Origin and evolution of the Trk family of neurotrophic receptors

Among the numerous tyrosine kinase receptors, those belonging to the Trk family are distinctively involved in the development of complex traits within the vertebrate nervous system. Until recently, the lack of a proper Nt/Trk system in invertebrates has lead to the belief that they were a vertebrate innovation. Recent data, however, have challenged the field, and proved that bona fide Trk Receptors do exist in invertebrates. Here, we review and discuss the evolutionary history of the Trk Receptor family, and draw a comprehensive scenario that situates the origin of the Nt/Trk signalling prior to the origin of vertebrates. Probably, a ProtoTrk receptor was invented by means of domain and exon shuffling from pieces of ancient genes, generating the unique combination of domains found in extant Trk Receptors. It is suggestive to propose that subtle protein mutations, gene duplications, and co-options in particular territories of a primitive Nt/Trk system were instrumental to the development of a complex vertebrate nervous system.