title: Discovery of the elusive leptin in birds: identification of several 'missing links' in the evolution of leptin and its receptor.
abstract: Leptin is a pleiotropic protein best known for regulation of appetite and fat storage in mammals. While many leptin orthologs have been identified among vertebrates, an authentic leptin in birds has remained elusive and controversial. Here we identify leptin sequence from the Peregrine falcon, Falco peregrinus (pfleptin), and identify sequences from two other birds (mallard and zebra finch), and 'missing' vertebrates (elephant shark, alligator, Indian python, Chinese soft-shelled turtle, and coelacanth). The pattern of genes surrounding leptin (snd1, rbm28) is syntenic between the falcon and mammalian genomes. Phylogenetic analysis of all known leptin protein sequences improves our understanding of leptin's evolution. Structural modeling of leptin orthologs highlights a highly conserved hydrophobic core in the four-helix cytokine packing domain. A docked model of leptin with the leptin receptor for Peregrine falcon reveals several conserved amino acids important for the interaction and possible coevolution of leptin with its receptor. We also show for the first time, an authentic avian leptin sequence that activates the JAK-STAT signaling pathway. These newly identified sequences, structures, and tools for avian leptin and its receptor will allow elucidation of the function of these proteins in feral and domestic birds.
authors.affiliation: Integrated Biosciences Program, The University of Akron, Akron, Ohio, United States of America; Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Prokop
authors.affiliation: Integrated Biosciences Program, The University of Akron, Akron, Ohio, United States of America.
authors.forename: Cameron
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Integrated Biosciences Program, The University of Akron, Akron, Ohio, United States of America.
authors.forename: Donald
authors.initials: D
authors.lastname: Gasper
authors.affiliation: Integrated Biosciences Program, The University of Akron, Akron, Ohio, United States of America.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Duff
authors.affiliation: Integrated Biosciences Program, The University of Akron, Akron, Ohio, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Milsted
authors.affiliation: College of Agriculture, Ibaraki University, Amimachi, Ibaraki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ohkubo
authors.affiliation: Integrated Biosciences Program, The University of Akron, Akron, Ohio, United States of America.
authors.forename: Hope C
authors.initials: HC
authors.lastname: Ball
authors.affiliation: Integrated Biosciences Program, The University of Akron, Akron, Ohio, United States of America.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Shawkey
authors.affiliation: Geier Collections and Research Center, Cincinnati Museum Center, Cincinnati, Ohio, United States of America.
authors.forename: Herman L
authors.initials: HL
authors.lastname: Mays
authors.affiliation: Animal and Food Sciences, University of Delaware, Newark, Delaware, United States of America.
authors.forename: Larry A
authors.initials: LA
authors.lastname: Cogburn
authors.affiliation: Integrated Biosciences Program, The University of Akron, Akron, Ohio, United States of America.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Londraville
mesh_terms: D000818:Animals; D001717:Birds / Q000235:genetics*; D019143:Evolution, Molecular; D020738:Leptin / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D010802:Phylogeny; D054411:Receptors, Leptin / Q000737:chemistry / Q000235:genetics; D012104:Reptiles / Q000235:genetics; D020539:Sequence Analysis, Protein
chemical_list: D020738:Leptin; D054411:Receptors, Leptin