Functional Evolution of Proteins

Science  14 Sep 2007:
Vol. 317, Issue 5844, pp. 1465h
DOI: 10.1126/science.317.5844.1465h

The direct identification of protein evolution mechanisms requires comparing proteins through evolutionary time. The sequence of the 450-million-year-old ancestor of vertebrate mineralocorticoid (MR) and glucocorticoid (GR) was previously determined by phylogenetic analysis, and the ancestor was shown to have MR-like hormone specificity. Ortlund et al. (p. 1544, published online 16 August; see the 17 August news story by Service) used structural, functional, and phylogenetic analysis to determine how specific mutations resulted in a change from MR-like to GR hormone specificity. They find evidence for epistatic interactions where a substitution changed the conformation at another site. Substitutions that had no immediate functional effect, but affected stability to allow subsequent functional switching mutations, played an important role in GR evolution.

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