Driver fatigue – an accident waiting to happen
Box 1 | Circadian rhythms at the molecular level
Research into circadian rhythms has begun to shed some light on the phenomenon. Much of the research has been done on Drosophila melanogaster, a species of fly often used in genetic studies. By deliberately mutating the genes of these flies and then screening for changes in the circadian rhythm, scientists were able to identify the genes for controlling circadian rhythm – at least eight genes are thought to play a role. These genes were then sequenced – that is, the specific DNA code for the gene was determined – and the proteins produced by the genes identified. Scientists then worked out what these proteins did and how the circadian ‘clock’ actually operated.
Negative feedback loop
According to a simplified model, two genes called period and timeless code for the manufacture of two proteins called PER and TIM respectively. When the concentration of PER and TIM reaches a threshold level they are transported into the cell nucleus where they bind to transcription factors (proteins that initiate the transcription of a gene), shutting down further production of the two proteins; this is called a negative feedback loop. The concentrations of PER and TIM in the cell then declines as the existing molecules degrade; once the lower threshold concentrations are reached, their manufacture commences again. This rise and fall in the concentration of PER and TIM occurs on a roughly 24-hour cycle and is thought to play a major role in governing the circadian rhythm in Drosophila.
Resetting the biological clock
Similar but much more complex processes have now been identified in mammals. In humans (and many other species) the biological clock appears to work on a cycle between 24 and 25 hours in length. Under normal circumstances the biological clock is regularly ‘reset’ by a range of environmental cues, or ‘zeitgebers’ (‘time-givers’), the most important of which is light; thus, jet-lag is not a permanent condition because the internal clock will eventually be reset to match the new real-world conditions.
Related sites
Biological clocks (Brain Briefings, Society for Neuroscience, USA)
Overview of circadian rhythms (National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA)
Clockwork genes – discoveries in biological time (Howard Hughes Medical Institute, USA)
Circadian rhythms and clocks (All Science Den.com, USA)
Circadian rhythms (Kimball's Biology Pages, USA)
Posted December 2002.