Circadian biology: clocks within clocks

A small cluster of approximately 20,000 neurons in the ventral hypothalamus provide the body with key time-keeping signals and drive circadian rhythms. This circadian clock exhibits surprisingly complex substructures, with inputs from the retina, and outputs to other brain structures. Rather little is known of the neurotransmitters involved, or their regulation.     

Circadian clocks: translation

One of the big questions in biological rhythms research is how a stable and precise circa-24 hour oscillation is generated on the molecular level. While increasing complexity seemed to be the key, a recent report suggests that circa-24 hour rhythms can be generated by just four molecules incubated in a test tube.     

Circadian clocks in prokaryotes

Prokaryotes have long been thought incapable of expressing circadian (daily) rhythms. Recently, however, such biological 'clocks' have been discovered in several species of cyanobacteria. These endogenous timekeepers control gene expression on a global level in cyanobacteria. Even in cyanobacterial cultures that are growing with average doubling times more rapid than one per 24 h, the circadian clock controls gene expression and cell division. We have isolated mutants of the cyanobacterial circadian pacemaker and are currently characterizing the loci responsible for their altered period phenotypes.     

Circadian biology: clocks for the real world.

The circadian system of Neurospora crassa includes a molecular feedback loop that is entrainable by light. A recent study has shown that a second, elusive oscillator interacts with the feedback loop to drive output rhythms.     

Circadian biology: fibroblast clocks keep ticking

Real-time cellular imaging of gene expression has revealed that fibroblasts contain a robust, self-sustained and cell-autonomous circadian oscillator, with a range of properties that both overlap and contrast with those of the neural clock of the suprachiasmatic nuclei.     

Circadian clocks: Omnes viae Romam ducunt

The circadian clock in all organisms is so intimately linked to light reception that it appears as if evolution has simply wired a timer into the mechanism that processes photic information. Several recent studies have provided new insights into the role of light input pathways in the circadian system of Arabidopsis.     

Circadian rhythms: biological clocks work in phospho-time

The 24 hour molecular oscillator requires precisely calibrated degradation of core clock proteins, like PERIOD. New studies shed light on a sequential series of PERIOD phosphorylation events that first inhibits, then accelerates PERIOD degradation.     

Circadian clocks in the mammalian brain

Daily cycles in physiology and behaviour are probably a universal feature of multicellular organisms. These rhythms are predominantly driven by endogenous clocks with a periodicity approximating to one day, i.e. circadian. In mammals, the circadian clock governing activity/ rest, neuroendocrine and autonomic rhythms lies in the hypothalamus, in the suprachiasmatic nuclei (SCN). Intrinsic circadian oscillators are also present in the retina. The SCN "clockwork" is based on a cell autonomous, genetically determined mechanism. Mammalian homologues of a number of Drosophila genes which encode elements of the fly circadian mechanism have recently been identified. In Drosophila, the protein products of these genes interact in a negative feedback loop, establishing a circadian cycle in gene expression. Characterisation of the roles played by putative mammalian clock genes in the SCN, and how the emergent cellular signal imposes order over the entire neuraxis, will provide a fundamental contribution to our understanding of the molecular basis of behaviour. BioEssays 22:23-31, 2000.     

Circadian clocks and adaptation in Arabidopsis

Endogenous circadian rhythms are almost ubiquitous among organisms from cyanobacteria to mammals and regulate diverse physiological processes. It has been suggested that having an endogenous circadian system enables an organism to anticipate periodic environmental changes and adapt its physiological and developmental states accordingly, thus conferring a fitness advantage. However, it is hard to measure fitness directly and there is, to date, only limited evidence supporting the assumption that having a circadian system can increase fitness and therefore be adaptive. In this article, we report an evolutionary approach to examine the adaptive significance of a circadian system. By crossing Arabidopsis thaliana plants containing mutations that cause changes in circadian rhythms, we have created heterozygous 'Mother' (F1) plants with genetic variance for circadian rhythmicity. The segregating F2 offspring present a range of circadian rhythm periods. We have applied a selection to the F2 plants of short and long T-cycles under different competition strengths and found that the average phenotype of circadian period of the resulting F3 plants show a strong positive correlation with the T-cycle growth conditions for the competing F2 plants. Consistent with their circadian phenotypes, the frequency of long-period alleles was altered in the F3 plants. Our results show that F2 plants with endogenous rhythms that more closely match the environmental T-cycle are fitter, producing relatively more viable offspring in the F3 population. Thus, having a circadian clock that matches with the environment is adaptive in Arabidopsis.     

Circadian clocks are resounding in peripheral tissues

Circadian rhythms are prevalent in most organisms. Even the smallest disturbances in the orchestration of circadian gene expression patterns among different tissues can result in functional asynchrony, at the organism level, and may to contribute to a wide range of physiologic disorders. It has been reported that as many as 5%-10% of transcribed genes in peripheral tissues follow a circadian expression pattern. We have conducted a comprehensive study of circadian gene expression on a large dataset representing three different peripheral tissues. The data have been produced in a large-scale microarray experiment covering replicate daily cycles in murine white and brown adipose tissues as well as in liver. We have applied three alternative algorithmic approaches to identify circadian oscillation in time series expression profiles. Analyses of our own data indicate that the expression of at least 7% to 21% of active genes in mouse liver, and in white and brown adipose tissues follow a daily oscillatory pattern. Indeed, analysis of data from other laboratories suggests that the percentage of genes with an oscillatory pattern may approach 50% in the liver. For the rest of the genes, oscillation appears to be obscured by stochastic noise. Our phase classification and computer simulation studies based on multiple datasets indicate no detectable boundary between oscillating and non-oscillating fractions of genes. We conclude that greater attention should be given to the potential influence of circadian mechanisms on any biological pathway related to metabolism and obesity.     

Circadian and solar clocks interact in seasonal flowering

The plant maintains a 24‐h circadian cycle that controls the sequential activation of many physiological and developmental functions. There is empirical evidence suggesting that two types of circadian rhythms exist. Some plant rhythms appear to be set by the light transition at dawn, and are calibrated to circadian (zeitgeber) time, which is measured from sunrise. Other rhythms are set by both dawn and dusk, and are calibrated to solar time that is measured from mid‐day. Rhythms on circadian timing shift seasonally in tandem with the timing of dawn that occurs earlier in summer and later in winter. On the other hand, rhythms set to solar time are maintained independently of the season, the timing of noon being constant year‐round. Various rhythms that run in‐phase and out‐of‐phase with one another seasonally may provide a means to time and induce seasonal events such as flowering.