Whether evolution can go back to an ancestral structure by reversing the selection pressure on function has long fascinated biologists. Here, the evolution of hormone specificity in the vertebrate glucocorticoid receptor is used as a case-study to investigate this issue; the mutations that optimized the new specificity of the glucocorticoid receptor are found to have destabilized elements of the protein structure that were required to support the ancestral conformation.
- Jamie T. Bridgham
- Eric A. Ortlund
- Joseph W. Thornton