ABSTRACT

Circadian rhythms regulate daily fluctuations in cellular processes, physiology, and behavior that occur in nearly all organisms, from mammals to bacteria. The transcription-translation negative feedback models of the circadian oscillator, based on the period (per) and timeless (tim) genes in Drosophila and the frequency (frq) gene in Neurospora, are attractive and provide a working hypothesis for the generation of circadian rhythmicity in cells. The circadian gene Clock was the first to be cloned using forward genetics in mammals. Obviously, not all mammalian circadian rhythm genes must be identified using forward genetics alone. Due to the interactive nature of the negative feedback loop model, molecular biology remains an important tool for the isolation of circadian genes. The combination of genetic and molecular techniques has brought the mammalian circadian field to a period of discovery similar to that experienced in Drosophila.