Functional prediction: Identification of protein orthologs and paralogs

Orthologs typically retain the same function in the course of evolution. Us ing beta -decarboxylating dehydrogenase family as a model. we demonstrate t hat orthologs can be confidently identified The strategy is based on our re cent findings that substitutions of only a few amino acid residues in these enzymes are sufficient to exchange substrate and coenzyme specificities. H ence, the few major specificity determinants can serve as reliable markers for determining orthologous or paralogous relationships. The power of this approach has been demonstrated by correcting similarity-based functional mi sassignment and discovering new genes and related pathways, and should be b roadly applicable to other enzyme families.