The search for circadian clock components in humans: new perspectives for association studies

Individual circadian clocks entrain differently to environmental cycles (zeitgebers, e.g., light and darkness), earlier or later within the day, leading to different chronotypes. In human populations, the distribution of chronotypes forms a bell-shaped curve, with the extreme early and late types _ larks and owls, respectively _ at its ends. Human chronotype, which can be assessed by the timing of an individual's sleep-wake cycle, is partly influenced by genetic factors - known from animal experimentation. Here, we review population genetic studies which have used a questionnaire probing individual daily timing preference for associations with polymorphisms in clock genes. We discuss their inherent limitations and suggest an alternative approach combining a short questionnaire (Munich ChronoType Questionnaire, MCTQ), which assesses chronotype in a quantitative manner, with a genome-wide analysis (GWA). The advantages of these methods in comparison to assessing time-of-day preferences and single nucleotide polymorphism genotyping are discussed. In the future, global studies of chronotype using the MCTQ and GWA may also contribute to understanding the influence of seasons, latitude (e.g., different photoperiods), and climate on allele frequencies and chronotype distribution in different populations.

Several clocks may simplify the circadian system of Gonyaulax

The circadian system of Gonyaulax involves at least two pacemaking oscillators. These oscillators have been shown to be distinct at the physiological level by an examination of their rhythmic periods under different conditions, their phase response to pulses of light and darkness and their ability to compensate the rhythms for changes in temperature. It is also known that Gonyaulax can restrict synthesis of different proteins to at least three different times of day. We suggest that the two known oscillators may each control synthesis of a differently timed class of proteins.