Christian V. Forst and Klaus Schulten.
Evolution of metabolisms: A new method for the comparison of
metabolic pathways.
In Sorin Istrail, Pavel Pevzner, and Michael Waterman, editors,
Proceedings of the Third Annual International Conference on Computational
Molecular Biology, pp. 174-180, Lyon, France, 1999. ACM Press, New York.
FORS99
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 new method based on a combination of sequence information with graph-topology of the underlying pathway is presented. By this approach pathways of different organisms are related to each other by phylogenetic analysis: Metabolic pathways in organisms are assigned by the presence of genes with corresponding functions. A global distance between pathways is defined by using individual distances between sequences of the same functional role. Gap-penalties are introduced for existing pathways with missing functional roles. As an example the method is applied to pathways related to the utilization of ferredoxin as redox-agent. First results report a high versatility and controversial phylogenies. Pathway which evolve early in evolution are present in organisms of all three domains (Archaea, Bacteria and Eucarya). Functional roles which are utilized in these very pathways are common in many pathways of the cell. Pathways which are only present in organisms of a single (or at maximum two) domains often perform "pathologic" tasks with rare and specialized functional roles. As example serves NADPH - Hg Electron transport with mercury(II) reductase reaction as enzyme. Beside a more comprehensive understanding of similarities and differences between organisms, this method already indicates different evolutionary rates between substrates and enzymes. It is also capable to hint towards variation and specialization of pathways in the sense of an evolution of metabolisms.
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Electron transport with mercury(II) reductase reaction as enzyme. Beside a more comprehensive understanding of similarities and differences between organisms, this method already indicates different evolutionary rates between substrates and enzymes. It is also capable to hint towards variation and specialization of pathways in the sense of an evolution of metabolisms. 
