Abstract

In mammals, circadian periodicity has been described for gene expression in the hypothalamus and multiple peripheral tissues. It is accepted that 10%–15% of all genes oscillate in a daily rhythm, regulated by an intrinsic molecular clock. Statistical analyses of periodicity are limited by the small size of datasets and high levels of stochastic noise. Here, we propose a new approach applying digital signal processing algorithms separately to each group of genes oscillating in the same phase. Combined with the statistical tests for periodicity, this method identifies circadian baseline oscillation in almost 100% of all expressed genes. Consequently, circadian oscillation in gene expression should be evaluated in any study related to biological pathways. Changes in gene expression caused by mutations or regulation of environmental factors (such as photic stimuli or feeding) should be considered in the context of changes in the amplitude and phase of genetic oscillations.

Highlights

  • Periodic patterns are widespread in the behavior, physiology, and gene expression of almost all organisms from cyanobacteria to humans

  • Many researchers have demonstrated that the analysis of circadian rhythms is important for a complete understanding of both physiology and pathology in mammalian and other species [3,4]

  • A series of experimental and computational studies of gene expression in various murine tissues has led us to a different conclusion

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Summary

Introduction

Periodic patterns are widespread in the behavior, physiology, and gene expression of almost all organisms from cyanobacteria to humans. The most prevalent oscillating pattern is circadian, or approximately daily rhythm. It is commonly accepted that up to 15% of all mammalian genes follow this rhythm entrained by photic stimuli resulting from the alternating light and dark periods of the day. The central circadian clock is located in the suprachiasmic nucleus in the brain [2], but active molecular clocks, presumably synchronized by suprachiasmic nucleus–mediated activity, have been reported in peripheral tissues. Many researchers have demonstrated that the analysis of circadian rhythms is important for a complete understanding of both physiology and pathology in mammalian and other species [3,4]. Our recent findings demonstrate that the prominence and impact of oscillatory processes in living tissues may still be underestimated

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