Retiring from a naval engagement in 1588, the captains of the Spanish Armada lost their way rounding the coast of England. They had hoped to sail west, far out to sea before turning south toward home, thereby dodging the rocky coastline and hostile company. But lacking an accurate timepiece to take longitude readings, they could only guess their westward progress and turned south too soon.
The fleet was decimated on the shoals of Ireland.
The captains of the foundering ships would never learn of the clock provided by nature to any creature who would heed its ticking, or the insect with a brain no larger than the head of a pin that uses a tiny biological timepiece to navigate each year across an entire continent.
A Living Clock
The circadian clock can be observed operating in many species of plants and animals, tapping out its rhythm in 24-hour cycles, said Steven Reppert, professor of neurobiology at the University of Massachusetts Medical School.
“The clustering of sleep during the nighttime hours is largely due to the circadian system,” he explained. However, he added that “it is also felt this system controls other aspects of bodily function, including a number of metabolic processes, in ways which are just now beginning to be uncovered.” And researchers at the Oregon Health & Science University recently reported that psychiatric disorders, such as major depressive episodes, also appear to be under the influence of the circadian clock.
Reppert leads the medical school’s research program investigating the molecular mechanism of circadian clocks in animals. He said a great deal of progress has been made by studying the clock mechanism in the fruit fly and the mouse. From these studies, he said, “We knew the genes and the protein products that were associated with the clock,” and researchers have now “built feedback loops showing how a timing mechanism would work biologically.”
But “one issue remains unresolved: How does this core clock mechanism connect to behavior?”
Reflecting on his lifelong fascination with butterflies, Reppert said that six years ago, he decided to turn to the monarchs for an answer.
“Here we had this animal that underwent this spectacular migration over long distances. The butterflies doing this were at least two or three generations removed from those who had been there before, so we thought we were dealing with a genetic program that was turned on in the butterfly at a particular time of year, compelling those animals to make this long journey.”
Reppert said his research focused on understanding how the brain works. His work discovered a very interesting way “in which a circadian clock interacts with another area of the brain and incorporates this information about time and space.
“If we can understand that process, the fundamental mechanisms behind that may ultimately be applicable to the mammalian brain and even to the human brain in terms of different processes.”
Plus, Reppert said, the circadian clock in the butterflies plays a key role in helping them navigate as a central component of their time-compensated sun compass.
According to Reppert, this compass integrates two pieces of information in the butterfly brain: environmental cues from skylight and time cues from the insect’s circadian clock.
“For butterflies and other animals that migrate over long distances during the day, the most consistent landmark is some aspect of the skylight — whether it’s the sunlight, polarized light or spectral intensity gradients throughout the sky. But all of those would move in a relatively constant pattern, as the sun itself appears to move across the sky. So, if that’s what an animal uses to maintain a fixed bearing, they have to correct for that movement.
“It’s a dynamic process that’s continually being modulated in the butterflies’ brain.
“We’ve known a lot over the years about how light information is integrated by the sun compass, but how the animals compensate for the movement of the sun — which is the circadian clock’s responsibility — had not really been studied.”
One-Celled Clock
The functional components of the circadian clock mechanism are genes, proteins and molecules of ribonucleic acid, or RNA. But, Reppert said, “The important thing about this clock is that it is contained within a single cell” and that “these cells can be found in the brain or in the liver or other tissues.”
In fact, according to Reppert, there are clocks all over the body, and “at the molecular level, their mechanisms are virtually identical.”
Reppert explained that certain proteins within the cell turn on the activities of genes, prompting them to produce RNA molecules. These molecules, in turn, are translated into a different set of proteins that “feed back and talk to the transcription factors and shut down the transcription of the loop.” Then the process starts all over again.
“This feedback loop continues day in and day out,” Reppert said. “If you take this area of the brain out and you dissect out the single cells in culture, what you find is that they still maintain their intrinsic property to give rhythms in — let’s say — the firing rate of the neurons. You can watch this clock tick at a molecular level for years in single cells. It’s quite remarkable.”
In mammals, the main clock is located in the brain, housed in a small structure of the hypothalamus called the suprachiasmatic nucleus. “That area of the brain is sort of the orchestra leader of all the other clocks in the body. It senses light information and keeps all the other clocks coordinated with what’s going on in the outside world,” Reppert said.
The human version of this structure comprises about 20,000 neurons.
In the butterfly brain, by contrast, the primary timekeeper cells number exactly four — two on either side of the area thought to be responsible for motor activity.
Despite this vast difference in scale, Reppert found a surprising affinity between the butterfly clock and our own.
Not So Different
“What we discovered in the butterfly brain was a clock mechanism that was not felt to exist in insects.” It was, he said, “more like the human clock than it is like the fruit fly clock.
“The effects of the timing system on us humans is pretty amazing and is much more widespread than we thought before we had the benefit of the molecular biology studies of the past decade.
“That’s where core biology is today,” Reppert said. “The underlying biological principles are universal. Studying organisms like the butterfly or other insects shows that over the course of evolution, certain processes have been conserved because they’ve turned out to be very useful under selective pressures. A lot of what’s going on in the butterfly at a molecular level is very similar to what’s going on in us.
“I think the more we learn about the butterfly, the more we’re going to learn about ourselves. Understanding their biology, I think, will have implications for understanding human biology.”
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