Circadian time keeping: the daily ups and downs of genes, cells, and organisms

Abstract

Light-sensitive organisms - from cyanobacteria to humans - contain circadian clocks that produce approximately 24-h cycles in the absence of external time cues. In various systems, clock genes have been identified and their functions examined. Negative feedback loops in clock gene expression were initially believed to control circadian rhythms in all organisms. However, recent experiments with cyanobacteria and the filamentous fungus Neurospora crassa tend to favour protein phosphorylation cycles as the basic timekeeper principle in these species. The study of clock genes in mammals has led to a further surprise; practically all body cells were found to harbour self-sustained circadian oscillators. These clocks are co-ordinated by a central pacemaker in the animal, but they keep ticking in a cell-autonomous fashion when maintained in tissue culture. In mammals, most physiology is influenced by the circadian timing, including rest-activity rhythms, heartbeat frequency, arterial blood pressure, renal plasma flow, urine production, intestinal peristaltic motility, and metabolism.