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Ligand binding and nuclear receptor evolution.

H Escriva1, F Delaunay, V Laudet

  • 1Ecole Normale Supérieure de Lyon, Lyon, France.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|August 5, 2000
PubMed
Summary
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Nuclear receptors are key transcription factors. This review suggests multiple independent gains of ligand-binding ability occurred during animal evolution, rather than ligand loss.

Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Genomics

Background:

  • Nuclear receptors are crucial ligand-activated transcription factors regulating physiological processes in animals.
  • The nuclear receptor superfamily includes receptors with known ligands and numerous "orphan" receptors with unidentified ligands.
  • The evolutionary origin of ligand-binding capacity in nuclear receptors is debated, with hypotheses including secondary loss or acquisition of function.

Purpose of the Study:

  • To review evidence supporting the hypothesis of multiple independent acquisitions of ligand-binding ability in nuclear receptors during metazoan evolution.
  • To analyze phylogenetic, functional, and structural data to understand nuclear receptor evolution.
  • To explore the evolutionary trajectories of ligand-binding capacity within the nuclear receptor superfamily.

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Main Methods:

  • Phylogenetic analyses of nuclear receptor sequences.
  • Functional studies investigating receptor-ligand interactions.
  • Structural biology approaches to examine receptor-ligand binding domains.

Main Results:

  • Phylogenetic data indicate distinct evolutionary histories for different nuclear receptor clades.
  • Functional and structural evidence suggests convergent evolution of ligand-binding domains in several instances.
  • The pattern of receptor evolution is more consistent with acquisition of ligand-binding than widespread loss.

Conclusions:

  • The available evidence strongly supports the hypothesis that ligand-binding ability in nuclear receptors has been acquired independently multiple times during metazoan evolution.
  • This contrasts with the notion of widespread secondary loss of ligands in orphan receptors.
  • Understanding these evolutionary events provides insights into the diversification and functional adaptation of nuclear receptors.