MORNING BIRD OR NIGHT OWL?
THE SCIENCE AND GENETICS OF SLEEP PREFERENCES
Photo credit: Jonathan Willier
Previously on Dish on Science, we talked about how circadian rhythm works and why it’s important. This article is part of our three-part series on circadian rhythm and will focus on sleep.
Do you have that one friend who just can’t get up in the morning? Or maybe you are that friend? No judgment - I am that person. No matter how much I tell myself that getting up early is a great thing to do, I’m miserable any time before 10 a.m.
Or maybe you’re someone who wakes up bright eyed at the crack of dawn. Seriously, how do you do it?
While our behavior and environment affect our time preferences, we also have a system in our cells that influences these inclinations. It’s like a better, stronger alarm clock, and it’s wound a little different for each person. This alarm clock is called your circadian rhythm, and it determines whether 6:00 a.m. is a pleasant or terrible time of day. Most people have a circadian rhythm that’s pretty “normal” based on society’s standards; these people can adjust to a 9 to 5 schedule quite comfortably. The rest, however, are split between early birds and night owls, and their preferences can be quite extreme.
Sleep preferences are very much influenced by our DNA. Just like a real clock has many interlocking parts, our biological clock is an elegant system of genes that talk to and regulate each other. We’ll talk about how small changes in a gene or two can change someone’s sleep schedule for life, and about the recent work that scientists have done to find the genes responsible for sleep preferences.
MECHANISMS OF SLEEP
Sleep is a fairly complicated subject. Despite doing it for hundreds of millions of years, we’ve just recently started to understand why we need sleep at all! So it should come as no surprise that the the biology behind sleep is equally complex.
We know there are two parts to sleep: sleep homeostasis, and circadian rhythm. You can think of the former as the “need” to sleep, and it can sometimes override the biological clock. It’s the guiding force behind the observation that people who are sleep deprived for several days can fall asleep at any hour of the day, or “sleep in” past their usual waking hour.
In contrast, circadian rhythm tells us what times to sleep, and it doesn’t change much on a daily basis. Unless the need to sleep overwhelms us, we are awake during times of daylight and asleep after sunset in a natural cycle that lasts about 24.2 hours. 25% of people have a slightly shorter cycle, and 75% of people have a longer one, but we don’t get derailed over time because our circadian rhythm uses daylight to prevent deviations from building up. This use of daylight to “reset” the biological clock also explains how we’re able to adapt to new time zones when we travel. Special cells in our eyes relay information about light and dark through a light-sensitive chemical called melanopsin. As these cells are distinct from the cells that relay information about images, circadian rhythm also regulates itself in most people who are blind.
However, although our circadian rhythm gets synchronized to the patterns of light and dark around us, it doesn’t actually depend on light to keep going. This observation first came from an intense experiment in the 1960s, in which, for the love of science, geologist Michael Siffre lived underground for 2 months. He reported his sleep, wake, and meal times to assistants, and despite the lack of clocks and daylight, managed to keep an average day of 25 hours until the experiment was over. From this, scientists began to realize that our biological clock, despite having evolved from cycles of light and dark, can regulate itself.
At the cellular level, our biological clock regulates the release of hormones that make us drowsy (melatonin) or alert (primarily cortisol). Melatonin is usually absent during daylight hours and starts being released mid-evening. This release reaches its peak between 2:00 and 4:00 a.m., (so if we’re still awake during this time, we’re usually not very productive), then falls to the daytime low around 7:00-8:00 a.m. Cortisol, in contrast, starts being released around 6:00 a.m., usually just before a person gets up, so that it’s highest as the person is starting the day. Cortisol remains high during the day, except for a trough in the early afternoon - the source of the dreaded post-lunch slump.
DIFFERENT CLOCKS FOR DIFFERENT PEOPLE
While most people can relate to these times of alertness and drowsiness, some have extremely different biological clocks. So different, in fact, that people can be said to suffer from circadian rhythm sleep disorders. These arise when the master regulator of our biological clock gets damaged in trauma or disease, or more commonly, from mutations in circadian rhythm genes. People with advanced phase sleep disorder (APSD) find it extremely difficult to stay awake in the early evening and remain asleep until sunrise, often going to bed around 6:00 p.m. and waking up around 3:00 a.m. Those with delayed phase sleep disorder (DPSD) have the opposite problem - they have trouble sleeping early, and would prefer to sleep from 3:00 a.m. to noon. In all cases, sufferers can sleep an unbroken eight hours and feel well rested, but simply can’t choose the eight hours that are “normal.”
While APSD and DPSD can be inconvenient because of society’s standards for work and social hours, irregular sleep-wake rhythm is even harder to work around. Although total sleep time is normal, people with this disorder simply cannot predict when they will sleep or feel alert, and take naps throughout the day. So far, a “weak” circadian rhythm is thought to be the culprit; experiments in mice where the biological clock is removed has similar effects, causing mice to sleep at random times.
