How hemoglobin evolves - a study of the relationship between physiology and evolution

13 October 2006

Ron Milo
Department of Systems Biology


The fitness of an organism to a changing environment is dependant to a large degree on its physiology. This suggests an interdependence between physiological plasticity and evolutionary adaptation. Many qualitative suggestions had been put forth throughout the years regarding this relationship. We set out to quantitatively analyze the changes taking part in these two different time scales using hemoglobin (Hb) as a model system. We compiled measurements of binding curves of oxygen to hemoglobin from the literature. The resulting database gives a phenotypic characterization of hemoglobin function for several dozen organisms and in different physiological conditions. We used a simple model that describes Hb function, the Monod-Wyman-Changeux (MWC) model, to effectively describe each binding curve using three independent parameters which describe the affinities (Kr, Kt) of the two conformations of Hb and an equilibrium constant (L0). Do all parameters change through evolution or are some parameters more conserved and others more variable? Are the parameters affected by different physiological conditions the same ones that change on evolutionary timescales? We find that there is a tendency for Kr to change in evolution much more than Kt, whereas under physiological conditions Kt changes much more than Kr. Therefore different parameters are tuned in these different regimes. This can be explained by suggesting that selection favors evolutionary changes that conserve physiological plasticity.

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