their daily circadian rhythms in response to seasonal light changes (3) The dramatic improvements in some depressions in response to three treatment modalities which manipulate circadian rhythms suggest that circadian abnormalities reported in patients may constitute a core component of the pathophysiology in depression (4) Mutations in clock genes have been discovered that accelerate or delay circadian cycles (5) It is hypothesized that 24-hour rhythm abnormalities in major depression and SAD may be due to altered clock genes.Įach year the journal Science evaluates all fields of science and lists the ten most important breakthroughs of the year. ![]() This paper reviews the recent discovery of clock genes that provide the mechanism for the regulation of circadian and seasonal rhythms in lower organisms and in humans and relates these clock genes to the circadian abnormalities in depression.
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