Evolutionary Origin of a Functional Gonadotropin in the Pituitary of the most Primitive Vertebrate, Hagfish

Abstract

Hagfish, which lack both jaws and vertebrae, are considered themost primitive vertebrate known, living or extinct. Hagfish havelong been the enigma of vertebrate evolution not only becauseof their evolutionary position, but also because of our lack ofknowledge on fundamental processes. Key elements of the re-productive endocrine system in hagfish have yet to be elucidated.Here, the presence and identity of a functional glycoprotein hor-mone (GPH) have been elucidated from the brown hagfish Para-myxine atami. The hagfish GPH consists of two subunits, α and β,which are synthesized and colocalized in the same cells of theadenohypophysis. The cellularand transcriptional activitiesof hag-fish GPHα and -β were significantly correlated with the develop-mental stages of the gonad. The purified native GPH induced thereleaseofgonadalsexsteroidsinvitro.Fromourphylogeneticanal-ysis, we propose that ancestral glycoprotein α-subunit 2 (GPA2)and β-subunit 5 (GPB5) gave rise to GPHα and GPHβ of the verte-brate glycoprotein hormone family, respectively. The identifiedhagfishGPHαand-βsubunitsappeartobethetypicalgnathostomeGPHαand-βsubunitsbasedonthesequenceandphylogeneticanal-yses.WehypothesizethattheidentityofasinglefunctionalGPHofthehagfish,hagfishGTH,providescriticalevidencefortheexistenceof a pituitary-gonadal system in the earliest divergent vertebratethat likely evolved from an ancestral, prevertebrate exclusivelyneuroendocrine mechanism by gradual emergence of a previouslyundescribed control level, the pituitary, which is not found inthe Protochordates.