How pervasive are circadian oscillations?

Abstract

Circadian oscillations play a critical role in coordinating the physiology, homeostasis, and behavior of biological systems. Once thought to only be controlled by a master clock, recent high-throughput experiments suggest many genes and metabolites in a cell are potentially capable of circadian oscillations. Each cell can reprogram itself and select a relatively small fraction of this broad repertoire for circadian oscillations, as a result of genetic, environmental, and even diet changes.

Keywords: circadian metabolome; circadian rhythms; circadian transcriptome; clock; coupled oscillators; oscillatory patterns.

Figure 1

(A) Examples of oscillating transcripts and metabolites from liver comparing high-fat and normal-chow fed mice. Clock, a core circadian regulator, shows a shift in phase. Srebf1, a key transcription factor regulating enzymes involved in lipid synthesis, shows a robust new oscillation only in the high-fat condition. Fgd6 shows a significantly altered oscillatory pattern. Nicotinamide Adenine Dinucleotide (NAD+) oscillates in the normal-chow condition, but not in the high-fat condition. Uracil and Uridine, which metabolically co-react, show a slight change in phase, and a significant dampening in amplitude. (B) 1. A cycle between three molecular species with an even number of negative interactions. Increasing the concentration of A, increases the concentration of B, which increases the concentration of C, which further increases the concentration of A (and vice versa if the concentration of A is decreased). Thus in general such a system does not oscillate and will tend to converge to one of several fixed-point attractors (e.g. all concentrations are high or all concentrations are low). 2. A cycle between three molecular species with an odd number of negative interactions. Increasing the concentration of A, increases the concentration of B, which decreases the concentration of C, which then decreases the concentration of A. Thus such a system will tend to oscillate. 3. Example of two interlocked cycles sharing one positive edge (between B and C) with fixed-point attractors. Changing the sign of the shared interaction creates two oscillatory cycles.