As jet-lag sufferers know, the body's 24-hour clock delivers a powerful timekeeping signal. In recent years, clock researchers have uncovered some of the gears and springs that keep this circadian timepiece running, largely by identifying a handful of key genes in organisms from bread mold to mice. In today's issue of Cell, a team reports that it has found in mice and humans a close relative of a fruit fly clock gene--the first evidence that some of these genes may have been conserved over the course of evolution.
Molecular geneticist Cheng Chi Lee, developmental biologist Gregor Eichele, and their co-workers at the Baylor College of Medicine in Houston have isolated a gene in mice and humans that shares 44% of the amino acid sequence of the period (per) gene of the fruit fly Drosophila melanogaster. Like the per gene, the new genes--dubbed RIGUI in humans and m-rigui in mice--are turned on and off in a daily cycle and may work with other genes to generate the oscillating mechanism that runs the internal clock.
"This is an extremely interesting piece of work," says Joseph Takahashi of Northwestern University in Evanston, Illinois. "This is really the first molecular link between the Drosophila clock gene story and the emerging mouse gene story." Other clock researchers caution that it is too soon to be sure that RIGUI serves the same function in mice and humans that per does in fruit flies. Steven Reppert of Massachusetts General Hospital in Boston says that the only way to prove this would be to knock out the mouse gene and see what happens to the circadian rhythms.
Lee and his colleagues are now embarking on just such experiments, and other clock researchers will not be far behind. Despite their reservations, Reppert and other researchers agree that the new results are likely to open new doors in clock research. "We will now be able to test molecular models of the clock in mammals," says Takahashi. "Once we get a couple of these genes, the next ones will start falling into place."