Nuclear hormone receptors and evolution

The nuclear receptor (NR) superfamily includes, in addition to ligand-activ ated transcription factors, members called orphan receptors, for which no l igand has yet been identified. Phylogenetic analysis shows that the nuclear receptor superfamily can be split into six subfamilies, Interestingly, the re appears to be no relationship between the position of a given liganded r eceptor in the tree and the chemical nature of its ligand, For example, RAR and RXR, which both recognize retinoids, belong to two different subfamili es, suggesting an Independence between the evolutionary history of the rece ptors and their ligand binding abilities, A PCR screen for the presence of NR genes in several phyla of early- and non-metazoan organisms suggests tha t 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 t ogether these data suggest that the first members of the superfamily were p robably orphan receptors that later on gained the ability to bind a ligand. Finally, we observed that SmFTZ-F1 and SmRXR are expressed at different le vels along the life cycle of the parasitic flatworm Schistosoma mansoni. Th is suggests that these receptors may play a role in the control of the deve lopment of this organism.