Review Article | Published:

Circadian rhythms from multiple oscillators: lessons from diverse organisms

Nature Reviews Genetics volume 6, pages 544556 (2005) | Download Citation

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Abstract

The organization of biological activities into daily cycles is universal in organisms as diverse as cyanobacteria, fungi, algae, plants, flies, birds and man. Comparisons of circadian clocks in unicellular and multicellular organisms using molecular genetics and genomics have provided new insights into the mechanisms and complexity of clock systems. Whereas unicellular organisms require stand-alone clocks that can generate 24-hour rhythms for diverse processes, organisms with differentiated tissues can partition clock function to generate and coordinate different rhythms. In both cases, the temporal coordination of a multi-oscillator system is essential for producing robust circadian rhythms of gene expression and biological activity.

Key points

  • Daily rhythms in biochemical, cellular and behavioural activities are controlled by the biological clock, which consists of one or more endogenous oscillators.

  • The clock exerts its effects on a wide variety of processes, ranging from development in fungi, cell division in the marine protist Gonyaulax polyedra, photosynthesis in plants, sleep in animals, to cognitive functions in humans. Although circadian rhythms are present in different organisms, several aspects of the clock mechanism, and its complexity, are not conserved among these organisms.

  • In prokaryotic and eukaryotic microorganisms, the circadian clock system seems to consist of several oscillators. These oscillators might respond to different environmental signals and direct rhythms in specific genes and behaviours. The coupling of oscillators is thought to provide stability and precision to the timing mechanism.

  • In eukaryotes with differentiated tissues, a network of cell autonomous oscillators is found not within a single cell, but among cells in different tissue types. The clock system in eukaryotes also regulates rhythms in diverse biological processes, but these rhythms can be specific to different tissue types.

  • In mammals and birds, a circadian pacemaker in the brain responds to input from the environment and coordinates overt rhythmicity throughout the peripheral tissues.

  • In mammals, lesions and metabolic and electrophysiological studies have provided incontrovertible evidence that the SCN of the hypothalamus serves as the master circadian pacemaker. This pacemaker can coordinate rhythmicity in downstream cells and tissues.

  • In non-mammalian vertebrates, the circadian clock system seems to be more complex. In birds, the circadian system consists of at least three anatomically distinct circadian pacemakers; the retina, the pineal gland and an avian homologue of the mammalian SCN.

  • In Drosophila melanogaster, the hierarchal model of a central pacemaker setting the time of peripheral oscillators does not hold; virtually all tissues harbour circadian oscillators that can be entrained directly by light.

  • So, the need for a centralized pacemaker to entrain peripheral oscillators in organisms seems to be dependent on the ability of peripheral tissues to be directly entrained.

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Acknowledgements

The authors are members of the Center for Research on Biological Clocks at Texas A&M University, Houston, USA. The work described in this review from the authors' laboratories was funded by the US National Institutes of Health, including an NINDS Program Project Grant and an NIEHS Center Grant.

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Affiliations

  1. Center for Research on Biological Clocks, Department of Biology, Texas A&M University, College Station, Texas 77843-3258, USA.

    • Deborah Bell-Pedersen
    • , Vincent M. Cassone
    • , David J. Earnest
    • , Susan S. Golden
    • , Terry L. Thomas
    •  & Mark J. Zoran
  2. Department of Human Anatomy and Medical Neurobiology, Texas A&M University, System Health Science Center, College Station, Texas 77843-1114, USA.

    • David J. Earnest
  3. Department of Biology and Biochemistry, University of Houston, 4800 Calhoun Road, Houston, Texas 77204-5001, USA.

    • Paul E. Hardin

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Correspondence to Deborah Bell-Pedersen.

Glossary

CLOCK

A circadian clock is a 24-hour timing mechanism that is composed of molecular oscillators.

CIRCADIAN RHYTHM

A biological rhythm with a 24-hour period that persists in constant conditions.

OSCILLATOR

A system of components that interact to produce a rhythm with a definable period length. A circadian oscillator can drive a rhythmic output, but requires other oscillators (pacemakers) for its entrainment and/or function. A circadian oscillator can therefore be self-sustained, but cannot operate properly independently of other oscillators.

ENTRAINMENT

The process by which an environmental rhythm, such as the light–dark cycle, regulates the period and phase relationship of a self-sustained oscillator.

PACEMAKER

An oscillator that drives an output and/or entrains another oscillator. A circadian pacemaker is a specialized oscillator that operates independently of other oscillators to drive rhythmic outputs, either directly or through other oscillators, and is entrained by environmental cues.

SUPRACHIASMATIC NUCLEUS

A small region of the brain that sits on top of the optic chiasm in the anteroventral region of the hypothalamus. Each of the bilaterally paired nuclei that comprise the SCN contains 8,000–10,000 cells packed together.

PERIOD

The time after which a defined phase of an oscillation (such as a peak or trough) recurs.

NUCLEOID

A structure in a prokaryotic cell that is composed of chromosomal DNA and its associated chromatin-like scaffolding proteins.

PHASE

The instantaneous state of an oscillation relative to a reference point.

SUBJECTIVE MIDDAY

The portion of a circadian day that is spent in constant darkness, which corresponds to the midday phase of a light–dark cycle.

GROUP 2 SIGMA FACTORS

Members of a family of sigma factor proteins that are responsible for conferring promoter-specific contacts on the RNA polymerase enzyme of eubacteria, thereby allowing specific genes to be transcribed.

CONIDIOSPORES

Asexually produced haploid fungal spores that are formed on a specialized aerial hypha — the conidiophore — that rises above the substratum.

HUMORAL

Pertaining to elements that are dissolved in the blood or body fluid, typically serum.

HYPOTHALAMUS

The part of the brain that lies below the thalamus, forming the main portion of the ventral region of the diencephalon and functioning to regulate bodily temperature, certain metabolic processes and other autonomic activities.

SYMPATHETIC NERVOUS SYSTEM

Refers to a part of the autonomic nervous system that generally has excitatory function and regulates heart rate and blood pressure.

OPSINS

A family of visual pigments.

MALPHIGHIAN TUBULES

The part of an insect's gastrointestinal tract that excretes nitrogenous waste and maintains ionic balance.

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https://doi.org/10.1038/nrg1633

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