Christian Forst and Klaus Schulten.
Evolution of metabolisms: A new method for the comparison of
metabolic pathways using genomics information.
Journal of Computational Biology, 6:343-360, 1999.
FORS99B
The abundance of information provided by completely sequenced genomes defines a starting point for new insights in the multi-level organization of organisms and their evolution. At the lowest level enzymes and other protein complexes are formed by aggregating multiple polypeptides. At a higher level enzymes group conceptually into metabolic pathways as part of a dynamic information processing system, substrates are processed by enzymes yielding other substrates. A method based on a combination of sequence information with graph-topology of the underlying pathway is presented. With this approach pathways of different organisms are related to each other by phylogenetic analysis, extending conventioal phylogenetic analysis of individual enzymes. The new method is applied to pathways related to electron transfer and to the Krebs citric acid cycle. Beside a more comprehensive understanding of similarities and differences between organisms, this method indicates different evolutionary rates between substrates and enzymes.
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