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(Re)inventing the circadian feedback loop

Steven A Brown1, Elzbieta Kowalska, Robert Dallmann

  • 1Institute of Pharmacology and Toxicology, University of Zürich, Zurich, Switzerland. steven.brown@pharma.uzh.ch

Developmental Cell
|March 17, 2012
PubMed

Insights

Circadian clocks may be simpler than previously thought. New research suggests complex timekeeping evolved from basic feedback loops, challenging the long-held transcription-translation model.

Area of Science:

  • Chronobiology
  • Molecular Biology
  • Genetics

Background:

  • For two decades, circadian clocks were primarily understood through transcription-translation feedback loops.
  • Recent discoveries highlight posttranslational circadian oscillators across various species, necessitating a paradigm shift.

Purpose of the Study:

  • To review self-sustained clock mechanisms.
  • To propose simpler minimum requirements for diurnal timekeeping compared to free-running circadian oscillators.
  • To explore the evolutionary origins of complex circadian timekeeping.

Main Methods:

  • Literature review of existing research on circadian clock mechanisms.
  • Analysis of feedback loop structures in canonical and novel circadian oscillators.
  • Theoretical modeling of timekeeping requirements.

Main Results:

  • Canonical circadian clocks involve intricate interlocked feedback loops with numerous proteins.
  • Minimum requirements for basic diurnal timekeeping may be less complex than free-running oscillators.
  • Complex circadian timekeeping might have evolved from simpler, independent feedback loops.

Conclusions:

  • The traditional view of circadian clocks solely based on transcription-translation needs reevaluation.
  • Posttranslational oscillators represent a significant addition to our understanding of circadian biology.
  • Evolutionary pathways suggest complex circadian systems may arise from simpler, interconnected timekeeping modules.

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