Although many genetic studies have focused on the circadian rhythm, few have targeted the specific genes that regulate how much sleep our bodies require.
Now, by studying a family with several members who require significantly less sleep than the average person, researchers from the University of California, San Francisco (UCSF) have identified a new gene they believe has a direct impact on how much someone sleeps. Then they tested their findings on mice.
“It’s remarkable that we know so little about sleep, given that the average person spends a third of their lives doing it,” said Dr. Louis Ptáček, a neurologist at UCSF, and one of the paper’s two senior authors.
“This research is an exciting new frontier that allows us to dissect the complexity of circuits in the brain and the different types of neurons that contribute to sleep and wakefulness.”
The family whose DNA led to the identification of this gene is one of several that Ptáček and UCSF geneticist Dr. Ying-Hui Fu, the paper’s other senior author, are studying and includes several members who function normally on only six hours of sleep. The gene, ADRB1, was identified using genetic linkage studies and whole-exome sequencing, which revealed a novel and very rare variant.
First, the researchers investigated the role of the gene variant by studying its protein in the test tube. They discovered that the gene codes for a certain type of adrenergic receptor and that the mutant version of the protein is much less stable, altering the receptor’s function.
The researchers then conducted a number of experiments in mice carrying a mutated version of the gene. They found that these mice slept on average 55 minutes less than regular mice. (Humans with the gene sleep two hours less than average.)
Ptáček acknowledges some limitations of using mice to study sleep. One of these is that mice exhibit different sleep patterns than humans, including, for example, sleeping in shorter bouts, rather than in a single continuous period.
“But it’s challenging to study sleep in humans, too, because sleep is a behavior as well as a function of biology,” he says. “We drink coffee and stay up late and do other things that go against our natural biological tendencies.”
The investigators plan to study the function of the ADRB1 protein in other parts of the brain. They also are looking at other families for additional genes that are likely to be important.
“Sleep is complicated,” Ptáček says. “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.”
Fu adds that the work may eventually have applications for developing new types of drugs to control sleep and wakefulness.
“Sleep is one of the most important things we do,” she says. “Not getting enough sleep is linked to an increase in the incidence of many conditions, including cancer, autoimmune disorders, cardiovascular disease and Alzheimer’s.”
Their findings are published in the journal Neuron.
Source: Cell Press