Figure 4.

Reconstructed evolutionary history of the PCAD–Memo domain and relation to other lineages in the PNP-peptide hydrolase fold. Major evolutionary transitions are marked by vertical black lines, distinguishing relative temporal eras. Individual lineages, labeled to the right, are traced to their maximal inferred evolutionary depth by horizontal lines, which are colored by extant phyletic distributions. Broken horizontal lines indicate a lineage cannot be traced beyond a certain point. Yellow circles denote loss of conserved residues needed for the enzymatic activities observed across fold lineages. Red lines mark key structural and/or functional transitions, further illustrated by chemical reaction diagrams in gray boxes. Recurrence of genomic AMMECR1 association across the PCAD–Memo domain are denoted at the right of the lineage names.