EVOLUTION OF THE ANDROGEN RECEPTOR - STRUCTURE-FUNCTION IMPLICATIONS

To shed light on the nature and evolution of structure-function relati ons in the androgen receptor (AR), we have undertaken a comparative an alysis of ail available AR and other steroid receptor sequences. We ha ve identified a group of amino acids that ''diagnose'' the clade of an drogen receptors-residues that are strictly conserved among the ARs bu t not shared with other receptors. We hypothesize that these amino aci ds, clustered in a few regions of the protein, confer upon the androge n receptor its unique functions, including recognition of specific DNA response elements and affinity for androgens, rather than other stero id hormones. The four domains of the AR display markedly different rat es of evolutionary divergence; conserved portions of the sequence, inc luding small stable stretches within otherwise divergent regions, may be essential to receptor function. Current data from experimental, cry stallographic, and clinical studies support these hypotheses, which ca n now be further tested in the laboratory. (C) 1998 John Wiley a Sons, Inc.