Molecular Mechanisms

Synchronization of physiological function and behavior to the solar day is ubiquitous among eukaryotic organisms and has been documented in a multitude of animal species. When animals such as molluscs, arthropods, birds, mammals, or humans are brought into the lab and exposed to constant conditions, many of the rhythms that they express in light:dark (LD) cycles persist and are thus termed "free-running" circadian rhythms. The presence of these persistent rhythms demonstrates control by (an) endogenous clock(s). Since they have been found in virtually all organisms in which a concerted effort has been made to find them (with the exception of the Archaebacteria), these clocks are considered ubiquitous and provide significant adaptive value.

Over the past two decades much has been learned about the molecular machinery of circadian clocks in species ranging from slime molds to mammals. In animals several common “core” clock proteins have been identified in organisms ranging from insects to mammals. These proteins are essential parts of two negative feedback loops that control their own expression (and of other genes) over 24 h periods. In brief, proteins such as PERIOD (PER), CLOCK (CLK), and TIMELESS (TIM) are generally expressed rhythmically and, as they accumulate, negatively feedback on their own expression. Although there are interesting species differences in the regulation of this clock (for example - TIM oscillates in Drosophila but not in the mouse), these proteins in particular appear to be a consistent molecular core of the circadian clock.