Phylogenetic analysis of metabolic pathways

The information provided by completely sequenced genomes can yield insights into the multi-level organization of organisms and their evolution. At the lowest level of molecular organization individual enzymes are formed, ofte n through assembly of multiple polypeptides. At a higher level, sets of enz ymes group into metabolic networks. Much has been learned about the relatio nship of species from phylogenetic trees comparing individual enzymes. In t his article we extend conventional phylogenetic analysis of individual enzy mes in different organisms to the organisms' metabolic networks. For this p urpose we suggest a method that combines sequence information with informat ion about the underlying reaction networks. A distance between pathways is defined as incorporating distances between substrates and distances between corresponding enzymes. The new analysis is applied to electron-transfer an d amino acid biosynthesis networks yielding a more comprehensive understand ing of similarities and differences between organisms.