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

TLDR

Metabolism is thought to have originated from early abiotic chemistries, yet how these reactions were incorporated into modern enzymes remains unclear. This study investigates how purine metabolism emerged. By mapping the evolutionary ages of protein domain folds across hundreds of genomes onto metabolic enzymes, the authors reconstruct the timing of enzymatic recruitment. They find that prebiotic adenine nucleosides first enabled nucleotide interconversion, and that subsequent enzymatic recruitment over the next ~300 million years replaced abiotic steps, culminating in a fully enzymatic purine biosynthetic pathway about 3 billion years ago alongside the ribosome, thereby meeting the growing informational demands of genomes.

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.