“…Interestingly, in both cases these protostome receptors do not bind the bona fide vertebrate ligand suggesting a more complex history than anticipated. Indeed the ligand binding evolution of estrogen receptor is still far from understood (see contrasting views in Baker, 2003, Thornton et al, 2003and Paris et al, 2008b and similar questions are suggested by the recent characterization of thyroid hormone receptors in platyhelminthes, molluscs or even in a deuterostome, the cephalochordate amphioxus (Wu et al, 2007, Paris et al, 2008a. At a much smaller taxonomic level the careful analysis of the ligand-binding specificity of PXR in mammals also provides an example of shifts in the ligandbinding ability of a nuclear receptor (Krasowski et al, 2005 ;Reschly et al, 2007).…”