Imagine observing a plant moving its leaves up and down throughout the day. During the night they are in a fully upright position while during the day they move downward, avoiding excessive light. Intuitively, we might think that this is simply a reaction to light, but now imagine placing the plant inside a box, which is completely isolated from the outside environment. What do you expect will happen? If it is simply responding to light, there should be no leaf movements within the box. In the 18th century the French astronomer de Mairan found that, surprisingly, the leaves continue to go up and down with a rhythm of approximately 24 h (1). This is exciting because it means that the plant has a rhythm of its own, which is very close to the duration of the day. Such internally generated cycles are now known to occur in most organisms and, because they take around one day to complete a full cycle, they have been called circadian rhythms (from the Latin circa – around and diem – day).
Circadian rhythms are intriguing not just because of their duration – they have special properties.
The near 24 h cycles can be maintained so precisely that they are said to be generated by a circadian clock. If the temperature inside the box was set to 20 ºC, the plant would still move its leaves up and down with the same timing as if the temperature was adjusted to 30 ºC. This is incredible because all the functioning of living organisms is based on chemical reactions, which would typically double in speed with this 10 ºC increase. Scientists are still trying to understand how such a constant speed can be maintained and named this property “temperature compensation”.
What if you are placed in a completely isolated room, with sufficient food and no reference of external time, when would you sleep and wake up? As the plant, you would continue to be awake and asleep every 24 h or so. In fact, humans have an inner rhythm, which is slightly longer than 24 h so, in comparison to external time, you would wake up a little later every day. After leaving the room you would eventually synchronize your sleeping schedule to the actual time of the day again. It is as if you have your own internal time keeping mechanism which is adjusted by the environment every day, so it does not run late.
Circadian clocks orchestrate many biological functions, generating other circadian rhythms, and can be adjusted by specific signals as light, temperature, food or even social cues. This allows the organism to synchronise with the environment and enables it to anticipate predictable periodic changes, which are not restricted to daily cycles. Flowering time, migrations, spawning and meeting mates may all be coordinated by sensing rhythms such as seasons, phases of the moon and tides. Since timing is important for the majority of living beings, these clocks are widespread – they are found even in one of the most ancient life forms known: cyanobacteria. Cyanobacteria are bacteria that perform photosynthesis, using light as a source of energy. Therefore, it is probably advantageous to anticipate the sunrise by gearing up the photosynthetic machinery and activating cell defense mechanisms before ultraviolet levels get too high. This could be why circadian clocks came about in the first place, but interestingly they seem to have evolved again and independently in multicellular organisms, such as plants, fungi and animals (2).
Research has been carried out for over 50 years seeking what constitutes these time-keeping mechanisms and where they would be located.
In humans and other mammals, a region in the brain called the suprachiasmatic nucleus (SCN) is thought to be a central pacemaker that receives light signals from the eyes and sets the time of other cells in the body, enabling parts that have no direct information from the outside to coordinate amongst themselves and with the environment. It is composed of about 20,000 neurons grouped in two roundish structures which show near-24 h oscillations of electrical activity. Not only can the SCN as a whole generate its own rhythm but, if isolated, so does each of its nuclei and even each neuron alone (3).
With the advent of molecular biology, it was possible to show that almost every single cell in your body has its own clock, formed by the so-called clock genes, and the proteins that are produced based on them. The way these proteins interact with each other creates a cycle of accumulation, modification and destruction, which has all of the special properties of circadian rhythms and is thought to be their ultimate origin. It is tempting to consider the DNA as the root of all rhythms, but breathtaking studies have shown nature to be more complex (4). SCN neurons that were stripped down of one clock gene show no detectable circadian rhythm alone but, when connected together, the interaction restores the rhythmicity in each of them and in the tissue as a whole (5). In appropriate conditions, even without the presence of DNA, key proteins can generate circadian oscillations by themselves. As a matter of fact, scientists managed to recreate circadian rhythms using only three types of cyanobacteria clock proteins, without their genes, and providing energy (ATP) in a test tube (6)! One type of these proteins is progressively modified and then returns to the unmodified state nearly every 24 h, keeping this speed in a wide range of temperatures. This remarkable discovery was followed by other evidence that a clock can arise even in the absence of DNA, as in red blood cells (7) (that have no DNA) and a green algae (8).
It is truly amazing that a 24 h biological clock capable of maintaining speed and synchronizing to the environment can arise in so many different contexts and levels of organization. This complex choreography of living matter poses a challenge to science for years to come, but brings immediate wonder even if simply in the poetry of life re-creating the rhythms of its environment within itself.
For further reading
Implications of circadian rhythms to human health as in jet-lags, shift-work and cancer: Reddy AB & O’Neill JS. (2010) Healthy clocks, healthy body, healthy mind. Trends in Cell Biology 20(1):36–44.
Comparison of the complex circadian systems across different organisms: Bell-Pedersen D et al. (2005) Circadian rhythms from multiple oscillators: lessons from diverse organisms. Nature Reviews Genetics 6(7):544–56.
McClung CR (2006) Plant circadian rhythms. The Plant cell 18(4):792–803.
Rosbash M (2009) The implications of multiple circadian clock origins. PLoS Biology 7(3):e62.
Dibner C, et al. (2010) The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annual Review of Physiology 72:517–549.
O’Neill JS (2009) Circadian clocks can take a few transcriptional knocks. The EMBO Journal 28(2), 84–5.
Liu AC, et al. (2007) Intercellular coupling confers robustness against mutations in the SCN circadian clock network. Cell 129(3):605–616.
Nakajima M, et al. (2005) Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro. Science 308(5720):414–415.
O’Neill JS & Reddy AB (2011) Circadian clocks in human red blood cells. Nature 469(7331):498–503.
O’Neill JS, et al. (2011) Circadian rhythms persist without transcription in a eukaryote. Nature 469(7331):554–558.
Daniel S C Damineli is a biologist from São Paulo, Brazil. An alumnus of the PhD program in Computational Biology at Instituto Gulbekian de Ciência, he is now a postdoctoral researcher at the University of Maryland in the department of Cell Biology and Molecular Genetics.