Comparative genomics of nucleotide metabolism: a tour to the past of the three cellular domains of life

Background: Nucleotide metabolism is central to all biological systems, due to their essential role in genetic information and energy transfer, which in turn suggests its possible presence in the last common ancestor (LCA) of Bacteria, Archaea and Eukarya. In this context, elucidation of the contribution of the origin and diversification of de novo and salvage pathways of nucleotide metabolism will allow us to understand the links between the enzymatic steps associated with the LCA and the emergence of the first metabolic pathways. Results: In this work, the taxonomical distribution of the enzymes associated with nucleotide metabolism was evaluated in 1,606 complete genomes. 151 sequence profiles associated with 120 enzymatic reactions were used. The evaluation was based on profile comparisons, using RPS-Blast. Organisms were clustered based on their taxonomical classifications, in order to obtain a normalized measure of the taxonomical distribution of enzymes according to the average of presence/absence of enzymes per genus, which in turn was used for the second step, to calculate the average presence/absence of enzymes per Clade. Conclusion: From these analyses, it was suggested that divergence at the enzymatic level correlates with environmental changes and related modifications of the cell wall and membranes that took place during cell evolution. Specifically, the divergence of the 5-(carboxyamino) imidazole ribonucleotide mutase to phosphoribosylaminoimidazole carboxylase could be related to the emergence of multicellularity in eukaryotic cells. In addition, segments of salvage and de novo pathways were probably complementary in the LCA to the synthesis of purines and pyrimidines. We also suggest that a large portion of the pathway to inosine 5'-monophosphate (IMP) in purines could have been involved in thiamine synthesis or its derivatives in early stages of cellular evolution, correlating with the fact that these molecules may have played an active role in the protein-RNA world. The analysis presented here provides general observations concerning the adaptation of the enzymatic steps in the early stages of the emergence of life and the LCA.