Origin and evolution of the ligand-binding ability of nuclear receptors

Mol Cell Endocrinol. 2011 Mar 1;334(1-2):21-30. doi: 10.1016/j.mce.2010.10.017. Epub 2010 Nov 3.


The origin of the ligand-binding ability of nuclear receptors is still a matter of discussion. Current opposing models are the early evolution of an ancestral receptor that would bind a specific ligand with high affinity and the early evolution of an ancestral orphan that was a constitutive transcription factor. Here we review the arguments in favour or against these two hypotheses, and we discuss an alternative possibility that the ancestor was a ligand sensor, which would be able to explain the apparently contradictory data generated in previous models for the evolution of ligand binding in nuclear receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Evolution, Molecular*
  • Gene Expression
  • Gonadal Steroid Hormones / chemistry
  • Gonadal Steroid Hormones / metabolism
  • Humans
  • Ligands*
  • Models, Biological
  • Phylogeny
  • Protein Binding
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*
  • Steroids / chemistry
  • Steroids / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation


  • Gonadal Steroid Hormones
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Steroids
  • Transcription Factors