Figure 1. displays the Nrf2 phylogenetic tree relative to atmospheric oxygen levels during the latter period of Earth’s history.

The chart presents the traditional “5-stage model” of oxygen evolution constructed from compiled data¹,⁸,⁹,¹⁰,¹¹,¹²,¹³,¹⁴,¹⁵, with the trend line representing a “best guess” model; Stage 1 represents a period when the atmosphere and oceans were largely anoxic; Stage 2 commences the ‘Great Oxygenation Event’; Stage 3 is the period during which atmospheric oxygen levels remained low due to continued absorption by the oceans and oxidative weathering of the terrestrial crust; Stage 4 is the period after saturation of global oxygen buffers, during which oxygen levels rise towards present (Stage 5) atmospheric levels (PAL). The Earth timeline and major geological periods⁴³ are compiled and coloured by age. Eukarya and cyanobacteria appearances are noted according to first confirmed fossil evidence¹⁷. Proposed time frames are shown for major Nrf2 divergence and recruitment events. Taxa known or predicted to contain the Keap1-Nrf2 signalling pathway are denoted by the vertical green bar, while taxa containing Nrf2 only (without Keap1) are denoted in blue. Invertebrates with an experimentally validated Nrf2 system are marked with a star (*). Evolutionary pressure increases towards more recently evolved phyla as schematically shown by an increasing orange hue in the selective pressure bar (decrease in dN-dS test statistic and decrease in p-value for null hypothesis of neutral evolution).