Nav: Home

Timing is everything, to our genes

February 08, 2018

LA JOLLA -- (Feb. 8, 2018) To everything there is a season. This saying applies to many human endeavors, but new research shows it's even true on the molecular level. A Salk Institute study published in the journal Science on February 8, 2018, found that the activity of nearly 80 percent of genes follows a day/night rhythm in many tissue types and brain regions.

While scientists have long known that many tissues follow these cycles, called circadian rhythms, this is the most comprehensive study connecting timing to gene transcription (the process of copying DNA into RNA to guide protein assembly).

"This is the first time a reference map of daily gene expression has been established," says Satchidananda Panda, a professor in Salk's Regulatory Biology Laboratory and senior author on the paper. "It's a framework to understand how circadian disruption causes diseases of the brain and body, such as depression, Crohn's disease, IBD, heart disease or cancer. This will have huge impact on understanding the mechanisms or optimizing cures for at least 150 diseases."

Using RNA sequencing, the research team tracked gene expression in dozens of different non-human primate tissues every 2 hours for 24 hours. The team found that each tissue contained genes that were expressed at different levels based on the time of day. However, the number of these "rhythmic" genes varied by tissue type, from around 200 in pineal, mesenteric lymph nodes, bone marrow and other tissues to more than 3,000 in prefrontal cortex, thyroid, gluteal muscle and others. In addition, genes that were expressed most often tended to show more rhythmicity, or variability by time.

Of the 25,000 genes in the primate genome, nearly 11,000 were expressed in all tissues. Of those (which mostly govern routine cellular functions, such as DNA repair and energy metabolism), 96.6 percent were particularly rhythmic in at least one tissue, varying drastically by when they were sampled.

In most of the tissues, gene transcription peaked in the early morning and late afternoon and quieted in the evening after dinner, around bedtime. With 81.7 percent of protein-coding genes experiencing a rhythmic effect, this timing mechanism is far more widespread than previously suspected.

"These findings provide new insights that could influence how scientific research is validated. For example, scientists trying to replicate previous work may pay closer attention to when specific assays were conducted," says the paper's co-senior author Howard Cooper, who is a visiting scientist at the Salk Institute. Aside from informing new research methods, this molecular timing mechanism could also impact drug effectiveness. In the future, pharmacists may provide patients more detailed instructions on how often and when to take drugs.

"We show that more than 80 percent of FDA-approved drug targets are rhythmic in at least one tissue," says Ludovic Mure, a Salk staff scientist and first author on the paper. "In addition to the drug target, many other mechanisms that affect drug efficiency or toxicity, like its absorption, metabolization and excretion, may be modulated by the circadian clock."

The Salk team's gene expression atlas could also help scientists illuminate how late-night lifestyles impact human health. This could apply to shift workers or anyone who deviates regularly from the day/night cycle. In addition, this work might also advance aging studies, as these rhythms often become disrupted as people grow older.

"This is a list of how genes are differentially expressed in different organs, and that will give us a framework to understand if shift work and other disruptions change how genes are expressed," said Panda. "For earlier circadian rhythm research, we did not have a reference, so this is like having a human reference genome."
-end-
Other authors on the paper were Hiep Le, Giorgia Benegiamo, Max Chang and Luis Rios of Salk; Ngalli Jillani, Ngotha Maini and Thomas Kariuki of the National Museums of Kenya; and Ouria Dkhissi-Benyahha of the University of Lyon and INSERM.

The work was supported by a Salk Institute innovation grant, the Department of Defense, the Chapman Foundation and the Helmsley Charitable Trust, the Glenn Center for Aging Research, and the Fyssen and Catharina Foundations.

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

Salk Institute

Related Genes Articles:

Are male genes from Mars, female genes from Venus?
In a new paper in the PERSPECTIVES section of the journal Science, Melissa Wilson reviews current research into patterns of sex differences in gene expression across the genome, and highlights sampling biases in the human populations included in such studies.
New alcohol genes uncovered
Do you have what is known as problematic alcohol use?
How status sticks to genes
Life at the bottom of the social ladder may have long-term health effects that even upward mobility can't undo, according to new research in monkeys.
Symphony of genes
One of the most exciting discoveries in genome research was that the last common ancestor of all multicellular animals already possessed an extremely complex genome.
New genes out of nothing
One key question in evolutionary biology is how novel genes arise and develop.
Good genes
A team of scientists from NAU, Arizona State University, the University of Groningen in the Netherlands, the Center for Coastal Studies in Massachusetts and nine other institutions worldwide to study potential cancer suppression mechanisms in cetaceans, the mammalian group that includes whales, dolphins and porpoises.
How lifestyle affects our genes
In the past decade, knowledge of how lifestyle affects our genes, a research field called epigenetics, has grown exponentially.
Genes that regulate how much we dream
Sleep is known to allow animals to re-energize themselves and consolidate memories.
The genes are not to blame
Individualized dietary recommendations based on genetic information are currently a popular trend.
Timing is everything, to our genes
Salk scientists discover critical gene activity follows a biological clock, affecting diseases of the brain and body.
More Genes News and Genes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Debbie Millman: Designing Our Lives
From prehistoric cave art to today's social media feeds, to design is to be human. This hour, designer Debbie Millman guides us through a world made and remade–and helps us design our own paths.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Insomnia Line
Coronasomnia is a not-so-surprising side-effect of the global pandemic. More and more of us are having trouble falling asleep. We wanted to find a way to get inside that nighttime world, to see why people are awake and what they are thinking about. So what'd Radiolab decide to do?  Open up the phone lines and talk to you. We created an insomnia hotline and on this week's experimental episode, we stayed up all night, taking hundreds of calls, spilling secrets, and at long last, watching the sunrise peek through.   This episode was produced by Lulu Miller with Rachael Cusick, Tracie Hunte, Tobin Low, Sarah Qari, Molly Webster, Pat Walters, Shima Oliaee, and Jonny Moens. Want more Radiolab in your life? Sign up for our newsletter! We share our latest favorites: articles, tv shows, funny Youtube videos, chocolate chip cookie recipes, and more. Support Radiolab by becoming a member today at Radiolab.org/donate.