Structural Phylogenomics Reveals Gradual Evolutionary Replacement of Abiotic Chemistries by Protein Enzymes in Purine Metabolism

Abstract

The origin of metabolism has been linked to abiotic chemistries that existed in our planet at the beginning of life. While plausible chemical pathways have been proposed, including the synthesis of nucleobases, ribose and ribonucleotides, the cooption of these reactions by modern enzymes remains shrouded in mystery. Here we study the emergence of purine metabolism. The ages of protein domains derived from a census of fold family structure in hundreds of genomes were mapped onto enzymes in metabolic diagrams. We find that the origin of the nucleotide interconversion pathway benefited most parsimoniously from the prebiotic formation of adenine nucleosides. In turn, pathways of nucleotide biosynthesis, catabolism and salvage originated ∼300 million years later by concerted enzymatic recruitments and gradual replacement of abiotic chemistries. Remarkably, this process led to the emergence of the fully enzymatic biosynthetic pathway ∼3 billion years ago, concurrently with the appearance of a functional ribosome. The simultaneous appearance of purine biosynthesis and the ribosome probably fulfilled the expanding matter-energy and processing needs of genomic information.

Global Patterns of Protein Domain Gain and Loss in Superkingdoms

“…This lineage already produced superkingdoms Archaea and Bacteria by genomic streamlining, which was likely triggered by a host of selective pressures, including the escape from viruses and phagotrophs, the need to adapt to extreme environments (Archaea), and the benefits of rapid growth (Bacteria) [70]. The early rise of diversified Bacteria thus supports the existence of alpha-proteobacterial ancestors of mitochondria before the appearance of diversified eukaryotes 1.6 Gy ago ( nd  = 0.55), as indicated by microfossil evidence and the molecular clock [51], [52]. The fact that the first mitochondrial-specific FFs appeared at that time (Table 3) boosts the idea of the joint rise of Eukarya and eukaryotic organelles.…”

Structural Phylogenomics Retrodicts the Origin of the Genetic Code and Uncovers the Evolutionary Impact of Protein Flexibility

“…Protein-RNA coevolutionary interactions probably fixed specificities that were originally established by the ancient operational code, enabling genetic code expansions by structural recruitments and mutational change (Figure 3B). This late development coincided with the origin of ribosomal proteins at nd FF  = 0.114 and the inception of the ribosomal peptidyl transferase center (PTC) responsible for modern protein synthesis and the establishment of a fully functional ribosomal machine ∼2.8–3.1 Gy ago [23], together with pathways of amino acid [14] and purine nucleotide biosynthesis [56]. This suggests that tRNA encoding, ribosomal functionality, and modern metabolic pathways for amino acids and nucleotides developed concurrently, supporting the co-evolution theory of the genetic code [57].…”

Piecemeal Buildup of the Genetic Code, Ribosomes, and Genomes from Primordial tRNA Building Blocks

“…The functions of these FFs are linked to the start of modern metabolic networks, providing hydrolase and transferase functions needed for nucleotide interconversion, storage and phosphate transfer-mediated recycling of chemical energy, and terminal production of beneficial cofactors (e.g., [40]). The early evolution of metabolism in association with nucleotide cofactors culminated with the appearance of the first enzymes of the biosynthetic pathways of nucleotide metabolism 3.5 Gy-ago and the completion of a functional biosynthetic pathway ~3 Gy-ago, which coincides with the rise of a functional ribosome [41]. These coordinated developments suggest the coevolutionary need of a steady supply of nucleotide precursors internal to the cell for the synthesis of large RNA molecules, large enough to store genomic information and fulfill the ribosomal role of processive biosynthesis.…”