A biological basis for the 8-hou...( PHILADELPHIA - The circadian clock c...)

PHILADELPHIA - The circadian clock coordinates physiological and behavioral processes on a 24-hour rhythm, allowing animals to anticipate changes in their environment and prepare accordingly. Scientists already know that some genes are controlled by the clock and are turned on only one time during each 24-hour cycle. Now, researchers at the University of Pennsylvania School of Medicine and the Salk Institute for Biological Studies found that some genes are switched on once every 12 or 8 hours, indicating that shorter cycles of the circadian rhythm are also biologically encoded. Using a novel time-sampling approach in which the investigators looked at gene activity in the mouse liver every hour for 48 hours, they also found 10-fold more genes controlled by the 24-hour clock than previously reported.

This the first report where researchers have found other periodicities than the 24-hour cycle functioning in a live animal.

These findings, which appear in the April issue of PLoS Genetics, have implications for better understanding disruptions to normal circadian rhythms that contribute to a host of pathologies such as cardiovascular and metabolic disease, cancer, and aging-related disorders.

"The principal frequency, which is not a surprise, is the 24-hour cycle, and it is the most prevalent," says senior author John Hogenesch, PhD, Associate Professor of Pharmacology in the Institute for Translational Medicine and Therapeutics at Penn. "What was a surprise to us although we set up the experiment to see exactly this are the 12-hour and the 8-hour cycles.

To uncover these shorter oscillations, the Hogenesch and Salk team isolated RNA from the livers of mice every hour for 48 hours. Microarray analysis showed that more than 3,000 genes were expressed on a circadian rhythm which account for approximately 4% of all of the genes expressed in the liver. Additionally, 260 genes were expressed on a 12-hour cycle and 63 genes
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