The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture

doi:10.1073/pnas.0701214104

The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture

^†Departments of Crop Sciences and
^§Cell and Developmental Biology, University of Illinois at Urbana–Champaign, Urbana, IL 61801

Edited by Philip P. Green, University of Washington School of Medicine, Seattle, WA, and approved April 23, 2007 (received for review February 8, 2007)

Abstract

Metabolism represents a complex collection of enzymatic reactions and transport processes that convert metabolites into molecules capable of supporting cellular life. Here we explore the origins and evolution of modern metabolism. Using phylogenomic information linked to the structure of metabolic enzymes, we sort out recruitment processes and discover that most enzymatic activities were associated with the nine most ancient and widely distributed protein fold architectures. An analysis of newly discovered functions showed enzymatic diversification occurred early, during the onset of the modern protein world. Most importantly, phylogenetic reconstruction exercises and other evidence suggest strongly that metabolism originated in enzymes with the P-loop hydrolase fold in nucleotide metabolism, probably in pathways linked to the purine metabolic subnetwork. Consequently, the first enzymatic takeover of an ancient biochemistry or prebiotic chemistry was related to the synthesis of nucleotides for the RNA world.

Footnotes

^‡To whom correspondence should be addressed. E-mail: gca{at}uiuc.edu
Author contributions: G.C.-A. and J.E.M. designed research; G.C.-A. and H.S.K. performed research; G.C.-A. analyzed data; and G.C.-A. wrote the paper and secured funding.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0701214104/DC1.
Abbreviations:

EC,

Enzyme Commission;

KEGG,

Kyoto Encyclopedia of Genes and Genomes;

MANET,

molecular ancestry network;

RCC,

reduced cladistic consensus;

SCOP,

Structural Classification of Proteins;

BS,

bootstrap support;

CI,

consistency index;

PTP,

permutation tail probability.