Circadian Rhythm Genetics


Circadian clocks drive cyclic changes in behavior, physiology and metabolism, have a periodicity of about 24 h, and are entrained to the earthly day–night cycle by light. The circadian oscillator is composed of an autoregulatory feedback loop of clock genes that positively and negatively affect their own transcription levels and each other's.

Keywords: circadian rhythms; biological clock; oscillators; cyclic gene expression; genetic disorder

Figure 1.

The bar above the each schematic represents the light‐regime, in which t=0 h corresponds to the start of the light period. A and B: schematic actograms representing the running wheel activity of a rodent. The shaded area corresponds to the time when light is off. In constant darkness (DD), the behavioral activity is free‐running and the period length (tau, τ) can be calculated from the slope of the line traced along the onset of activity. Depending on the moment of exposure, a light pulse (indicated by a star in actogram B) can phase‐shift the rhythm. C: graphic representation of a phase response curve (PRC). A PRC can be obtained by sequentially giving light pulses at different times and plotting the phase shift. The x axis represents the time of the day, and the y axis the magnitude of the phase shift induced by a light pulse given at different times (positive values correspond to advances and negative values to delays). The numbers refer to the time of the light pulse of the examples given in actogram B (1 corresponds to a maximal phase delay, 2 to a maximal phase advance, and 3 to no shift).

Figure 2.

Molecular oscillators are composed of interlocked negative and positive transcription–translation feedback loops. Schematic of the molecular mechanism of circadian oscillator of (a) Drosophila and (b) mammals. Flags represent transcription initiation and the black bars symbolize E‐box promoter elements. Transcription repression is indicated by an interrupted line; arrows with a plus sign indicate transcription activation. Labeled rectangles and solid forms represent genes and protein products, respectively; CCG: clock‐controlled genes; U: Ubiquitin moiety; P: phosphate moiety; P (in diamond): PER; T: TIM; Cyc: Cycle; CLK: Clock; DBT: double‐time; B: Bmd1; C: Cry1/2; 1: Par1; 2: Par2; 3: Par3. For a description of the mechanism, see the text.



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Further Reading

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Wang GK and Sehgal A (2002) Signaling components that drive circadian rhythms. Current Opinion in Neurobiology 12: 331–338.

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van der Horst, Gijsbertus TJ, and Chaves, Inês(Jan 2006) Circadian Rhythm Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005970]