Meeting Abstract
Glycoprotein hormones (GPH) and their receptors are classic models of protein co-evolution. Members of these heterodimeric hormone/ receptor protein complexes evolved following gene duplication events to interact with specific protein partners and mediate hypothalamic – pituitary – peripheral gland endocrine signaling. Vertebrates typically have three functionally distinct GPH mediated endocrine signaling complexes, two gonadotropins, luteinizing hormone and follicle stimulating hormone, and one thyroid stimulating hormone. Each hormone is a heterodimer consisting of a common alpha subunit bound to one of three different beta subunits that recognize specific G-protein coupled receptors. This type of endocrine signaling originated at the base of the chordate lineage with agnathans having a subset of hormone subunits and receptors, recently characterized in the sea lamprey. Genome sequencing projects reveal that the cephalochordate, amphioxus, has a single receptor as well as single alpha and beta hormone subunits, and the holocephalan, elephant shark, genome encodes members of all three endocrine signaling complexes. These genome assemblies help define the historical intervals and gene duplication mechanisms by which the protein families have diversified. We use reporter gene based functional assays of the amphioxus and elephant shark receptors and their hormones to understand the molecular mechanisms by which these protein families have co-evolved to form specific partnerships. Our results characterize the early evolution of endocrine signaling complexes following gene duplication events that occurred prior to the divergence of Chondrichthyes from the chordate lineage.
