"There is an obvious biological basis to a 12-hour rhythm," Hogenesch says. "The 12-hour genes predicted dusk and dawn. These are two really, really stressful transitions that your body goes through and your mind goes through. Anybody who has young children realizes that they are more likely to cry around those times and you're more likely to cry with them." The shift in gene expression controlled by these harmonics can help an animal prepare for the behavioral and physiological changes that accompany the shift from light to dark and back.
"We have less of a handle on the 8-hour rhythms," he says, "but the fact that we can see them reliably means to me there is the possibility that there could be a biological basis to an 8-hour cycle."
Parallel experiments using RNA samples from synchronized tissue culture cells uncovered only genes that cycled on a 24-hour rhythm and showed no evidence of the shorter oscillations, suggesting that some of the timing cues are systemically controlled and some are controlled by the cell itself.
Feeding appears to control one of the 12-hour gene expression peaks. Mice consume about 20% of their daily calories right after they wake at dusk, which is near one gene expression peak. When the researchers restricted feeding to a different time of day one 12-hour peak disappeared and the other became more pronounced. "We were left with the autonomously driven circadian protein transcription the 24-hour component which was unshifted by the feeding change," Hogenesch says.
The high-density time sampling had an additional payoff: The team gained a sharper picture of the genes controlled by the 24-hour circadian clock. "We were able to more precisely measure the number of protein transcripts and the identity of the transcripts than we were able to with less frequent time sampling.
|Contact: Karen Kreeger|
University of Pennsylvania School of Medicine