NASHVILLE, Tenn. – A traveler experiences jet lag when his or her
internal clock becomes out of synch with the environment. Seasonal
Affective Disorder, some types of depression, sleep disorders and
problems adjusting to changes in work cycles all can occur when an
individual’s biological clocks act up. Recent studies have even found
links between these molecular time pieces and cancer.
Microscopic pacemakers–also known as circadian clocks–are found in
everything from pond scum to human beings and appear to help organize a
dizzying array of biochemical processes. Despite the important role
that they play, scientists are just beginning to understand the
benefits that these internal pacemakers provide when they work and the
problems they cause when they malfunction.
A study performed by researchers at Vanderbilt University and published
in the Aug. 24 issue of the journal Current Biology sheds new light on
this issue. Using blue-green algae-the simplest organism known to
possess these mechanisms-the researchers report that the benefits of
biological clocks are directly linked to environments with regular
day/night cycles and totally disappear in conditions of constant
illumination.
"Circadian clocks are so widespread that we think they must enhance the
fitness of organisms by improving their ability to adapt to
environmental influences, specifically daily changes in light,
temperature and humidity," says Carl H. Johnson, professor of
biological sciences and a Kennedy Center investigator who directed the
study. "Some people have even suggested that, once invented, these
clocks are such a powerful organizational tool that their benefits go
beyond responding to external cycles. However, there have been
practically no rigorous tests of either proposition."
To test these ideas directly, Johnson’s research team used genetic
engineering techniques to completely disrupt the biological clocks in
one group of algae and to damp the frequency of the clocks in a second
group. The researchers were careful to employ "point" mutations in the
clock genes that didn’t stunt the growth of the microscopic plants.
They then mixed the algae that had disrupted clocks with algae having
normally functioning clocks. When the mixture was placed in an
environment with a 24-hour day/night cycle, the normal algae grew
dramatically faster than those that lacked functional internal timers.
The normal algae also outperformed the algae with the damped clocks,
but by a smaller margin.
The result was presaged by a series of experiments that Johnson
conducted in 1998 with Susan S. Golden from Texas A&M University
and Takao Kondo from Nagoya University. In the previous experiments,
the researchers created two new algae strains with clocks of 22 hours
and 30 hours. (The frequency of the biological clocks in normal
blue-green algae is 25 hours.) They created mixed colonies by combining
the strains in pairs: wild type and 22 hour; wild type and 30 hour; 22
hour and 30 hour. Then they put these mixed cultures into incubators
with three different light-dark cycles-22 hours, 24 hours and 30
hours-and monitored them for about a month.
When they pulled the cultures out, the researchers found that the
strain whose internal clock most closely matched the light-dark cycle
invariably outgrew the competing strain. In fact, they found that the
selective advantage of having the correctly tuned biological clock was
surprisingly strong: The strains with matching frequencies grew 20 to
30 percent faster than the out of synch strains.
The second part of the current experiment was designed to test whether
the biological clocks also provide an intrinsic advantage, a hypothesis
advanced by the late Colin Pittendrigh of Stanford. He suggested that
circadian clocks might be beneficial even in an unchanging environment.
There was some indirect support for this proposition. In one
experiment, for example, populations of the fruit fly, Drosophila
melanogaster, were raised in constant illumination for hundreds of
generations. Nevertheless, their biological clocks continued to
function, suggesting that they continue to have adaptive value.
When the algae strains were placed in a chamber with constant light,
however, the researchers were surprised to discover that the shoe was
on the other foot: The algae with the disrupted internal clock divided
and grew at a slightly faster rate than their clockwatching cousins,
both those with natural biological clocks and those whose clocks were
damped.
"This was the most surprising result of our study," says Johnson.
"Under constant conditions, the circadian clock system is of no benefit
and, in fact, might even be bad for the algae."
The scientist doesn’t know for certain why this happens, but he has
some ideas. The microscopic plants use their biological clocks to turn
their photosynthesis system on and off. In a normal 14-hour day/night
cycle, this allows the microscopic plant to maximize the amount of
chemical energy it can extract during daylight.
"In constant illumination, however, the biological clocks may keep
shutting down photosynthesis in expectation of the darkness that never
comes," says Johnson.
Co-authors on the study are post-doctoral fellows Mark A. Woelfle and
Yan Ouyang and graduate student Kittiporn Phanvijhitsiri. The research
was supported by the National Institutes of Health.
For more news about Vanderbilt research, visit Exploration,
Vanderbilt’s online research magazine at www.exploration.vanderbilt.edu.
Media contact: David F. Salisbury, (615) 343-6803
david.salisbury@vanderbilt.edu