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Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6803-8.

Ligand binding was acquired during evolution of nuclear receptors.

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  • 1Institut National de la Santé et de la Recherche Médicale U167 Relations Hôte-Parasite et Stratégies Vaccinales, Institut Pasteur de Lille, 1 rue Calmette, 59019, Lille Cedex, France.


The nuclear receptor (NR) superfamily comprises, in addition to ligand-activated transcription factors, members for which no ligand has been identified to date. We demonstrate that orphan receptors are randomly distributed in the evolutionary tree and that there is no relationship between the position of a given liganded receptor in the tree and the chemical nature of its ligand. NRs are specific to metazoans, as revealed by a screen of NR-related sequences in early- and non-metazoan organisms. The analysis of the NR gene duplication pattern during the evolution of metazoans shows that the present NR diversity arose from two waves of gene duplications. Strikingly, our results suggest that the ancestral NR was an orphan receptor that acquired ligand-binding ability during subsequent evolution.

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