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been growing progressively clearer over the last decade. Studies of the
molecular basis of circadian rhythms now use gene chip technology
to determine what genes exhibit circadian or otherwise rhythmic
temporal expression patterning at the level of systemwide phenomena.
The use of gene chips will be discussed in the next chapter.
Both TIM and PER are made during the day, with the levels of TIM
and PER proteins rising to a peak in early evening. TIM binds PER and
the TIM/PER complex enters the nucleus and inhibits the action of
another set of proteins, dCLK and CYC. These proteins are the products
of the dClock (dClk) and cycle (cyc) genes, and they are transcription
factors. In the absence of the TIM/PER complex, the dCLK and CYC
proteins bind to each other and then bind to the controlling regions of
the per and tim genes, turning on their expression so that per and tim
mRNAs, and then proteins, are made. But when the TIM/PER complex
enters the nucleus, it interferes with the ability of the dCLK/CYC
complex to promote transcription of tim and per mRNA, so the
transcription of tim and per mRNA stops. Both TIM and PER will be
degraded by morning, the dCLK/CYC complex will bind to the tim and
per genes and turn them on, and the amounts of tim and per mRNA,
and then protein, will rise.
This cyclic behavior of mRNAs and proteins gives rise to the circadian
rhythm of the fly. There are mammalian homologues of all of these
genes, and their mRNAs and proteins undergo similar cyclic behaviors.
Generally speaking, the more important a gene is, the more highly
conserved it is. The extraordinary conservation of these genes across
such diverse species indicates the powerful selective advantage
conveyed by the circadian system.
The following works can be recommended for additional information
on the identification of circadian genes: Panda et al. (2002), Reppert
and Weaver (2002), Richter et al. (2004), and Bell-Pedersen et al. (2005).
E. Studying Circadian Phenomena with Per-Luc Bioluminescence
It is now well established that circadian timing control exists in
effectively every cell of an organism. Current research is directed at
determining how these numerous, widely distributed, rhythmic cells are
orchestrated within the overall circadian mechanism. The challenge is to
understand how the molecular and cellular circadian machinery
produces the complex circadian behaviors manifested at the levels of
tissues, organs, and whole organisms.
Circadian timing systems can be viewed as having a master clock in
the brain and subsidiary clocks in other tissues. Experiments
investigating communication between these levels are essential. In the
SCN, this entails making observations of the electrical activities
of individual neurons, as well as the collective electrical activities of
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