Circadian rhythms from multiple oscillators: lessons from diverse organisms

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.The temporal coordination of internal biological processes, both among these processes and with external environmental cycles, is crucial to the health and survival of diverse organisms, from bacteria to humans. Central to this coordination is an internal CLOCK that controls CIRCADIAN RHYTHMS of gene expression and the resulting biological activity (BOX 1). Despite disparate phylogenetic origins and vast differences in complexity among the species that show circadian rhythmicity, at the core of all circadian clocks is at least one internal autonomous circadian OSCILLATOR. These oscillators contain positive and negative elements that form autoregulatory feedback loops, and in many cases these loops are used to generate 24-hour timing circuits 1, 2 . Components of these loops can directly or indirectly receive environmental input to allow ENTRAINMENT of the clock to environmental time and transfer temporal information through output Competing interests statementThe authors declare no competing financial interests. NIH Public Access Author ManuscriptNat Rev Genet. Author manuscript; available in PMC 2009 September 1. Published in final edited form as:Nat Rev Genet. 2005 July ; 6(7): 544-556. doi:10.1038/nrg1633. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript pathways to regulate rhythmic clock-controlled gene (CCG) expression and rhythmic biological activity.Whereas a self-contained clock in single-celled organisms programmes 24-hour rhythms in diverse processes, multicellular organisms with differentiated tissues can partition clock function among different cell types to coordinate tissue-specific rhythms and maintain precision. Now that individual molecular circadian oscillators have been sufficiently described, it has become possible to go beyond single oscillators to try and understand how multiple oscillators are integrated into circadian systems. Evidence accumulated in recent years indicates that the intracellular oscillator systems of single-celled organisms might be more complex than those of higher eukaryotes, whereas the complexity of circadian outputs in multicellular organisms is an emergent property of intercellular interactions. In this review, we discuss the complexity of the circadian clocks on the basis of molecular genetic and geno...

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