Evolutionary oxidation of proteins in Earth’s history

Abstract Evidence for Earth’s oxygenation during the Great Oxidation Event (GOE) and Neoproterozoic Oxidation Event (NOE) comes primarily from the geological record. We report rising oxidation state of carbon (Zc) in proteins over billion-year timescales, a consistent trend recovered from diverse genomic datasets. Combining statistical and thermodynamic modeling, we link this trend to environmental drivers including Earth’s progressive oxygenation and secular cooling. The oxidation trend appears in the amino acid composition of modern genomes from methanogens and sulfur-cycling organisms, phylostratigraphic gene age groups in eukaryotes, and reconstructed ancestral sequences for Rubisco, nitrogenase, thioredoxin, and 3-isopropylmalate dehydrogenase (IPMDH). Major Zc steps broadly overlap the GOE but do not exactly coincide with it; uncertainties in phylogenetic age and limited spatial associations complicate direct comparison with geochemical proxies. Gene age groups in unicellular, but not multicellular, eukaryotes show a second rise of protein Zc around the NOE. These widespread genomic signatures of protein oxidation are consistent with a thermodynamic hypothesis in which energy minimization directs protein sequence evolution across metabolic functions.