About Careers Internship MedBlog Contact us
Medindia LOGIN REGISTER
Advertisement

New Mammalian Clock Gene Identified by Bioinformatics Profiling

by Himabindu Venkatakrishnan on April 23, 2014 at 11:01 AM
 New Mammalian Clock Gene Identified by Bioinformatics Profiling

Researchers have characterized a set of clock genes over the last few decades that drive daily rhythms of physiology and behavior in all types of species, ranging from flies to humans. Over 15 mammalian clock proteins have been identified, but researchers surmise there are more. A team from the Perelman School of Medicine at the University of Pennsylvania wondered if big-data approaches could find them.

To accelerate clock-gene discovery, the investigators, led by John Hogenesch, PhD, professor of Pharmacology and first author Ron Anafi, MD, PhD, an instructor in the department of Medicine, used a computer-assisted approach to identify and rank candidate clock components. This approach found a new core clock gene, which the team named CHRONO. Their findings appear this week in PLOS Biology.

Advertisement

Hogenesch likens their approach to online profiling of movie suggestions for customers: "Think of Netflix. Based on your personalized movie profile, it predicts what movies you may want to watch in the future based on what you watched in the past." He thought the team could use this approach to identify new clock genes, given criteria already established from the "behavior" of known clock genes identified in the past two decades:

  • Clock genes cause oscillations at the messenger RNA and protein level.
  • Clock proteins physically interact with other clock proteins to form complexes that control daily rhythm inside cells.
  • Disruption of clock genes in cell models cause changes in observable behavioral and metabolic traits on a 24-hour cycle.
  • Clock genes are conserved across 600 million years of evolution from fruitflies to humans.

Advertisement

"We used a simple form of machine learning to integrate biologically relevant, genome-scale data and ranked genes based on their similarity to known clock proteins," explains Hogenesch. Using biological big data such as that found in the Circadian Expression Profile Data Base (CircaDB) to search for new clock genes, the Penn team evaluated the features of 20,000 human genes to isolate other genes that have the same clock-gene characteristics. "The hypothesis is that other genes that functionally resemble known clock genes are more likely to be clock genes themselves, just like movies that resemble your old favorites are more likely to become new favorites," says Anafi.

They found that several of the genes they identified physically interact with known clock proteins and modulate the daily rhythm of cells. One candidate, dubbed Gene Model 129, interacted with BMAL1, a well-known core clock component, and repressed the key driver of molecular rhythms, the BMAL1/CLOCK protein complex that guides the daily transcription of other proteins in a complicated system of genes that switch on and off over the course of the 24-hour day.

Given these results, the team renamed Gene Model 129, CHRONO, for computationally highlighted repressor of the network oscillator. The litmus test for identifying clock genes, however, is whether they regulate behavior: In mice in which CHRONO had been knocked out, Hogenesch found that the mice had a prolonged circadian period.

A companion study by colleagues at RIKEN in Japan and the University of Michigan, using a genome-wide analysis instead of a machine-learning approach, produced similar findings. Both studies link CHRONO to BMAL1. In the future, Anafi and Hogenesch will be investigating whether CHRONO regulates sleep, as most clock genes influence this behavior.

Source: Eurekalert
Font : A-A+

Advertisement

Advertisement
Advertisement

Recommended Readings

Latest Research News

Insight into Cellular Stress: Mechanisms Behind MRNA Sequestration Revealed
The discovery deepens our understanding of m6A biology and stress granule formation, with implications for neurodegenerative diseases.
Disrupted Circadian Rhythm Elevates the Risk of Parkinson's Disease
Trouble with sleep and the body's clock may increase your risk for Parkinson's, as per a new study.
A Wake-Up Call for Women — Hot Flashes Could Point to Alzheimer's Risk
New study uncovers a link between nocturnal hot flashes and Alzheimer's risk in menopausal women, suggesting a potential biomarker.
Breakthrough Brain-Centered Approach Reduces Chronic Back Pain
Our discovery revealed that a minority of individuals attributed their chronic pain to their brain's involvement.
New Statement to Protect Athletes' Health Published
Relative Energy Deficiency in Sport syndrome is overlooked by athletes and can be worsened by 'sports culture' due to its perceived short-term performance benefits.
View All
This site uses cookies to deliver our services.By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use  Ok, Got it. Close
MediBotMediBot
Greetings! How can I assist you?MediBot
×

New Mammalian Clock Gene Identified by Bioinformatics Profiling Personalised Printable Document (PDF)

Please complete this form and we'll send you a personalised information that is requested

You may use this for your own reference or forward it to your friends.

Please use the information prudently. If you are not a medical doctor please remember to consult your healthcare provider as this information is not a substitute for professional advice.

Name *

Email Address *

Country *

Areas of Interests