Journal of Molecular Evolution

, Volume 82, Issue 2–3, pp 146–161 | Cite as

Flux Control in Glycolysis Varies Across the Tree of Life

  • Alena Orlenko
  • Russell A. Hermansen
  • David A. Liberles
Original Article


Biochemical thought posits that rate-limiting steps (defined here as points of flux control) are strongly selected as points of pathway regulation and control and are thus expected to be evolutionarily conserved. Conversely, population genetic thought based upon the concepts of mutation-selection-drift balance at the pathway level might suggest variation in flux controlling steps over evolutionary time. Glycolysis, as one of the most conserved and best characterized pathways, was studied to evaluate its evolutionary conservation. The flux controlling step in glycolysis was found to vary over the tree of life. Further, phylogenetic analysis suggested at least 60 events of gene duplication and additional events of putative positive selection that might alter pathway kinetic properties. Together, these results suggest that even with presumed largely negative selection on pathway output on glycolysis, the co-evolutionary process under the hood is dynamic.


Glycolysis Metabolic pathway Evolutionary systems biology Protein co-evolution 



We thank Jan Kubelka, Ryan Gutenkunst, and Claudia Weber for helpful comments on this manuscript. This work was supported by NSF DBI- 0743374.

Supplementary material

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Supplementary material 1 (PDF 660 kb)
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Supplementary material 4 (PDF 3057 kb)
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Supplementary material 5 (DOCX 27 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Alena Orlenko
    • 1
    • 2
  • Russell A. Hermansen
    • 1
    • 2
  • David A. Liberles
    • 1
    • 2
  1. 1.Department of Biology and Center for Computational Genetics and GenomicsTemple UniversityPhiladelphiaUSA
  2. 2.Department of Molecular BiologyUniversity of WyomingLaramieUSA

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