Nuclear receptors are markers of animal genome evolution

  • Héctor Escrivá García
  • Vincent Laudet
  • Marc Robinson-Rechavi


Nuclear hormone receptors form one evolutionary related super-family of proteins, which mediate the interaction between hormones (or other ligands) and gene expression in animals. Early phylogenetic analyses showed two main periods of gene duplication which gave rise to present-day diversity in most animals: one at the origin of the family, and another specifically in vertebrates. Moreover this second period is composed itself by, probably, two rounds of duplication, as proposed by Susumu Ohno at the origin of vertebrates. There are indeed often two, three or four vertebrate orthologs of each invertebrate nuclear receptor, in accordance with this theory. The complete genome of Drosophila melanogaster contains 21 nuclear receptors, compared to 49 in the human genome. In addition, many nuclear receptors have more paralogs in the zebrafish than in mammals, and a genome duplication has been proposed at the origin of ray-finned fishes. Nuclear receptors are a very good model to investigate the dating and functional role of these duplications, since they are dispersed in the genome, allow robust phylogenetic reconstruction, and are functionnaly well characterized, with different adaptations for different paralogs. We illustrate this with examples from differents nuclear receptors and different groups of species.

Key words

animal evolution domain duplication hormone phylogeny receptor transcription factor vertebrate evolution 


