Temperature compensation and temperature sensation in the circadian clock

Abstract

All known circadian clocks have an endogenous period that is remarkably insensitive to temperature, a property known as temperature compensation, while at the same time being readily entrained by a diurnal temperature oscillation. Although temperature compensation and entrainment are defining features of circadian clocks, their mechanisms remain poorly understood. Most models presume that multiple steps in the circadian cycle are temperature-dependent, thus facilitating temperature entrainment, but then insist that the effect of changes around the cycle sums to zero to enforce temperature compensation. An alternative theory proposes that the circadian oscillator evolved from an adaptive temperature sensor: a gene circuit that responds only to temperature changes. This theory implies that temperature changes should linearly rescale the amplitudes of clock component oscillations but leave phase relationships and shapes unchanged. We show using timeless luciferase reporter measurements and Western blots against TIMELESS protein that this prediction is satisfied by the Drosophila circadian clock. We also review evidence for pathways that couple temperature to the circadian clock, and show previously unidentified evidence for coupling between the Drosophila clock and the heat-shock pathway.circadian clock | temperature compensation | mathematical models C ircadian rhythms are daily oscillations in gene expression and protein concentration that regulate sleep (1, 2), metabolism (3,4), and a host of other biological processes (5-8). Circadian oscillations are known to be present in nearly all animals and plants, as well as some fungi and bacteria (9). In all organisms in which circadian oscillations have been observed, circadian oscillations satisfy three defining properties (10). First, circadian oscillations are self-sustained and spontaneously maintain a period of about 24 h. Second, the circadian rhythm is sensitive to light and temperature and can be synchronized to external oscillations in the quantity of either. Third, the period of the circadian oscillation is "temperature-compensated"; that is, the endogenous period of the oscillation is relatively insensitive to temperature.The genetic basis of circadian clocks has been elucidated in considerable detail over the past two decades, particularly in the fruitfly Drosophila melanogaster, the mouse Mus musculus, and the bread mold Neurospora crassa (11). In Drosophila, a self-sustained circadian oscillation in neurons is generated when a pair of proteins, PERIOD (PER) and TIMELESS (TIM), dimerize and, after some delay, translocate into the nucleus, where the proteins repress their own transcription by inactivating a transcription factor dimer composed of the proteins CLOCK and CYCLE. Light sensitivity is mediated by the blue light photoreceptor CRYPTOCHROME (CRY), which upon activation binds TIMELESS and promotes TIMELESS degradation. A remarkably similar mechanism underlies circadian clocks in mouse and Neurospora. The circadian clock of cyanobacteria has also bee...

Protein sequestration versus Hill‐type repression in circadian clock models

“…5), the major difference between HT and PS models has not been reported or investigated, to our knowledge. Future work can also investigate whether PS models follow the entrainment properties [37,45,47,142,[156][157][158] or temperature compensation mechanisms [38,40,42,[159][160][161][162][163][164][165][166] identified with HT models. Furthermore, stochastic simulations of HT models commonly indicate that circadian clocks can maintain rhythms even with low numbers of molecules [167][168][169][170].…”

mir-276a strengthens Drosophila circadian rhythms by regulating timeless expression

“…It is intriguing that the mir-276a misregulation of TIM has an effect on rhythmicity with no discernable effect on timekeeping. One possibility is that this effect reflects some unknown buffering mechanism that impacts timekeeping, perhaps related to the enigmatic mechanism(s) that underlie temperature compensation (36). Because tim missense alleles originally were identified in a screen for altered circadian period, there may be a fundamental distinction between the relationship of TIM to period determination and its contribution to output gene expression and rhythmic strength (37).…”

Functional Contributions of Strong and Weak Cellular Oscillators to Synchrony and Light-shifted Phase Dynamics

“…Each oscillator is simulated using a modified version of the Goodwin model (Bliss et al, 1982;Tyson, 2002): Various versions of Goodwin-type models have been employed to study the circadian system (Ruoff et al, 2001;Cheng et al, 2009;Saithong et al, 2010;Komin et al, 2011;Leise et al, 2013;Gu et al, 2014;Kidd et al, 2015;Gu et al, 2015). The parameters for our system (see Table 1) are set so that uncoupled oscillations dampen over time toward the steady state values,…”