Evolution of metabolisms: A new method for the comparison of metabolic pathways using genomics information

The abundance of information provided by completely sequenced genomes defin es a starting point for new insights in the multilevel organization of orga nisms and their evolution, At the lowest level enzymes and other protein co mplexes are formed by aggregating multiple polypeptides. At a higher level enzymes group conceptually into metabolic pathways as part of a dynamic inf ormation-processing system, and substrates are processed by enzymes yieldin g other substrates. A method based on a combination of sequence information with graph topology of the underlying pathway is presented. With this appr oach pathways of different organisms ape related to each other by phylogene tic analysis, extending conventional phylogenetic analysis of individual en zymes. The new method is applied to pathways related to electron transfer a nd to the Krebs citric acid cycle. In addition to providing a more comprehe nsive understanding of similarities and differences between organisms, this method indicates different evolutionary rates between substrates and enzym es.