Ligand binding and nuclear receptor evolution

Bioessays. 2000 Aug;22(8):717-27. doi: 10.1002/1521-1878(200008)22:8<717::AID-BIES5>3.0.CO;2-I.


Nuclear receptors form a superfamily of ligand-activated transcription factors that regulate various physiological functions, from development to homeostasis, in metazoans. The superfamily contains not only receptors for known ligands but also a large number of so-called orphan receptors for which ligands do not exist or have not been identified. The evolution of ligand-binding capacity of nuclear receptors may involve either secondary loss in orphan receptors, or evolutionary acquisition of ligand-binding capacity in liganded receptors. In this review, we present arguments from phylogenetic, functional and structural studies that support the hypothesis that there have been several independent gains of ligand-binding ability of nuclear receptors during metazoan evolution.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Evolution
  • Humans
  • Ligands
  • Models, Biological
  • Phylogeny
  • Receptors, Cytoplasmic and Nuclear / classification
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*


  • Ligands
  • Receptors, Cytoplasmic and Nuclear