THE ROLE OF GENE DUPLICATION IN THE EVOLUTION OF PURINE NUCLEOTIDE SALVAGE PATHWAYS

Purine nucleotides are formed de novo by a widespread biochemical rout e that may be of monophyletic origin, or are synthesized from preforme d purine bases and nucleosides through different salvage pathways. Thr ee monophyletic sets of purine salvage enzymes, each of which catalyze s mechanistically similar reactions, can be identified: (a) adenine-, xanthine-, hypoxanthine- and guanine-phosphoribosyltransferases, which are all homologous among themselves, as well as to nucleoside phospho rylases; (b) adenine deaminase, adenosine deaminase, and adenosine mon ophophate deaminase; acid (c) guanine reductase and inosine monophosph ate dehydrogenase. These homologies support the idea that substrate sp ecificity is the outcome of gene duplication, and that the purine nucl eotide salvage pathways were assembled by a patchwork process that pro bably took place before the divergence of the three cell domains (Bact eria, Archaea, and Eucarya). Based on the ability of adenine PRTase to catalyze the condensation of PRPP with 4-aminoimidazole-5-carboxamide (AICA), a simpler scheme of purine nucleotide biosynthesis is present ed. This hypothetical route requires the prior evolution of PRPP biosy nthesis. Since it has been argued that PRPP, nucleosides, and nucleoti des are susceptible to hydrolysis, they are very unlikely prebiotic co mpounds. If this is the case, it implies that many purine salvage path ways appeared only after the evolution of phosphorylated sugar biosynt hetic pathways made ribosides available.