A look inside a wristwatch reveals that timekeeping is a complex affair, involving the coordination of mechanical parts providing the impulses and feedback needed to achieve precisely recurring movement. Biological clocks are equally complex, regulated by a network of genes and transcriptional factors that interact to stabilize the rhythms of numerous physiological systems. Unlike the wristwatch, however, there is no visible readout or display showing an individuals body time, a lack which has stood as one of the major barriers to realizing the promise of chronotherapy, which seeks to deliver drug treatments at optimal body times.
A new study by Hiroki R. Ueda (Laboratory for Systems Biology, RIKEN Center for Developmental Biology; Kobe, Japan) and colleagues has provided proof of principle that just such a display of individual body time may one day possible. The report, published in the August 3 issue of the Proceedings of the National Academy of Sciences, describes the analysis of the expression of more than 100 time-indicating genes in the mouse. The results of this genome-wide study enabled the authors to develop a "molecular timetable" that provides an accurate representation of the animals body time based on the sampling of gene expression levels at a single point in time.
Many genes exhibit variable expression cycles roughly over the course of a 24-hour day, a phenomenon known as circadian rhythmicity. In their study, Ueda et al. first identified genes that are expressed in high amplitude circadian patterns. Such genes demonstrate cyclical expression irrespective of variations in exposure to light, maintaining their amplitude and periodicity even when the animals are kept in constant darkness. The team identified 168 genes fulfilling these criteria in samples from mouse liver, and calculated their peak expression times in terms of both external time and the animals subjective inner clock. They found that the genes could be organized into a kind of daily schedule by their times of peak expression – some were expressed most highly at daybreak, some at dusk, some at other time-points throughout the cycle of a single day.
Doug Sipp | EurekAlert!
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