Basics: Biological Clock

First published on January 28, 2007

Considering I’ve been writing textbook-like tutorials on chronobiology for quite a while now, trying always to write as simply and clearly as possible, and even wrote a Basic Concepts And Terms post, I am surprised that I never actually defined the term “biological clock” itself before, despite using it all the time.

Since the science bloggers started writing the ‘basic concepts and terms’ posts recently, I’ve been thinking about the best way to define ‘biological clock’ and it is not easy! Let me try, under the fold:

A biological clock is a structure that times regular re-occurence of biochemical, physiological and behavioral events in an organism in constant environmental conditions

Perhaps the best way to explain this is to dissect the definition word-by-word, explaining my choice of words included (and those omitted) in the definition. But first, I need to make it clear that I am NOT trying to invent a new definition, or to impose my views on others. Instead, I am trying to capture the sense in which the term has actually been used by the practitioners in the field, and the way such usage may have changed over time.

What a Biological Clock isn’t

– I need to stress once again that the term “biological clock” is not a real entity, but a metaphor used by the researchers to describe a real entity in shorthand. This metaphor was very useful throughout the history of the field, though on occasion it locks people into frames of mind that may prevent them from seeing a problem as clearly as it could be.

– A biological clock is certainly not to be taken literally, as a real machine with gears or pendulums ticking somewhere inside a living organism.

– A biological clock does not refer to the pseudoscience of biorhythms, one of many ways to extract money from the gullible, either in its original Wilhelm Fliess version or its more recent and spiced-up Oriental variety.

– Colloquially, people often use the term ‘biological clock’ in the sense of “mine is ticking” meaning that time for having kids is running out. That is fine in conversation, but it is not a scientific use of the term.

– Biological Clock should not be confused with the Molecular Clock, a measure of the rate of nucleotide substitution in the DNA over evolutionary time periods, used to infer times of divergence between lineages.

…in an organism…

There are rhythms in nature that occur at levels higher than the organism, e.g., the cycles of population booms and busts in ecology (hare and lynx examples are most famous). Such rhythms are never refered to in the scientific literature as driven by any kind of clocks. The term ‘biological clock’ is sometimes used interchangeably with the term ‘physiological clock’.

This is also the reason I left out of the definition any references to adaptive or evolutionary factors and focused on the way the term is used in the literature – as a sources of a physiological mechanism.

…in constant environmental conditions…

If I give you an electroshock every two hours, you will exhibit a 2-hour cycle of convulsions. This does not mean that your rhythm is endogenously generated by an internal biological clock. It is directly induced by a recurring event in the environment. Many rhythms in living organisms are a result of a direct effect of some environmental factor. A biological clock is responsible only for recurring events that are not direct responses to the environmental cycles.

Yet, I did not use a term “environmentally independent” or some such phrase, because the rhythms generated by endogenous clocks are malleable to environmental factors, especially to light (and very few hormones and other chemicals) – the phase, period and amplitude of the rhythms can be modified by environmental cues. They just don’t disappear once the organism is held in completely constant conditions for prolonged periods of time (at least 2-3 times longer than the period of a single cycle).

…biochemical, physiological and behavioral events…

I did not want to say “everything”, although it comes close in reality. Again, this excludes ecological cycles. It also leaves it somewhat vague if developmental events are to be included or not, which is a good thing, because some developmental events are (e.g., insect eclosion, bird hatching, somite development, developmental timing in Nematodes), while others are not regulated by various types of biological clocks.

Also, not every clock in the body controls every event. A clock in the liver times events in the liver, a clock in the lungs controls events in the lungs. Only the pacemakers control everything, by synchronizing peripheral clocks, which in turn drive local rhythms.

A pacemaker in the suprachiasmatic area (SCN) of the mammalian brain may entrain other local clocks in the brain which in turn drive rhythms of various behaviors.

…times regular re-occurence…

I did not really want to use the word “rhythm” because it may suggest only rhythms of a high frequency (as in music rhythms). I also did not want to limit the definition only to daily/circadian rhythms. Other kinds of rhythms, e.g,. tidal, lunar and circannual, are also driven by biological clocks. The term “calendar” is sometimes seen in popular articles, though not as a specific scientific term, and only in reference to photoperiodism.

…a structure…

This was the hardest part of making the definition. What is a clock? A mechanism? An organ system?

Throughout the 20th century, this was easy. You take an organism, you put it in some kind of setup in which you can continuously monitor some kind of output (usually behavioral activity) and you document a rhythm in constant conditions. Then you systematically lesion or remove various organs or nuclei in the brain, until the rhythm disappears. The organ, which when removed results in arrhytmicity is, you publish, the biological clock in that organism. Thus, you discover the SCN in mammals or the pineal or retina in non-mammalian vertebrates, various brain-nuclei, optic lobes or eyes in invertebrates, etc.

But the world has changed since then. We are now investigating biological clocks at the molecular level. Is the transcription-translation feedback loop among a dozen or so canonical clock genes itself a clock? No, because it is only a necessary but not sufficient part of the clock. Or is a cell that contains such a molecular mechanism a clock? I’d say yes. Or is the tissue composed of such cells a clock? Different people in the field use this term differently, so I wanted to remain vague. But it is a structure.
At the same time, the distinction between a clock and a pacemaker is becoming more and more important, yet more and more difficult to define.

The clock in each cell of the liver is entrained by the signals from the pacemaker in the SCN. The SCN is, in turn, entrained by the light-dark cycles detected in the environment by the eyes. Is the only distinction between a pacemaker and the peripheral clock in the ability to directly (vs.indirectly) tap into environmental information? Does that mean that we have pacemakers and clocks, while fruitflies and zebrafish have only pacemakers as every cell of their bodies is a pacemaker directly entrained by environment? Those are some of the current problems in the field. This is the reason why more and more chronobiologists tend to use the term “circadian system” instead of “circadian clock”, in order to imply the underlying complexity.

In many animals, there are not just clocks in every cell in the body, but also multiple pacemakers, each getting information from the environment. These multiple pacemakers affect each other as well as peripheral clocks and are also affected by the feedback from the periphery.

And that is just vertebrates! We know much less about clocks and circadian organization in invertebrates, fungi and plants.

And then, there are unicellular organisms, both bacteria and protists, many of which contain, or should we say, ARE biological clocks. There is no distinction there between the clock and everything else the cell does.

Recently, it has been discovered that biological clocks (or at least clock genes) are also directly involved in regulation of (not just timing of) development, metabolism, appetite, thermoregulation, reproduction, sleep, cocaine addiction and behavior. Thus, the borderlines between the circadian system and other organ systems are getting increasingly fuzzy.

So, whatever structure (cell or higher) that controls the timing of oscillations in everything happening in the body devoid of environmental cues is a biological clock.

Related reading:

Circadian clock without DNA–History and the power of metaphor
Everything You Always Wanted To Know About Sleep (But Were Too Afraid To Ask)
Seasonal Affective Disorder – The Basics
Sun Time is the Real Time
Lesson of the Day: Circadian Clocks are HARD to shift!
Lithium, Circadian Clocks and Bipolar Disorder
Are Zombies nocturnal?
Diversity of insect circadian clocks – the story of the Monarch butterfly
Me and the copperheads–or why we still don’t know if snakes secrete melatonin at night
The Mighty Ant-Lion
City Of Light: Insomniac Urban Animals
Spring Forward, Fall Back – should you watch out tomorrow morning?
A Pacemaker Is A Network

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