Molecular differences in the HIF-like structures between the Porifera, Placozoa, Cnidaria, Bilateria and within Bilateria 43 , 53 , with phylogeny of animal lineages based on ref. 96 , with approximate divergence between lineages based 97 and ref. 71 ). A maximum diversity of components to the OSM is depicted per lineage in a simplified phylogeny 97 (to Lophotrochozoa (L), Ecdysozoa (E), Ambulacraria (A) and Chordata (C) for Bilateria), based on sequences in ref. 53 and ref. 43 (see SI text and Supplementary Table 4 for details). Proteins were not drawn in scale and the position of the components are approximate. The HIF-like bHLH (grey) and PAS (blue) is common to all, while the P564 (green triangle) appear from Cnidaria and Placozoa and CTAD (in Cnidaria (pale red when uncertain, see Supplementary Table 4 ) and Bilateria (red). Within Bilateria, multiple combinations of P564, CTAD plus P402 (purple triangle), NTAD (yellow, pale yellow when uncertain) and FIH (black triangle and grey when uncertain) are present. *asparagine 803 which is the FIH interaction site.** depicts human reference with also HIF-2α.
