Fig. 7: Timeline of PRPS complex evolution in mammals and implications of distinct PRPS assembly states on cellular fitness.

A Chronological duplication events of a Class I PRPS encoding gene in indicated eukaryotes. Grey triangle traces the evolutionary trajectory leading to the emergence of mammalian PRPS homologs. Solid vertical lines within the triangle denote the origin of major lineages; dashed lines indicate significant duplication events giving rise to PRPS homologs, with notable functional innovations occurring post-duplication. Class II PRPS, likely present in the LECA, is lost in craniates, followed by rapid expansion of Class I PRPS homologs in jawed vertebrates. Left square bracket indicates a gene duplication event; left round bracket indicates an extension at the N-terminus. Molecular clock-based evolutionary timeline (in millions of years before present, Ma) adapted from ref. ⁵². B Association of different PRPS complex configurations with cellular fitness in mammals (i) PRPS1 alone undergoes self-assembly to form homo-oligomers. (ii) PRPS1 and AP1 cannot interact directly and form separate homo-oligomers. (iii) PRPS2 binds PRPS1 to form a dimer and disrupts PRPS1 homotypic assemblies. (iv) AP2 preferentially binds with PRPS1 to form a trimer/tetramer to nucleate the complex. (v) AP1 preferentially binds with AP2 and PRPS2 to elongate the PRPS complex via its N-terminus. (vi) The longer isoform of AP1 with flexible N-terminal extension likely caps the complex. The weight of the connectors between the circles representing proteins reflects the predicted strength of protein-protein interactions; heavier lines indicate stronger predicted interactions.