Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Insight into how the body tells time

25.06.2002


You may feel different at the dreary hour of 4 a.m. than you do mid-afternoon at 4 p.m. Now, researchers might understand why. A study from Washington University School of Medicine in St. Louis helps explain how genes dictate our biological clock.



Nearly all living things have a natural rhythm that influences their behavior and physiology. This rhythm typically is "circadian", following a near 24-hour cycle. Driven by an internal clock, a creature’s natural rhythm is synchronized to the outside world by external cues, like the sun. So far, the products of eight different genes have been discovered to be essential to the operations of this clock. Scientists believe that these genes, in turn, somehow influence the expression of other genes throughout the body in order to control the timing of behaviors like sleep and wakefulness.

Researchers from three laboratories at the School of Medicine, in collaboration with a team at Affymetrix, have identified 22 genes that appear to be rhythmically regulated by the internal clock of the Drosophila fly and found hundreds more genes that are regulated by both light and the internal clock. The study appears in the June 24 issue of the Proceedings of the National Academy of Sciences.


"Understanding how our internal environment responds to our innate biological clock could help us develop better ways of adjusting to challenging circumstances, like unusual work shifts or jet lag following a long journey," says lead investigator Paul H. Taghert, Ph.D., professor of anatomy and neurobiology.

The fruit fly Drosophila melanogaster is one of the most commonly studied organisms, particularly in the pursuit of understanding biological clocks. In the past, researchers only could estimate the number of genes affected by the eight clock genes. But now that the fly’s genome has been fully sequenced, scientists can scrutinize nearly all of the animal’s 14,000 genes.

The Washington University team capitalized on the genome database now available. Using a relatively new technology called DNA microarrays – comprehensive lists of all the active genes in a tissue sample – they measured the expression levels of nearly 14,000 genes at various time-points in the heads of normal flies and in flies missing one of the clock genes, called period.

All flies were exposed to light for 12 hours, followed by dark for 12 hours. The cycle continued for a total of 96 hours. Genetic analyses were performed on half of the flies at six different time-points on the fifth day.

The remaining flies were transferred into complete darkness for 48 hours. On the third day of darkness, the team again analyzed gene expression at each of six time-points. By exposing flies to constant darkness, the team hoped to detect genetic changes that are regulated by the internal circadian timekeeping system, rather than by external cues.

Overall, the researchers obtained over 70 readings for each of the nearly 14,000 genes, generating about a million individual measurements.

Using sophisticated computer-based statistical analyses, the team determined that between 72 and 200 of the flies’ 14,000 genes showed significant rhythms of gene expression in normal flies living in a daily light-dark cycle. Of these 72 genes, 22 continued to fluctuate when flies were collected after three days of complete darkness. This implies that these 22 genes are driven by the internal, circadian clock, not by external cues such as light.

Mutant flies lacking the period gene also were placed into the same two experimental conditions – light and dark fluctuations compared with complete darkness. The flies exposed to alternating light and dark still showed 18 genes with persistent, rhythmic oscillations, demonstrating that light and dark can directly drive rhythmic gene expression.

The remaining 32 of the 72 oscillating genes only fluctuated rhythmically in animals that still had the period gene and who were exposed to light and dark conditions. The biologic functions of most of these oscillating genes are unknown.

One of the most surprising results of the study was the discovery of hundreds of genes whose levels did not fluctuate with time of day, but responded drastically to different lighting conditions or to the presence or absence of a circadian clock.

"The fly’s ability to regulate a large fraction of all its genes depending on a combination of day length and the circadian clock gives us an attractive model for understanding seasonal timekeeping," says co-author Russell N. Van Gelder, M.D., Ph.D., assistant professor of ophthalmology and visual sciences. "Defects in seasonal timekeeping are thought to be related to seasonal affective disorder (SAD), in which individuals experience recurrent depression during the short days of winter."

Three similar studies were published immediately preceding this paper, each estimating the number of genes controlled by the internal clock to be more than 100. Eighteen of the 22 genes identified in this study also were identified by one of the other three studies. However, the majority (84 percent) of the remaining genes identified by the other three groups were not included in any of the other lists.

"We feel that our analysis provides a minimal set of circadian genes about which we can feel fairly confident," says Taghert.

In an effort to optimize research initiatives, the School of Medicine team has posted all of their raw data on the Internet at http://circadian.wustl.edu.


Lin Y, Han M, Shimada B, Wang L, Gibler TM, Amarakone A, Awad TA, Stormo GD, Van Gelder RN, Taghert PH. Influence of the period-dependent circadian clock on diurnal, circadian, and aperiodic gene expression in Drosophila melanogaster. Proceedings of the National Academy of Sciences, June 24, 2002.

Funding from the National Institutes of Health, the Medical Scientist Training Program, the Research to Prevent Blindness Career Development Award, the Becker/AUPO/RPB Clinician-Scientist Award and from the Human Frontier Science Program Organization supported this research.


Gila Z. Reckess | EurekAlert!

More articles from Life Sciences:

nachricht Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>