The relationship between evolutionary and physiological variation in hemoglobin

Ron Milo, Jennifer H. Hou, Michael Springer, Michael P. Brenner, Marc W. Kirschner

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Physiological and evolutionary adaptations operate at very different time scales. Nevertheless, there are reasons to believe there should be a strong relationship between the two, as together they modify the phenotype. Physiological adaptations change phenotype by altering certain microscopic parameters; evolutionary adaptation can either alter genetically these same parameters or others to achieve distinct or similar ends. Although qualitative discussions of this relationship abound, there has been very little quantitative analysis. Here, we use the hemoglobin molecule as a model system to quantify the relationship between physiological and evolutionary adaptations. We compare measurements of oxygen saturation curves of 25 mammals with those of human hemoglobin under a wide range of physiological conditions. We fit the data sets to the Monod-Wyman-Changeux model to extract microscopic parameters. Our analysis demonstrates that physiological and evolutionary change act on different parameters. The main parameter that changes in the physiology of hemoglobin is relatively constant in evolution, whereas the main parameter that changes in the evolution of hemoglobin is relatively constant in physiology. This orthogonality suggests continued selection for physiological adaptability and hints at a role for this adaptability in evolutionary change.

Original languageEnglish
Pages (from-to)16998-17003
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
StatePublished - 23 Oct 2007
Externally publishedYes


  • Adaptability
  • Allosteric
  • Baldwin effect
  • Evolvability
  • Monod-Wyman-Changeux


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