Christian Forst and Klaus Schulten.
Phylogenetic analysis of metabolic pathways.
Journal of Molecular Evolution, 52:471-489, 2001.
FORS2001
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, often through assembly of multiple polypeptides, and at a higher level, sets of enzymes group into metabolic networks. Much has been learned about the relationship of species from phylogenetic trees comparing individual enzymes. In this article we extend conventional phylogenetic analysis of individual enzymes in different organisms to the organisms' metabolic networks. For this purpose we suggest a method that combines sequence information with information about the underlying reaction networks. A distance between pathways is defined that incorporates distances between substrates and distances between corresponding enzymes. The new analysis is applied to electron-transfer and amino acid biosynthesis networks yielding a more comprehensive understanding of similarities and differences between organisms.
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