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Title:
Evolution of Hormone-Receptor Complexity by Molecular Exploitation
Authors:
Bridgham, Jamie T.; Carroll, Sean M.; Thornton, Joseph W.
Publication:
Science, Volume 312, Issue 5770, pp. 97-101 (2006). (Sci Homepage)
Publication Date:
04/2006
Category:
EVOLUTION
Origin:
SCIENCE
Abstract Copyright:
(c) 2006: Science
DOI:
10.1126/science.1123348
Bibliographic Code:
2006Sci...312...97B

Abstract

According to Darwinian theory, complexity evolves by a stepwise process of elaboration and optimization under natural selection. Biological systems composed of tightly integrated parts seem to challenge this view, because it is not obvious how any element's function can be selected for unless the partners with which it interacts are already present. Here we demonstrate how an integrated molecular system-the specific functional interaction between the steroid hormone aldosterone and its partner the mineralocorticoid receptor-evolved by a stepwise Darwinian process. Using ancestral gene resurrection, we show that, long before the hormone evolved, the receptor's affinity for aldosterone was present as a structural by-product of its partnership with chemically similar, more ancient ligands. Introducing two amino acid changes into the ancestral sequence recapitulates the evolution of present-day receptor specificity. Our results indicate that tight interactions can evolve by molecular exploitation-recruitment of an older molecule, previously constrained for a different role, into a new functional complex.
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