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

Christian V. Forst, Klaus Schulten

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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-Hg2+ 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.

Original languageEnglish
Title of host publicationProceedings of the Annual International Conference on Computational Molecular Biology, RECOMB
Place of PublicationNew York, NY, United States
PublisherACM
Pages174-181
Number of pages8
StatePublished - Jan 1 1999
EventProceedings of the 1999 3rd Annual International Conference on Computational Molecular Biology, RECOMB '99 - Lyon
Duration: Apr 11 1999Apr 14 1999

Other

OtherProceedings of the 1999 3rd Annual International Conference on Computational Molecular Biology, RECOMB '99
CityLyon
Period4/11/994/14/99

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Computer Science(all)

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  • Cite this

    Forst, C. V., & Schulten, K. (1999). Evolution of metabolisms: A new method for the comparison of metabolic pathways. In Proceedings of the Annual International Conference on Computational Molecular Biology, RECOMB (pp. 174-181). ACM.