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This Article Full Text Full Text (PDF) All Versions of this Article: 586/1/83    most recent jphysiol.2007.144709v2 jphysiol.2007.144709v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Koch, L. G. Articles by Britton, S. L. Search for Related Content PubMed PubMed Citation Articles by Koch, L. G. Articles by Britton, S. L. Related Collections Review articles Integrative

¹ Functional Genomics Laboratory, Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI 48109-2200, USA

The evolution of biological complexity beyond single-celled organisms was linked temporally with the development of an oxygen atmosphere. Functionally, this linkage can be attributed to oxygen ranking high in both abundance and electronegativity amongst the stable elements of the universe. That is, reduction of oxygen provides for close to the largest possible transfer of energy for each electron transfer reaction. This suggests the general hypothesis that the steep thermodynamic gradient of an oxygen environment was permissive for the development of multicellular complexity. A corollary of this hypothesis is that aerobic metabolism underwrites complex biological function mechanistically at all levels of organization. The strong contemporary functional association of aerobic metabolism with both physical capacity and health is presumably a product of the integral role of oxygen in our evolutionary history. Here we provide arguments from thermodynamics, evolution, metabolic network analysis, clinical observations and animal models that are in accord with the centrality of oxygen in biology.

(Received 17 September 2007; accepted after revision 8 October 2007; first published online 11 October 2007)
Corresponding author S. L. Britton: Functional Genomics Laboratory, 2220 Basic Science Research Building, Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI 48109-2200, USA. Email: brittons{at}umich.edu

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