Cellular life emerged ∼3.7 billion years ago. With scant exception, terrestrial organisms have evolved under predictable daily cycles owing to the Earth’s rotation. The advantage conferred on organisms that anticipate such environmental cycles has driven the evolution of endogenous circadian rhythms that tune internal physiology to external conditions. The molecular phylogeny of mechanisms driving these rhythms has been difficult to dissect because identified clock genes and proteins are not conserved across the domains of life: Bacteria, Archaea and Eukaryota. Here we show that oxidation–reduction cycles of peroxiredoxin proteins constitute a universal marker for circadian rhythms in all domains of life, by characterizing their oscillations in a variety of model organisms. Furthermore, we explore the interconnectivity between these metabolic cycles and transcription–translation feedback loops of the clockwork in each system. Our results suggest an intimate co-evolution of cellular timekeeping with redox homeostatic mechanisms after the Great Oxidation Event ∼2.5 billion years ago. Daily oxidation–reduction cycles of peroxiredoxin proteins are shown to be conserved in all domains of life, including Bacteria, Archaea and Eukaryota. Most living organisms possess an endogenous circadian clock that ties their metabolism to a 24-hour day–night cycle. 'Clock genes' have been studied in many organisms and their variety has encouraged the view that each clock evolved independently. But there is a unifying factor: a non-transcriptionally based form of circadian oscillation, involving the oxidation–reduction cycles of peroxiredoxin proteins, has been identified in human red blood cells and algae. This study demonstrates that these redox cycles are conserved in all domains of life, including Bacteria, Archaea and Eukaryota, pointing to the possibility that this type of cellular timekeeping has co-evolved with redox homeostatic mechanisms across organisms for billions of years. The link may go back 2.5 billion years, to the Great Oxidation Event that consigned anaerobic metabolism to the margins of evolutionary history.

Peroxiredoxins are conserved markers of circadian rhythms