Oxygen, epigenetic signaling, and the evolution of early life

º Reversible methylation of DNA and lysine residues is essential for cellular differentiation. º Removal of methyl groups from lysine and DNA requires oxygen. º Multicellular animals appeared only after enrichment of atmospheric oxygen. º The oxygen demand in demethylation may explain the timing of the origin of multicellular animals. After approximately 3 billion years of unicellular life on Earth, multicellular animals appeared some 600 million years ago, followed by the rapid emergence of most animal phyla during the Cambrian radiation. This evolutionary jump was paralleled by an increase in atmospheric oxygen, which I propose allowed the generation of epigenetic signaling systems that are essential for cellular differentiation in animals. Epigenetic signaling is based on the reversible deposition of chemically stable marks in DNA and histone proteins, with methylation of cytosine and lysine residues, respectively, playing a central role. Recent evidence indicates that the removal of such methyl groups critically depends on oxygenases. Hence, reversible epigenetic systems could only appear after accumulation of oxygen in the atmosphere.