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Evolution of Hormone-Receptor Complexity by Molecular Exploitation
Jamie T. Bridgham,Sean M. Carroll,Joseph W. Thornton*
According to Darwinian theory, complexity evolves by a stepwiseprocess of elaboration and optimization under natural selection.Biological systems composed of tightly integrated parts seemto challenge this view, because it is not obvious how any element'sfunction can be selected for unless the partners with whichit interacts are already present. Here we demonstrate how anintegrated molecular system—the specific functional interactionbetween the steroid hormone aldosterone and its partner themineralocorticoid receptor—evolved by a stepwise Darwinianprocess. Using ancestral gene resurrection, we show that, longbefore the hormone evolved, the receptor's affinity for aldosteronewas present as a structural by-product of its partnership withchemically similar, more ancient ligands. Introducing two aminoacid changes into the ancestral sequence recapitulates the evolutionof present-day receptor specificity. Our results indicate thattight interactions can evolve by molecular exploitation—recruitmentof an older molecule, previously constrained for a differentrole, into a new functional complex.
Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, OR 97403, USA.
* To whom correspondence should be addressed. E-mail: joet{at}uoregon.edu
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Protein Eng. Des. Sel.
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