An epistatic ratchet constrains the direction of glucocorticoid receptor evolution

Jamie T. Bridgham, Eric A. Ortlund and Joseph W. Thornton ()
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Jamie T. Bridgham: Center for Ecology and Evolutionary Biology, and,
Eric A. Ortlund: Emory University School of Medicine, Atlanta, Georgia 30322, USA
Joseph W. Thornton: Center for Ecology and Evolutionary Biology, and,

Nature, 2009, vol. 461, issue 7263, 515-519

Abstract: Evolution has no reverse Whether evolution can go back to an ancestral structure just by reversing the selection pressure on function has been a long-standing issue, but one hard to address based on just the history of forms. Bridgham et al. have now physically reconstituted ancient versions of a regulatory protein (the glucocorticoid receptor) and dissected the structural constraints imposed on the evolution of their function (which hormone they bind) at atomic resolution. They find that amino acids that were essential in an ancestral protein become neutral in a more recent form, where they are then subject to erosion by genetic drift. This loss deprives natural selection of the necessary raw material with which to reverse the historical substitutions — they are no longer 'adaptive' as they were in the other direction. Evolutionarily speaking, there is no turning back.

Date: 2009
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DOI: 10.1038/nature08249

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