Evolution of modern metabolism

Gustavo Caetano-Anollés, Hee Shin Kim and Jay E. Mittenthal Departments of Crop Sciences and Department of Cell and Developmental Biology

Protein domains are evolutionary units of structure and function in globular proteins. Domains fold into three-dimensional structures that can be classified in a hierarchy of levels – folds, fold superfamilies, and families. Using a genomic census of protein architecture, we recently generated phylogenies that describe the evolution of the protein world at these levels. We painted the relative ages (ancestries) of enzymes derived from these genomic-based phylogenies (phylogenomic trees of folds) directly onto over a hundred metabolic subnetworks, linked metabolic enzymes to folds with hidden Markov models (hmms) in almost a million genomic sequences, and used this information to build the Molecular Ancestry Network (MANET) database (http://manet.uiuc.edu). Evolutionarily painted subnetworks revealed a patchy distribution of ancestries in metabolism (a literal evolutionary mosaic) that suggests widespread recruitment of enzymes from one context to another. Using phylogenetic methods, we sorted out recruitment processes and identified an origin for modern metabolism. We also revealed patterns that suggest a dominant role of carbohydrate and amino acid metabolism in evolution of this complex biological network.