Nuclear hormone receptors and evolution

Abstract

SYNOPSIS. The nuclear receptor (NR) superfamily includes, in addition to ligandactivated transcription factors, members called orphan receptors, for which no ligand has yet been identified. Phylogenetic analysis shows that the nuclear receptor superfamily can be split into six subfamilies. Interestingly, there appears to be no relationship between the position of a given liganded receptor in the tree and the chemical nature of its ligand. For example, RAR and RXR, which both recognize retinoids, belong to two different subfamilies, suggesting an independence between the evolutionary history of the receptors and their ligand binding abilities. A .PCR screen for the presence of NR genes in several phyla of early- and nonmetazoan organisms suggests that NR are specific to metazoans and also reveals that the NR genes in Hydra or Anemonia appear to be limited to homologues of orphan receptors. Taken together these data suggest that the first members of the superfamily were probably orphan receptors that later on gained the ability to bind a ligand. Finally, we observed that SmFTZ-Fl and SmRXR are expressed at different levels along the life cycle of the parasitic flatworm Schistosoma mansoni. This suggests that these receptors may play a role in the control of the development of this organism.