The amphioxus genome enlightens the evolution of the thyroid hormone signaling pathway

Abstract

Thyroid hormones (THs) have pleiotropic effects on vertebrate development, with amphibian metamorphosis as the most spectacular example. However, developmental functions of THs in non-vertebrate chordates are largely hypothetical and even TH endogenous production has been poorly investigated. In order to get better insight into the evolution of the thyroid hormone signaling pathway in chordates, we have taken advantage of the recent release of the amphioxus genome. We found amphioxus homologous sequences to most of the genes encoding proteins involved in thyroid hormone signaling in vertebrates, except the fast-evolving thyroglobulin: sodium iodide symporter, thyroid peroxidase, deiodinases, thyroid hormone receptor, TBG, and CTHBP. As only some genes encoding proteins involved in TH synthesis regulation were retrieved (TRH, TSH receptor, and CRH receptor but not their corresponding receptors and ligands), there may be another mode of upstream regulation of TH synthesis in amphioxus. In accord with the notion that two whole genome duplications took place at the base of the vertebrate tree, one amphioxus gene often corresponded to several vertebrate homologs. However, some amphioxus specific duplications occurred, suggesting that several steps of the TH pathway were independently elaborated in the cephalochordate and vertebrate lineages. The present results therefore indicate that amphioxus is capable of producing THs. As several genes of the TH signaling pathway were also found in the sea urchin genome, we propose that the thyroid hormone signaling pathway is of ancestral origin in chordates, if not in deuterostomes, with specific elaborations in each lineage, including amphioxus.

Iodothyronine deiodinases: a functional and evolutionary perspective

“…Indeed, current information supports the notion that the vertebrate thyroid gland, as well as the endostyle and subpharyngeal gland in invertebrate chordates, may have evolved from a common ancestor (for review Kluge et al (2005) and Paris et al (2008)). Thus, the genomes of cephalochordates (amphioxus) and urochordates (tunicates) contain orthologs of the main genes involved in thyroid hormonogenesis and the TH-signaling pathway (Na/I symporter, thyroid peroxidase, deiodinase, and TH receptor), but they lack the components for neuroendocrine control of the thyroid (for review : Holland et al (2008) and Paris et al (2008)). In the ascidian Halocynthia roretzy, at least one deiodinase homolog (hrDx) has been biochemically characterized.…”

The evolution of the ligand/receptor couple: A long road from comparative endocrinology to comparative genomics

“…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).…”

“…Among the several possible explanations we propose that: (i) the molecule used for the treatment is metabolized to another compound that is the active one. Indeed we recently discovered such a situation in amphioxus, where thyroid hormones are metabolized to a compound that binds the TR (Paris et al, 2008a) ; (ii) a NR that binds estrogen exists but this is not an orthologue of ER ; (iii) the effect of estrogen is mediated by another receptor system, e.g. a transmembrane receptor (see Revankar et al, 2005 for an example) or a cytoplasmic protein such as in the case of Glomus discussed above.…”

Iodothyronine Deiodinases: Key Enzymes Behind the Action of Thyroid Hormone

“…Indeed, this enzyme contains a SeCys residue like vertebrate deiodinases, and its catalytic activity resembles vertebrate D1 (Shepherdley et al, 2004). Furthermore, some authors (Paris et al 2008a) have reported existence of deiodinase-like proteins in animals even more primitive than the cephalochordates such as the sea urchin Strongylocentrotus purpuratus, a non-chordate deuterostome, which deserves detailed studies including substrate specificity and other biochemical characterizations of this sea urchin protein. Taken together, although we do not have evidence yet that extant deiodinase of the amphioxus bfDy has close connection with ancestral D1, nor do we know to what extent the deiodinase-like protein of the sea urchin affects its thyroid hormone-signaling system, the peculiar substrate specificity of extant vertebrate D1 may be better interpreted in view of the history of the molecular evolution of thyroid hormones, thyroid hormone receptors and deiodinases.…”

“…6). The genome sequence of amphioxus, a cephalochordate, was already released (Putnam et al, 2008) and a set of proteins necessary for thyroid hormone production, secretion, circulation and cellular signaling have been revealed encoded in the amphioxus genome (Paris et al, 2008a). To date, an amphioxus Branchiostoma floridae deiodinase named bfDy has been biochemically characterized.…”