Molecular genetics, circadian rhythms and sleep

Abstract

Sleep is a vital function present in all mammals and birds, but its phylogenetic origin remains uncertain. In humans, sleep represents over half the first year of life, and roughly a third of adult life. The total suppression of sleep will provoke death in animals [179]. The universal and irrevocable nature of this function, as well as the maintenance (conservation) of NREM sleep -REM sleep organisation in mammals and birds implies the existence of constitutional factors. However, a wide variability in phenotypes has been noted between species, animal strains and individuals of the same species, as well as in the duration of NREM sleep and REM sleep and their distribution throughout the nycthoemeral cycle. These variations may be attributed to environmental factors. Their role in sleep is well known whether in terms of physical effects (light, temperature) or behavioural effects (conditioning, diet). But these factors do not fully account for the variability observed and the physiological differences in “sleep” phenotypes both in animals and humans, suggesting that polymorphic genetic factors are involved in this function. Even for a relatively simple and anatomically localised function such as circadian rhythmicity in the suprachiasmatic nucleus, multiple genes appear to be involved. The situation is probably even more complex for the normal and abnormal regulation of sleep in general. Several sleep disorders (narcolepsy, certain forms of insomnia, sleep apnoea syndrome, restless legs syndrome and periodic limb movement disorder) are known to occur with high frequency in certain families, with a higher rate of concordance in monozygotic than in dizygotic twins, thus suggesting the presence of predisposing genetic factors. The mutations or polymorphisms of certain genes result in pathological phenotypes in animals and humans, whereas others contribute to interindividual differences for the various aspects of sleep.