The human body clock is complex. But if we could learn to control it—that is, advance and delay it—it could make a positive difference on people with jet lag and erratic work schedules. A team of researchers from the University of California, San Francisco thinks we are getting closer to understanding the body’s clock. Their work focuses on a mutant "clock" gene that makes some people "early to bed, early to rise," a condition known as familial advanced sleep phase syndrome (FASPS).

In the January 12, 2007, issue of the journal Cell, the UCSF researchers report new evidence that helps explain just how some individuals’ natural alarm clocks get set to such an early wake-up time. In studies of mice carrying the human FASPS gene, the researchers found that the mutant version of the Period 2 (Per2) clock gene—which is crucial for resetting the body’s central clock in response to light—cannot be chemically modified by another enzyme that controls it. That failure leads to a reduction in the number of copies of the Per2 "message," and the characteristic shifted sleep pattern.

"This study highlights the power of natural human mutations to uncover things (about the circadian clock) that we might not otherwise have learned, or that we might have misunderstood before," said Howard Hughes Investigator Louis Ptacek of UCSF.

FASPS is an inherited condition in which people are "early birds." They rise early and go to bed early. Those with the condition generally show changes in core body temperatures and other characteristics governed by the circadian clock that are shifted up by 3 to 4 hours. It takes just one copy of the abnormal gene to exhibit symptoms.

The researchers found that when the human gene was inserted into otherwise normal mice, it caused them to rise early—a symptom that mirrors the sign of FASPS in people.

The findings led the researchers to suggest a model of clock function in which cells sense changing Per2 levels over time, beginning a new daily cycle when a certain threshold is crossed. According to the researchers, the advance in understanding of Per2’s role may ultimately lead to methods for people to synchronize their internal clocks with their regular or changing routines.