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

Kelsey Caetano-Anollés,Gustavo Caetano-Anollés,Christos A Ouzounis

doi:10.1371/journal.pone.0059300

Kelsey Caetano-Anollés, Gustavo Caetano-Anollés + Show 1 more

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https://doi.org/10.1371/journal.pone.0059300

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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.

Highlights

While the origin of life remains mysterious, the principle of continuity dictates that simple chemistries must precede complex biochemistry
Tracing the age of protein domains in enzymes of purine metabolism at fold family level reveals the emergence of central purine metabolic pathways
In STRUCTURAL CLASSIFICATION OF PROTEINS (SCOP), domains that are evolutionarily closely related at the sequence level are clustered into fold families (FFs)

Summary

Introduction

While the origin of life remains mysterious, the principle of continuity dictates that simple chemistries must precede complex biochemistry. Cellular metabolism is driven by a complex collection of enzymes, most made solely of proteins and few involving nucleic acids (e.g., the RNase P complex) [1] These enzymes are responsible for the catalysis of metabolitetransforming chemical reactions and for metabolite transport in cellular systems. We put forth the hypothesis that enzyme recruitment in primordial cells benefitted from external prebiotic chemistries, which provided abundant raw materials and simplified the challenges of building efficient cellular metabolic systems from scratch. We test this hypothesis by asking if enzymatic recruitment history inferred from phylogenomic reconstruction is compatible with current understanding of prebiotic chemistry

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