title: Loss of neurturin in frog--comparative genomics study of GDNF family ligand-receptor pairs.
abstract: Four different GDNF family ligand (GFL)-receptor (GFRalpha) binding pairs exist in mammals, and they all signal via the RET receptor tyrosine kinase. However, the evolution of these molecules is poorly understood. We identified orthologs of all four GFRalpha receptors and GRAL (GDNF Receptor Alpha-Like) in all vertebrate classes, and a predicted GFR-like protein in several invertebrates. In addition, Gas1 (growth arrest-specific 1), a distant member of the GFR-superfamily, is present in both vertebrates and invertebrates. Analysis of exon structures suggests a common origin of GFR-superfamily proteins and early divergence of Gas1 from the common ancestor. Bony fishes have orthologs of all four mammalian GFLs, consistent with genome duplications in early vertebrates. Surprisingly, the clawed frog and chicken have only three GFLs: synteny analysis indicates loss of neurturin in frog and of persephin in chicken. Evolutionary trace analysis and protein structure homology modeling points at GDNF as the endogenous ligand of frog GFRalpha2.
authors.affiliation: Institute of Biotechnology, 00014 University of Helsinki, Finland.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Hätinen
authors.forename: Liisa
authors.initials: L
authors.lastname: Holm
authors.forename: Matti S
authors.initials: MS
authors.lastname: Airaksinen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura; D023281:Genomics; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000502:physiology*; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051101:Neurturin / Q000378:metabolism*; D010802:Phylogeny; D016415:Sequence Alignment
chemical_list: D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051098:Glial Cell Line-Derived Neurotrophic Factors; D051101:Neurturin