Figure 3. Timeline describing the evolution of FF domain structures and the evolution of main pathways of purine metabolism.

The timeline was derived directly from the tree of FFs reconstructed from free-living organisms. Ages are given as node distances (nd_FF) and geological time (Gy). Time flows from top to bottom. The three evolutionary epochs of the protein world defined by Wang et al. [8], “architectural diversification” (epoch 1), “superkingdom specification” (epoch 2), and “organismal diversification” (epoch 3) are overlapped to the timeline (colored with different shades). Landmark discoveries [18], [19] are identified with circles along the timeline. The inset below describes the evolution of the 54 most ancient FFs. Stars represent the fulfillment of a full repertoire of enzymes in a central pathway.