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  1. Adams, M.D., Celniker, S.E., Holt, R.A., Evans, CA., Gocayne, J.D., Amanatides, P.G., Scherer, S.E., Li, P.W., Hoskins, R.A., Galle, R.F., George, R.A., Lewis, S.E., Richards, S., Ashburner, M., Henderson, S.N., Sutton, G.G., Wortman, J.R., Yandell, M.D., Zhang, Q., Chen, L.X., Brandon, R.C., Rogers, Y.H., Blazej, R.G., Champe, M., Pfeiffer, B.D., Wan, K.H., Doyle, C., Baxter, E.G., Helt, G., Nelson, C.R., Gabor, G.L., Abril, J.F., Agbayani, A., An, H.J., Andrews-Pfannkoch, C., Baldwin, D., Bailew, R.M., Basu, A., Baxendale, J., Bayraktaroglu, L., Beasley, E.M., Beeson, K.Y., Benos, P.V., Berman, B.P., Bhan-dari, D., Bolshakov, S., Borkova, D., Botchan, M.R., Bouck, J., et al. (2000). The genome sequence of drosophila melanogaster. Science 287, 2185–2195.PubMedCrossRefGoogle Scholar
  2. Amero, S.A., Kretsinger, R.H., Moncrief, N.D., Yamamoto, K.R. and Pearson, W.R. (1992). The origin of nuclear receptor proteins: A single precursor distinct from other transcription factors. Mol. Endocrinol 6, 3–7.PubMedCrossRefGoogle Scholar
  3. Amores, A., Force, A., Yan, Y.L., Joly, L., Amemiya, C., Fritz, A., Ho, R.K., Langeland, J., Prince, V., Wang, Y.L., Westerfield, M., Ekker, M. and Postlethwait, J.H. (1998). Zebrafish hox clusters and vertebrate genome evolution. Science 282, 1711–1714.PubMedCrossRefGoogle Scholar
  4. Caron, H., van Schaik, B., van der Mee, M., Baas, F., Riggins, G., van Sluis, P., Hermus, M.-C., van Asperen, R., Boon, K., Voûte, P.A., Heisterkamp, S., van Kampen, A. and Versteeg, R. (2001). The human transcriptome map: Clustering of highly expressed genes in chromosomal domains. Science 291, 1289–1292.PubMedCrossRefGoogle Scholar
  5. Desvergne, B. and Wahli, W. (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocrine Rev. 20, 649–688.CrossRefGoogle Scholar
  6. Dunham, I., Shimizu, N., Roe, B.A., Chissoe, S., Hunt, A.R., Collins, J.E., Bruskiewich, R., Beare, D.M., Clamp, M., Smink, L.J., Ainscough, R., Almeida, J.P., Babbage, A., Bagguley, C., Bailey, J., Barlow, K., Bates, K.N., Beasley, O., Bird, C.P., Blakey, S., Bridgeman, A.M., Buck, D., Burgess, J., Burrill, W.D., O’Brien, K.P. and et al. (1999). The DNA sequence of human chromosome 22. Nature 402, 489–495.PubMedCrossRefGoogle Scholar
  7. Escriva, H., Delaunay, F. and Laudet, V. (2000). Ligand binding and nuclear receptor evolution. BioEssays 22, 717–727.PubMedCrossRefGoogle Scholar
  8. Escriva, H., Holland, N.D., Gronemeyer, H., Laudet, V. and Holland, L.Z. (2002a). The retinoic acid signaling pathway regulates anterior/posterior patterning in the nerve cord and pharynx of amphioxus, a chordate lacking neural crest. Development, in press.Google Scholar
  9. Escriva, H., Manzon, L., Youson, J., Laudet, V. (2002b) Analysis of lamprey and hagfish genes reveals a complex history of gene duplications during early vertebrate evolution. Mol. Biol. Evol., 19, 1440–1450.PubMedCrossRefGoogle Scholar
  10. Escriva, H., Safi, R., Hänni, C., Langlois, M.-C., Saumitou-La-prade, P., Stehelin, D., Capron, A., Pierce, R. and Laudet, V. (1997). Ligand binding was aquired during evolution of nuclear receptors. Proc. Natl. Acad. Sci. USA 94, 6803–6808.PubMedCrossRefGoogle Scholar
  11. Fairclough, L. and Tata, J.R. (1997) An immunocytochemical analysis of the expression of thyroid hormone receptor alpha and beta proteins during natural and thyroid hormone-induced metamorphosis in Xenopus. Dev. Growth Differ. 39, 273–283.PubMedCrossRefGoogle Scholar
  12. Force, A., Lynch, M., Pickett, F.B., Amores, A., Yan, Y.-l. and Postlethwait, J. (1999). Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151, 1531–1545.PubMedGoogle Scholar
  13. Hattori, M., Fujiyama, A., Taylor, T.D., Watanabe, H., Yada, T., Park, H.S., Toyoda, A., Ishii, K., Totoki, Y., Choi, D.K., Soeda, E., Ohki, M., Takagi, T., Sakaki, Y, Taudien, S., Blechschmidt, K., Polley, A., Menzel, U., Delabar, J., Kumpf, K., Lehmann, R., Patterson, D., Reichwald, K., Rump, A., Schillhabel, M., Schudy, A., Zimmermann, W., Rosenthal, A., Kudoh, J., Schibuya, K., Kawasaki, K., Asakawa, S., Shintani, A., Sasaki, T., Nagamine, K., Mitsuyama, S., Antonarakis, S.E., Minoshima, S., Shimizu, N., Nordsiek, G., Hornischer, K., Brant, P., Scharfe, M., Schon, O., Desario, A., Reichelt, J., Kauer, G., Blocker, H., Ramser, J., Beck, A., Klages, S., Hennig, S., Riesselmann, L., Dagand, E., Haaf, T., Wehrmeyer, S., Borzym, K., Gardiner, K., Nizetic, D., Francis, F., Lehrach, H., Reinhardt, R. and Yaspo, M.L. (2000). The DNA sequence of human chromosome 21. Nature 405, 311–319.PubMedCrossRefGoogle Scholar
  14. Holland, P. (2002) More genes in vertebrates? In Genome Evolution, (Eds. Meyer, A. Meyer and van de Peer, Y), Kluwer Academic Publishers, Dordrecht, in press.Google Scholar
  15. Hughes, A.L. and Friedman, R. (2002) 2R or not 2R: testing hypotheses of genome duplication in early vertebrates. In Genome Evolution (Eds. Meyer, A. and van de Peer, Y), Kluwer Academic Publishers, Dordrecht, in press.Google Scholar
