Exploring Convergent Evolution to Provide a Foundation for Protein Engineering

摘要

Pathway holes correspond to steps in a pathway for which a homologue of known enzymes cannot be identified even though other enzymes in the pathway are present. Pathway holes can occur when an organism has independently evolved an enzyme to provide a catalytic function supplied by a structurally and possibly mechanistically different enzyme in other organisms. We have approached the identification of convergently evolved enzymes that fill pathway holes using both bioinformatic and experimental approaches. We have developed algorithms for generating divergent sets of protein sequences (Divergent Set) and for clustering proteins according to the patterns of motifs found by MEME (Motif Cluster). These algorithms can be used to search the database for sequences that are annotated with the same function and to cluster the sequences into families, thus revealing groups of sequences that show little relationship to each other and may therefore have evolved independently. We have identified a 'missing enzyme' in Thermoplasma volcanium and are tracking down another enzyme that is 'missing' in most Archaea. We have also developed the framework and ontology for a database of convergently evolved enzymes and have begun to populate the database.