Functional Evolution of Proteins

+ See all authors and affiliations

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.

Related Content

Navigate This Article