What is a circadian clock?

Broadly speaking, the circadian clock is a cell and molecular feedback loop – inside the cell, a bunch of proteins that interact with genes and DNA, which in turn interact back with those original proteins. This cellular feedback loop controls those outward and apparent rhythms we are aware of, like jet lag and waking, as well as many more we may be unfamiliar with, but it isn’t just humans who have a body clock, all life on planet Earth has one, although its workings aren’t exactly the same in all life-forms.

The feedback loop. Proteins join together to activate gene transcription of genes that subsequently repress the original proteins. This feedback generates oscillations of gene expression.
The feedback loop. Proteins join together to activate gene transcription of genes that subsequently repress the original proteins. This feedback generates oscillations of gene expression. From Eckel-Mahan and Sassone-Corsi, 2013, Metabolism and the circadian clock converge.

In animals, the key players are genes called clock, bmal, period and cryptochrome. There are actually multiple versions of the genes, named numerically (clock1a, bmal2, period3 etc) and shortened to 3 or 4 letters (clk1a, bmal2, per3 etc). To explain the cycle, we need to start with clock and bmal and go twice around the feedback loop, each stage showing the effect of the previous.

Firstly, CLOCK and BMAL proteins (CLK and BMAL; by consensus gene names are in italics and PROTEIN names are in uppercase), interact in the cell, joining together to turn on period and cryptochrome genes. As the genes are turned on, they are transcribed by the cell, eventually begetting proteins, PER and CRY proteins. These proteins interact with CLK and BMAL proteins to make CLK and BMAL less activating, repressing CLK and BMAL.

Secondly, as CLK and BMAL are now repressed, the turning on of period and cryptochrome genes is stopped. Fewer PER and CRY proteins are generated by the cell. Fewer PER and CRY proteins means less repression of CLK and BMAL, and so CLK and BMAL are released to begin another cycle.

The overall effect is similar in plants and other organisms: Activator proteins turn on repressor genes, these repressor genes are translated into repressor proteins by the cell and repress the activator proteins and so on. These proteins and genes in the clock aren’t the same in all organisms, but they play similar roles turning on or off genes, modifying the activity of proteins, like how David de Gea and Manuel Neuer are not the same player, but play similar roles for their teams. The fact that clocks have a similar feedback mechanism but consist of different components in the different branches of life adds to the idea that circadian clocks must be evolutionarily adaptive. It is an example of convergent evolution, where two separate species look similar without being evolutionarily related, such as how dolphins and sharks look fairly similar and are adapted to the broadly similar environments but are completely different species. In this case, evolution has dictated that the best body shape for fast and efficient swimming in water is a streamlined oval. In the case of circadian clocks, we can suggest that evolution has dictated that the best way of organising your physiology and behaviour is through the use of a molecular feedback loop which acts within the cells of the body.

 

Two illustrations of how the molecular components make up the circadian clock. On the left - in zebrafish. Clock (CLK) and bmal (BMAL) proteins (there are 6 versions) interact to activate (green arrow) transcription of per and cry genes. PER and CRY proteins then interact with CLK and BMAL to repress (green line with flat on top) their activity. Per and cry are also activated by light. On the right - plants. CCA1 and LHY are the CLK and BMAL equivatlents, interacting to activate PRR7 and PRR9 which then repress CCA1 and LHY.
Two illustrations of how the molecular components make up the circadian clock. On the left – in zebrafish. Clock (CLK) and bmal (BMAL) proteins (there are 6 versions) interact to activate (green arrow) transcription of per and cry genes. PER and CRY proteins then interact with CLK and BMAL to repress (green line with flat on top) their activity. Per and cry are also activated by light. Taken from Vatine et al., 2011, It’s time to swim! Zebrafish and the circadian clock. On the right – plants. CCA1 and LHY are the CLK and BMAL equivatlents, interacting to activate PRR7 and PRR9 which then repress CCA1 and LHY. Taken from Harmer lab at UC Davis

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