Finally, some blind people suffer from “non-24-hour sleep-wake disorder,” where sleep onset and wake times are delayed from day to day. This happens when the cells of the eye that perceive light are damaged, preventing the biological clock from resetting itself with daylight. People with this disorder - including sighted people, where the cause is unknown - follow their natural circadian rhythm instead of daylight hours, and it is hardly ever exactly 24 hours.
Although your circadian rhythm might make you a morning person or a night owl, you likely don’t have one of these disorders, which are quite rare. More commonly, slight variations in circadian rhythm lead to different “chronotypes,” or sleep preferences, and are still considered healthy. For example, while the research is still controversial, circadian rhythms do change as people age. Older people have an earlier sleep phase than younger people - which translates into earlier bedtimes - as well as a weaker rhythm - which translates into less restful sleep. These changes happen at a cellular level and have been interestingly attributed not to changes in the cells themselves, but to changes in the blood serum surrounding our cells.
In addition, variations in circadian rhythm can also stem from natural variations in DNA, called “single nucleotide polymorphisms” (SNPs). While we are about 99.0-99.9% alike in our DNA sequences, there are key differences that set us apart. Identifying these SNPs may help us understand circadian rhythm, and in the long run, better tailor a person’s job or lifestyle to his or her chronotype.
OF FLIES AND MEN
Initial studies on chronotype made use of a survey, designed in 1976, to get a sense of a person’s “morningness” or “eveningness.” (You may take the survey here if you don’t already know your chronotype, and the results may surprise you!) The studies then took DNA from participants and looked at the sequences of circadian rhythm genes. One elegant study linked sleep preference to the length of the Per3 (Period circadian clock 3) gene. This gene has a region that can be repeated either four or five times, and night owls more frequently have the shorter version. Another study discovered a SNP in Per1. Those with one specific SNP are more likely to wake up at an earlier hour compared to those with other genotypes.
However, while these early results were fascinating, small study sizes combined with possible biases in self-reporting limited the number of SNPs that could be found and the relevance of the findings. It was not until this year that scientists published two large-scale studies on SNPs and chronotypes in humans. Taking DNA samples and self-reported sleep preferences from ~90,000 people, the personal genomics company 23andme found 15 gene regions that predispose people to “morningness” or “eveningness.” A similar study in the UK did the same for ~100,000 people, coming up with 12 gene regions. Although each of these SNPs contributes just a little bit to a person’s preference, taken together they can predict it with accuracy.
Points for novelty, however, go toward adapting flies as a model for chronotype research. While it may seem strange to study how a fly sleeps, flies really aren’t that different from us. Just like us, they have a well established biological clock. In fact, their scientific name means “dew-loving,” a nod to their strong preference for being active at dusk and dawn, and sleeping much of the day and night. The earliest studies on circadian rhythm, including the discovery of the core clock genes, were done in flies.
Just like us, different breeds of flies have different chronotypes. These don’t show up so much in sleeping habits per se, but are more obvious in “eclosion,” the moment when flies hatch from pupal cases to become adults. Some strains, or breeds of flies, are “early birds” in that they prefer to hatch at dawn, while some are “late risers” and prefer to hatch at dusk. In a novel and recent study, instead of looking at the DNA sequences of early and late flies, scientists focused on the genes that were actively being expressed, or "turned on", as a more accurate measure of which genes were important for either chronotype. What they found was that early and late flies indeed expressed different genes. What’s more, some genes were expressed uniquely in early or late flies regardless of exposure to light, consistent with the idea that circadian rhythm regulates itself.
Yet perhaps most fascinating was the fact that very few of these genes were central clock genes. Late flies do not simply turn on genes slower than early flies; rather, they are express an entirely different set of genes. Many of these genes are involved in metabolism, early stage development, and development of the eyes. While scientists are still looking to see if this observation is true in humans, what it means is that our chronotypes might depend on more aspects of our biology than we previously thought.
Taken together, the latest sleep research in humans and flies is not only novel and interesting - it may also have implications for how we live and work. While we still need to figure out how each of the genes affects circadian rhythm - after all, the studies looked at association and not causation - scientists hope that someday we’ll put the information to good use. Perhaps we’ll be better at tailoring different jobs to people with different chronotypes, for instance, designing an evening shift for an extreme night owl. In addition, we’ll be more aware of whether an incompatible chronotype is making a person sick or unproductive. Although we can’t fully change our sleep preferences, understanding why they exist may help us adapt to them better. And maybe some of us won’t feel so bad when it’s 10 a.m. and we’re throwing the alarm against the wall.
