Ligand binding and nuclear receptor evolution

Nuclear receptors form a superfamily of ligand-activated transcription fact ors that regulate various physiological functions, from development to home ostasis, in metazoans. The superfamily contains not only receptors for know n ligands but also a large number of so-called orphan receptors for which l igands do not exist or have not been identified. The evolution of ligand-bi nding capacity of nuclear receptors may involve either secondary loss in or phan receptors, or evolutionary acquisition of ligand-binding capacity in l iganded receptors. In this review, we present arguments from phylogenetic, functional and structural studies that support the hypothesis that there ha ve been several independent gains of ligand-binding ability of nuclear rece ptors during metazoan evolution. (C) 2000 John Wiley & Sons, Inc.