Human clock genes.

Rhythmic variations in physiological and behavioural processes are mediated by both endogenous and exogenous factors. Endogenous factors include self-sustaining biological pacemakers or clocks which in the absence of strong external influences self-sustain periodic rhythms in such diverse physiological and psychological processes as core body temperature, food intake, cognitive performance and mood. Clocks with endogenous periods near or at 24 h (called circadian clocks from the Latin, circa dies, meaning about one day) have been documented from prokaryotes to single cell eukaryotes to multi-cellular, complex animals such as flies, rodents and humans. Over the past few years, a revolution in the understanding of the molecular basis of these clocks has led to the identification of a number of core clock genes and their proteins, and the development of elegant feedback models to explain the molecular gears of circadian clocks. At least eight human orthologs of mouse core clock genes have been identified, and polymorphisms in two of these, hClock and hPer2, have been implicated in human sleep disorders. Remarkably, knowledge of these core clock genes and the development of sophisticated reporter systems to monitor clock gene promoter activity have led to the astonishing observation that our body is actually composed of millions of cellular clocks and oscillators whose co-ordinated activity gives rise to pronounced daily, monthly, and seasonal rhythms in physiology and behaviour. An idea that is gaining favour is that our physical and mental well-being is probably determined by the appropriate phasing of these millions of cellular clocks with recurring, meaningful events in the environment.