Genetic Difference Means Less Sleep

Length of Sleep Affected by the DEC2 Gene

by Mandi Hartman, Stanford University

September 17, 2009

Some lucky people can get by on less sleep. A new study just out might explain this difference, at least for a few people.

In the study, scientists found that people with a small difference in the DEC2 gene feel perfectly rested with only 6.5 hours of sleep a night. People with the more typical version of this single gene need about 8 hours.

This result is a little surprising because sleep is so complicated. Lots of genes all work together to cause someone to get sleepy, dream, have rapid eye movement, wake up, etc.

Usually when lots of genes are involved in something, they all contribute a bit to the behavior. If any one gene is a little different, it has a small effect.

One exception to this is genes like DEC2. DEC2 is a master regulator — it controls many other genes. In this case, DEC2 controls many different genes involved in sleep. So differences in this one sleep gene can affect lots of other sleep genes, too.

Early results suggest that this particular difference in this particular gene may not explain many cases of different sleep requirements, though. From a first pass, this difference appears to be rare.

But the study does show that it is possible to identify single DNA differences that can have big effects on behavior. And who knows, maybe studies like these can lead to safe, effective ways to get less sleep!

DEC2 Affects Sleep Time in Humans and Mice

Scientists used mice to
confirm that the P385R
version of DEC2 is why
some people need less sleep.

A group of scientists stumbled on the DEC2 gene when studying sleep behavior in a family. Two people in this family woke up very early in the morning.

Scientists compared the DNA of the early risers to the rest of the family. The researchers found that the people who needed less sleep had a version of DEC2 called P385R. The rest of the family had the more common version.

DEC2 was known to be involved in sleep based on studies in mice, so the scientist figured the rare version of DEC2 was the direct cause for shorter sleep times. But they needed to prove it.

To test the idea, the researchers compared how well normal and P385R DEC2 did their jobs. DEC2 is supposed to turn off a set of genes at certain times in the day. P385R, it turns out, isn’t as good at turning them off.

To really make sure P385R causes the short sleep times, the authors designed mice that had this version instead of the more typical one. Mice, too, stayed awake longer when they had P385R DEC2 compared to mice with the normal version.

The P385R version of DEC2 has such a strong effect that it even affected animals, like fruit flies, that don’t usually have a DEC2 gene. When researchers put P385R in flies, the flies needed less sleep too.

The researchers aren’t yet sure exactly why P385R DEC2 causes everything from flies to people to need less sleep. But they do know that DEC2 affects the internal, circadian rhythm.

The Circadian Clock Controls Waking Hours

Some genes turn on and off
on a daily schedule.

Each day, the timing and length of sleep is regulated by what’s called the circadian clock. This internal clock means that for humans, sleep happens at night when it’s dark. It also means that most people need about 8 hours of rest, usually in one big chunk.

All of this is orchestrated by a huge number of genes that all work together. Some control when to feel tired. Others control when to wake up. And others control all the other aspects of sleep.

There are known genetic disorders that affect sleep length and quality. Some of these make sleep possible only in short spurts. People who have a certain version of the Bmal1 gene sleep like this.

Other gene versions shift the cycle, either early or late, from what most people experience. Differences in the CSNK1D gene, for example, cause people to go to bed 4 hours earlier than average.

The DEC2 gene is a big part of controlling how genes like these all work together to make circadian rhythms work. It does this by controlling when these genes are turned off.

More Information

The Natural Sleep Cycle Depends on Circadian Clock Genes

Genes are not always on, and it makes sense to keep some off when they’re not needed. For example, the genes that control digestion should be off until after eating. Sleep genes, then, should be on when sleeping then turn off when it’s time to wake up.

So genes can be turned on and off rapidly and frequently. And this makes sense when thinking about sleep. Each day is a cycle, and our bodies must regulate when to wake up and when to fall asleep.

Feelings we get, such as sleepiness in the evening, and behaviors we exhibit, such as rapid eye movements during sleep, are controlled by genes. Sleep state changes depending on the time of day, each day. This means the genes that control different parts of the sleep cycle must be turned on and off to keep the cycle going.

The circadian clock genes work to control many aspects of the sleep cycle. Each is active a certain part of the day or night, depending on its specific job.

So sleepy genes are on in the evening and off in the morning. Rapid eye movement genes are on only during sleep. And so on.

Like other genes, DEC2 doesn’t really do anything on its own—it doesn’t actually turn off any genes. The DEC2 gene has the instructions for making the DEC2 protein. And it is this protein that shuts off certain sleep genes.

Genes are Pieces of DNA that Have Specific Jobs

DEC2 P385R makes a protein that
doesn't shut genes off as well
as the usual version.

Each gene has the instructions for making a particular protein. It most cases, the protein is what actually carries out a gene’s job.

One gene might have the instructions for a protein involved in digesting the sugar found in milk. Another might have the instructions for making pigment to color a person’s eyes. Another might be used to make someone’s eyes move rapidly during sleep. And so on.

To make a protein from a gene, a cell must first read that gene*. Transcription factors (TFs) are proteins that affect the reading process of genes.

These TFs can either make it easier or harder for a cell to read a gene. DEC2 makes the reading harder for a whole bunch of genes.

Imagine a gene as a light switch. When it’s on, it’s being read and making protein. The switch needs to be flipped up at certain times depending on the gene’s job.

Other times it needs to be off. Transcription factors like DEC2 act like a piece of tape holding the switch down. The tape would need to be removed to turn on the switch. Just like DEC2 covers up its targets when they need to be off.

The P385R version of DEC2, then, is like a piece of tape that has lost its stickiness. If P385R doesn’t stick as well, it’s not as good at turning off those genes. This results in people with the P385R version needing less sleep.

Even though the researchers made a strong connection between DEC2 and sleep time, they did not delve into just exactly why the rare version can’t do its job as well. Future work will be needed to figure out how one gene can have such a big effect on sleeping.

As scientists continue studying sleep genes, a better understanding of how genetics affect this complex behavior will emerge. This will help not only for figuring out sleep is normally controlled, but also what might be wrong when sleep problems occur.

* Reading a gene involves two processes. The first is called transcription. This is when the DNA is copied into RNA. The second step is called translation. This is where the cell reads the RNA and makes a protein.

Mandi Hartman

More Information

Understanding genes and proteins

Content provided by the Department of Genetics, Stanford University.