Nuclear Receptor Genes: Evolution


Nuclear receptor superfamily members are metazoan innovations which are present in all living metazoan phyla. These genes, presumably originating from a common ancestor in an extinct phylum that predates the sponge (Porifera), has evolved, and is still evolving, to mediate nearly every facet of metazoan life. Representatives of all six classical nuclear receptor superfamily members were present before the protostome–deuterostome split, more than 700 million years ago. Nuclear receptor sequence and structure diversification to accommodate ligand binding has occurred numerous times, with the earliest report of steroid‐hormone binding occurring in the Annelid and of retinoic acid in the lower metazoan phylum Cnidaria. During the Cambrian period a quadruplication of the genome leading to jawed vertebrates gave rise to many of the nuclear receptor paralogues present today.

Key Concepts:

  • The evolutionary origins and diversification of the nuclear receptor superfamily gene structure in the Metazoa.

  • Nuclear receptors are unique to the metazoan kingdom.

  • Members of the nuclear receptor superfamily are present in all extant phyla of metazoans.

  • Representatives of six classical nuclear receptor superfamily members were present before the proteosome–deutrosome division more than 700 million years ago.

  • During the Cambrian period a quadruplication of the genome giving rise to jawed vertebrates occurred producing many of the nuclear receptor paralogues present today.

Keywords: nuclear receptor; steroid hormone; Cambrian period; molecular exploitation; Metazoa; placozoa

Figure 1.

(a) A schematic representation of the metazoan family tree, showing the potential branching points of the last common ancestors between each phylum. (b) The six subfamilies of the nuclear receptor (NR) superfamily. A consensus phylogenetic tree demostrating the distribution of representative nuclear receptor members in the Metazoa and their distribution into six subfamilies. This figure uses the trivial names of the NRs. For a complete list of the corresponding new nomenclature see Nuclear Receptors Committee or the Nuclear Receptor Nomenclature Home page. This phylogenetic tree was constructed using the ClustalX program v2.0 with the near‐neighbour joining method. From top to bottom the accession numbers are: XP_779976, P13631, BAA25569, NP_001071806, NP_001123279, AAF57280, XP_001636937, NP_775180, CAA61534, AAL29199, XP_001619117, XP_001634258, XP_001632045, AAL29194, ACF16007, ABI97120, BAE06416, P11474, AAU88062, NP_001135406, XP_002117374, XP_001636637, XP_002117375, XP_001624292, NP_001122483, XP_001631058, AAL29201, AAL29196, XP_002109806, XP_002159396, BAE06356, AAF54774, XP_001944021, XP_001629708, AAL29200, AAF57091, XP_002154441, XP_001624815, XP_001634999, AAF52303, XP_780706, ACG76360, XP_001630385, AAP79295, XP_001630386, AAL29193, AAC80008, NP_476781, BAE06678, XP_002109459, BAF85823, AAW34268, NP_001097126, BAE06492, XP_001638550, XP_002159483, CAA61134, XP_002115810, ACA04755, CAD57002, NP_730359, ACH68437, XP_001179003, BAE06474, NP_001024953, CAA06670.

Figure 2.

Structural homology of the retinoic acid receptor (RAR). Alignment of the human RAR paralogues, alpha (a), beta (b) and gamma (g), and the RAR isolated from the urochordate Polyandrocarpa misakiensis (accession number BAA25569). The boxes represent the location of functional domains within the nuclear receptor. Numerical representation given below the alignment relates to the homology for each domain between the human RAR paralogues and between the three paralogues and the urochordate RAR. This global multiple sequence alignment was generated using the ClustalX program v2.0.

Figure 3.

Retinoic acid receptor (RAR) and retinoic acid X‐receptor (RXR) in different metazoans. The presence of assayed RAR and RXR genes is shown in coloured boxes. The information given in this figure is based on BLAST search results, which have been verified by phylogenetic analyses. Modified with permission from Campo‐Paysaa et al..

Figure 4.

Model of NR subfamily III evolution. Steroid hormone receptors originated from a duplication of an ancient ER. This hypothetical receptor represented as PR/CR ancestor, duplicated and gave rise to the PR and CR which are present in the lamprey and then duplicated once more to give the PR, GR, MR and AR present in terrestrial vertebrates. A further genome‐level duplication event occurred within the teleost lineage. ERR refers to oestrogen‐related receptor; ER, oestrogen receptor; PR, progesterone receptor; CR, corticoid receptor; AR, androgen receptor; GR, glucocorticoid receptor and MR, mineralocorticoid receptor.



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Further Reading

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Villena JA, Hock MB, Chang WY et al. (2007) Orphan nuclear receptor estrogen‐related receptor alpha is essential for adaptive thermogenesis. Proceedings of the National Academy of Sciences of the USA 104: 1418–1423.

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Sáez, Pablo J, Lange, Soledad, Pérez‐Acle, Tomas, and Owen, Gareth I(Jan 2010) Nuclear Receptor Genes: Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0006145.pub3]