  16. Laudet, V. (1997). Evolution of the nuclear receptor superfamily: Early diversification from an ancestral orphan receptor. J. Mol. Endocrinol. 19, 207–226.PubMedCrossRefGoogle Scholar
  17. Laudet, V. and Gronemeyer, H. (2002) The Nuclear Receptors Factsbook, Academic Press, London.Google Scholar
  18. Laudet, V., Hänni, C., Coll, J., Catzeflis, C. and Stéhelin, D. (1992). Evolution of the nuclear receptor gene family. EMBO J. 11, 1003–1013.PubMedGoogle Scholar
  19. Le Jossic, C. and Michel, D. (1998). Striking evolutionary conservation of a cis-element related to nuclear receptor target sites and present in tr2 orphan receptor genes. Biochem. Biophys. Res. Commun. 245, 64–69.PubMedCrossRefGoogle Scholar
  20. Lundin, L.-G., Larhammar, D. et al. (2002) Numerous groups of chromosomal regional paralogies strongly indicate two genome doublings at the root of vertebrates. In Genome Evolution (Eds. Meyer, A. and van de Peer, Y), Kluwer Academic Publishers, Dordrecht, in press.Google Scholar
  21. Maglich, J.M., Sluder, A.E., Guan, X., Shi, Y., McKee, D.D., Carrick, K., Kamdar, K., Willson, T.M. and Moore, J.T. (2001). Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drosophila genomes. 2, research0029.0021-0027.Google Scholar
  22. Mâlaga-Trillo, E. and Meyer, A. (1) Genome duplications and accelerated evolution of Hox genes and cluster architecture in teleost fishes. Amer. Zool., 41: 676–686.Google Scholar
  23. Mendonça, R.L., Escriva, H., Vanacker, J.-M., Bouton, D., Delan-noy, S., Pierce, R., Laudet, V. (1999) Nuclear hormone receptors and evolution. Amer. Zool. 39, 704–713.Google Scholar
  24. Nuclear Receptors Nomenclature Committee (1999). A unified nomenclature system for the nuclear receptor superfamily. Cell 97, 161–163.CrossRefGoogle Scholar
  25. Ohno, S. (1970) Evolution by Gene Duplication. Springer-Verlag, New York, NY.Google Scholar
  26. Postlethwait, J.H., Woods, I.G., Ngo-Hazelett, P., Yan, Y.L., Kelly, P.D., Chu, F., Huang, H., Hill-Force, A. and Talbot, W.S. (2000). Zebrafish comparative genomics and the origins of vertebrate chromosomes. Genome Res. 10, 1890–1902.PubMedCrossRefGoogle Scholar
  27. Robinson-Rechavi, M., Marchand, O., Escriva, H., Bardet, P.-L., Zelus, D., Hughes, S. and Laudet, V. (2001a). Euteleost fish genomes are characterized by expansion of gene families. Genome Res. 11, 781–788.PubMedCrossRefGoogle Scholar
  28. Robinson-Rechavi, M., Carpentier, A.-S., Duffraisse, M. and Laudet, V. (2001b). How many nuclear hormone receptors in the human genome? Trends Genet. 17, 554–556.PubMedCrossRefGoogle Scholar
  29. Robinson-Rechavi, M., Marchand, O., Escriva, H. and Laudet, V. (2001c). An ancestral whole-genome duplication may not have been responsible for the abundance of duplicated fish genes. Curr. Biol. 11, R458–R459.PubMedCrossRefGoogle Scholar
  30. Robinson-Rechavi, M., Marchand, O., Escriva, H. and Laudet, V. (2002d). Re: Revisiting recent challenges to the ancient fish-specific genome duplication hypothesis. Curr. Biol. 11, R1007–R1008.CrossRefGoogle Scholar
  31. Shimeld, S.M. (1996) Retinoic acid, HOX genes and the anterior posterior axis in chordates. BioEssays 18, 613–616.CrossRefGoogle Scholar
  32. Suga, H., Koyanagi, M., Hoshiyama, D., Ono, K., Iwabe, N., Kuma, K. and Miyata, T. (1999). Extensive gene duplication in the early evolution of animals before the parazoan-eumetazoan split demonstrated by g proteins and protein tyrosine kinases from sponge and hydra. J. Mol. Evol. 48, 646–653.PubMedCrossRefGoogle Scholar
  33. Taylor, J.S., Van de Peer, Y., Braasch, I. and Meyer, A. (2001a). Comparative genomics provides evidence for an ancient genome duplication event in fish. Phil. Trans. R. Soc. Lond. Ser. B 356, 1661–1679.CrossRefGoogle Scholar
  34. Taylor, J.S., van de Peer, Y and Meyer, A. (2001b). Revisiting recent challenges to the ancient fish-specific genome duplication hypothesis. Curr. Biol. 11, R1005–R1007.PubMedCrossRefGoogle Scholar
  35. Thornton, J.W. (2001). Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. Proc. Natl. Acad. Sci. USA 98, 5671–5676.PubMedCrossRefGoogle Scholar
  36. Thornton, J.W. and Desalle, R. (2000). A new method to localize and test the significance of incongruence: Detecting domain shuffling in the nuclear receptor superfamily. Syst. Biol. 49, 183–201.PubMedCrossRefGoogle Scholar
  37. Wicker, N. Perrin, G.R., Thierry, J.C. and Poch, O. (2001). Secator: A program for inferring protein subfamilies from phylogenetic trees. Mol Biol Evol 18, 1435–1441.PubMedCrossRefGoogle Scholar
  38. Yamano, K. and Miwa, S. (1998) Differential gene expression of thyroid hormone receptor α and β in fish development. Gen. Comp. Endocrinol. 109, 75–85.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • Héctor Escrivá García
    • 1
  • Vincent Laudet
    • 1
  • Marc Robinson-Rechavi
    • 1
  1. 1.Laboratoire de Biologie Moléculaire et CellulaireEcole Normale Supérieure de LyonLyon cedex 07France

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