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The conservation and evolutionary modularity of metabolism

José M Peregrín-Alvarez12*, Chris Sanford13 and John Parkinson134*

Author Affiliations

1 Program in Molecular Structure and Function, Hospital for Sick Children, College Street, Toronto, ON, M5G 1L7, Canada

2 Department of Molecular Biology and Biochemistry, University of Malaga, Avda. Cevantes, 29071 Malaga, Spain

3 Department of Molecular Genetics, University of Toronto, King's College Circle, Toronto, ON, M5S 1A8, Canada

4 Department of Biochemistry, University of Toronto, Toronto, Kings' College Circle, ON, M5S 1A8, Canada

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Genome Biology 2009, 10:R63  doi:10.1186/gb-2009-10-6-r63

Published: 12 June 2009



Cellular metabolism is a fundamental biological system consisting of myriads of enzymatic reactions that together fulfill the basic requirements of life. The recent availability of vast amounts of sequence data from diverse sets of organisms provides an opportunity to systematically examine metabolism from a comparative perspective. Here we supplement existing genome and protein resources with partial genome datasets derived from 193 eukaryotes to present a comprehensive survey of the conservation of metabolism across 26 taxa representing the three domains of life.


In general, metabolic enzymes are highly conserved. However, organizing these enzymes within the context of functional pathways revealed a spectrum of conservation from those that are highly conserved (for example, carbohydrate, energy, amino acid and nucleotide metabolism enzymes) to those specific to individual taxa (for example, those involved in glycan metabolism and secondary metabolite pathways). Applying a novel co-conservation analysis, KEGG defined pathways did not generally display evolutionary coherence. Instead, such modularity appears restricted to smaller subsets of enzymes. Expanding analyses to a global metabolic network revealed a highly conserved, but nonetheless flexible, 'core' of enzymes largely involved in multiple reactions across different pathways. Enzymes and pathways associated with the periphery of this network were less well conserved and associated with taxon-specific innovations.


These findings point to an emerging picture in which a core of enzyme activities involving amino acid, energy, carbohydrate and lipid metabolism have evolved to provide the basic functions required for life. However, the precise complement of enzymes associated within this core for each species is flexible.