Evolution of the androgen receptor: Structure-function implications. Bioessays

To shed light on the nature and evolution of structure–function relations in the androgen receptor (AR), we have undertaken a comparative analysis of all available AR and other steroid receptor sequences. We have identified a group of amino acids that ‘‘diagnose’ ’ the clade of androgen receptors—residues that are strictly conserved among the ARs but not shared with other receptors. We hypothesize that these amino acids, clustered in a few regions of the protein, confer upon the androgen receptor its unique functions, including recognition of specific DNA response elements and affinity for androgens, rather than other steroid hormones. The four domains of the AR display markedly different rates of evolutionary divergence; conserved portions of the sequence, including small stable stretches within otherwise divergent regions, may be essential to receptor function. Current data from experimental, crystallographic, and clinical studies support these hypotheses, which can now be further tested in the laboratory