The Molecular Ancestry Network (MANET) database project traces evolution of protein architecture onto biomolecular networks. We have constucted a metabolic MANET database with the objective of investigating the ancestry of individual metabolic enzymes and the evolution of metabolism with bioinformatic, phylogenetic, and statistical methods. MANET currently links information in the Structural Classification of Proteins (SCOP) database, the metabolic pathways database of the Kyoto Encyclopedia of Genes and Genomes (KEGG), and phylogenetic reconstructions describing the evolution of protein fold architecture at a universal level. MANET literally "paints" the ancestries of enzymes derived from rooted phylogenetic trees directly onto metabolic subnetwork representation. It also provides numerous functionalities that enable searching specific protein folds with defined ancestry values, displaying the distribution of enzymes that are painted, and exploring quantitative details describing individual protein folds. Our database traces the evolution of enzymes that belong to every one of over one hundred metabolic pathways. This permits the study of global and local metabolic network architectures, and the extraction of evolutionary patterns at global and local levels. A preliminary statistical analysis of the data shows a patchy distribution of ancestry values assigned to protein folds in each subnetwork. This suggests that evolution of metabolism occurred globally by wide spread recruitment of enzymes. To our knowledge, MANET represents the first attempt to map evolutionary relationships directly onto biological networks.

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