Gene identified in people who need little sleep
by Tianna Hicklin, Ph.D./National Institutes of Health
Getting enough sleep is important for good health and well-being. The amount of sleep you need changes as you age, and sleep needs vary from person to person. Most adults need to sleep seven or more hours each night. Not getting enough sleep can lead to physical and mental health problems.
Healthy sleep involves not only getting enough hours of sleep, but sleeping at the right time of day and having good quality sleep. Good quality sleep means that you’ve gotten enough of two different phases of sleep: rapid eye movement (REM)—the deep sleep in which dreaming happens—and non-REM. You may not be getting quality sleep if you don’t feel rested after you’ve slept enough, you repeatedly wake up during the night, or you experience symptoms of sleep disorders, like snoring or gasping for air.
Previous studies have led to the identification of over 50 families with people who need less than six and a half hours of sleep a night to feel well rested. To better understand why some people need much less sleep than most, a team led by Dr. Ying-Hui Fu and Dr. Louis Ptáček at the University of California, San Francisco carried out a study in a family with three generations of naturally short sleepers to look for genes involved in their unusual sleep patterns. The research was supported in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS). Results were published online on August 28, 2019, in Neuron.
Using whole exome genome sequencing, the researchers searched for gene mutations that only the naturally short sleepers had. They found a rare mutation in the ADRB1 gene that was being passed through the family. Family members who inherited one copy of this mutant gene had a shortened sleep cycle. The ADRB1 gene codes for the β1-adrenergic receptor. Adrenergic receptors are found on many cells in the body and respond to hormones, including those known to regulate the sleep/wake cycle.
The researchers found that certain brain cells expressed high levels of the β1-adrenergic receptor. These cells were located in a brain region that’s involved in regulating sleep behaviors called the dorsal pons. The brain cells were active when mice were in REM sleep or awake, but not during non-REM sleep.
To learn more about the mutation’s effects in the brain, the researchers created genetically engineered mice with the altered gene. Mice with the genetic mutation slept almost an hour less each day than normal mice. They had about seven minutes less of REM sleep and 53 minutes less of non-REM sleep.
Brain cells with the ADRB1 mutation showed altered activity and electrophysiological properties, making them more easily activated. Mice with the mutation showed increased activity of brain cells with the β1-adrenergic receptor compared with normal mice.
When researchers turned on brain cells with the β1-adrenergic receptor during non-REM sleep using a light-activated protein, the mice woke up. These results suggest that increased activity of wake-promoting brain cells may be one of the mechanisms underlying naturally shorter sleep cycles.
“Sleep is complicated,” Ptáček explains. “We don’t think there’s one gene or one region of the brain that’s telling our bodies to sleep or wake. This is only one of many parts.”
“Natural short sleepers experience better sleep quality and sleep efficiency,” Fu says. “By studying them, we hope to learn what makes for a good night’s sleep, so that all of us can be better sleepers leading happier, healthier lives.”