Open Access Research article

The fate of the duplicated androgen receptor in fishes: a late neofunctionalization event?

Véronique Douard1, Frédéric Brunet2, Bastien Boussau3, Isabelle Ahrens-Fath4, Virginie Vlaeminck-Guillem2, Bernard Haendler4, Vincent Laudet2* and Yann Guiguen1

Author Affiliations

1 INRA-SCRIBE IFR 140, Campus de Beaulieu, 35042 Rennes Cedex, France

2 Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, UMR 5242 du CNRS, INRA, IFR128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, 46, Allée d'Italie, 69364 Lyon Cedex 07, France

3 Biométrie et Biologie Évolutive UMR CNRS 5558 Université Claude Bernard-Lyon 1, 43, Boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex, France

4 Bayer Schering Pharma AG, 13342 Berlin, Germany

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BMC Evolutionary Biology 2008, 8:336  doi:10.1186/1471-2148-8-336

Published: 18 December 2008

Abstract

Background

Based on the observation of an increased number of paralogous genes in teleost fishes compared with other vertebrates and on the conserved synteny between duplicated copies, it has been shown that a whole genome duplication (WGD) occurred during the evolution of Actinopterygian fish. Comparative phylogenetic dating of this duplication event suggests that it occurred early on, specifically in teleosts. It has been proposed that this event might have facilitated the evolutionary radiation and the phenotypic diversification of the teleost fish, notably by allowing the sub- or neo-functionalization of many duplicated genes.

Results

In this paper, we studied in a wide range of Actinopterygians the duplication and fate of the androgen receptor (AR, NR3C4), a nuclear receptor known to play a key role in sex-determination in vertebrates. The pattern of AR gene duplication is consistent with an early WGD event: it has been duplicated into two genes AR-A and AR-B after the split of the Acipenseriformes from the lineage leading to teleost fish but before the divergence of Osteoglossiformes. Genomic and syntenic analyses in addition to lack of PCR amplification show that one of the duplicated copies, AR-B, was lost in several basal Clupeocephala such as Cypriniformes (including the model species zebrafish), Siluriformes, Characiformes and Salmoniformes. Interestingly, we also found that, in basal teleost fish (Osteoglossiformes and Anguilliformes), the two copies remain very similar, whereas, specifically in Percomorphs, one of the copies, AR-B, has accumulated substitutions in both the ligand binding domain (LBD) and the DNA binding domain (DBD).

Conclusion

The comparison of the mutations present in these divergent AR-B with those known in human to be implicated in complete, partial or mild androgen insensitivity syndrome suggests that the existence of two distinct AR duplicates may be correlated to specific functional differences that may be connected to the well-known plasticity of sex determination in fish. This suggests that three specific events have shaped the present diversity of ARs in Actinopterygians: (i) early WGD, (ii) parallel loss of one duplicate in several lineages and (iii) putative neofunctionalization of the same duplicate in percomorphs, which occurred a long time after the WGD.