The search for circadian clock and sleep genes.

In recent years, there has been extraordinary progress in elucidating the molecular components of the mammalian circadian clock system. The discovery of circadian clock genes in lower organisms (such as fruit flies and fungi), which show many similarities with clock genes in mammals, together with advances in mouse molecular genetics have led to major new discoveries on the molecular and genetic basis of mammalian circadian rhythms. This article reviews both of these lines of research from an historical perspective and discusses how these lines have merged to provide unique insights into the molecular mechanisms of circadian function. The review also speculates on how the discovery of circadian clock genes may lead directly or indirectly to the discovery of mammalian sleep genes. The determination of the molecular mechanisms via which circadian clock genes (and their protein products) regulate the timing and the need for sleep, and the identification of new genes involved in sleep regulation, may produce new information on the genetic and molecular control of sleep which could ultimately lead to the development of new treatments for sleep disorders.