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Protein Folds Research Offers Insight into Metabolic Evolution

of Genes and Genomes, and the Structural Classification of Proteins database.

They combined these two data sets with phylogenetic reconstructions, or family trees, of protein fold architectures in metabolism. They created a new database, called the Molecular Ancestry Network (MANET) which connects these data sources into a new global network diagram of metabolic pathways.

The researchers added colour, representing evolutionary age, to their diagrams of metabolic networks (for an example, see the purine metabolism network in MANET). The result is a multicolored mosaic of protein fold evolution. The mosaic shows that modern metabolic networks and even individual enzymes are composed of both very ancient and much more recent protein architectures.

This mosaic is telling you that the new enzymes and old enzymes are together performing side by side, Caetano-Anolls said. In some cases in the same protein you have old domains and new domains working together.

This finding supports the hypothesis that protein architectures that execute one function are often recruited to complete new tasks.

The new, global family tree of protein architecture also exposed that many metabolic protein folds are quite ancient: These architectures were found to be quite common in all the species of bacteria, animals, plants, fungi, protists and archaea the researchers analyzed.

Of 776 metabolic protein folds surveyed, 16 were found to be universal, and nine of those occurred in the earliest branches of the newly constructed tree.

These nine ancient folds represent architectures of fundamental importance undisputedly encoded in a genetic core that can be traced back to the universal ancestor of the three super kingdoms of life, the authors wrote.

The analysis also found that the most ancient metabolic protein folds are vital to RNA metabolism, particularly the interconversion of the puri
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