title: Evolutionary pattern in the OXT-OXTR system in primates: coevolution and positive selection footprints.
abstract: Oxytocin is a nonapeptide involved in a wide range of physiologic and behavioral functions. Until recently, it was believed that an unmodified oxytocin sequence was present in all placental mammals. This study analyzed oxytocin (OXT) in 29 primate species and the oxytocin receptor (OXTR) in 21 of these species. We report here three novel OXT forms in the New World monkeys, as well as a more extensive distribution of a previously described variant (Leu8Pro). In structural terms, these OXTs share the same three low-energy conformations in solution during molecular dynamic simulations, with subtle differences in their side chains. A consistent signal of positive selection was detected in the Cebidae family, and OXT position 8 showed a statistically significant (P = 0.013) correlation with litter size. Several OXTR changes were identified, some of them promoting gain or loss of putative phosphorylation sites, with possible consequences for receptor internalization and desensitization. OXTR amino acid sites are under positive selection, and intramolecular and intermolecular coevolutionary processes with OXT were also detected. We suggest that some New World monkey OXT-OXTR forms can be correlated to male parental care through the increase of cross-reactivity with its correlated vasopressin system.
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil;
authors.forename: Pedro
authors.initials: P
authors.lastname: Vargas-Pinilla
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil;
authors.forename: Vanessa Rodrigues
authors.identifier: http://orcid.org/0000-0003-2677-0903
authors.initials: VR
authors.lastname: Paixão-Côrtes
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil;
authors.forename: Pamela
authors.initials: P
authors.lastname: Paré
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil;
authors.forename: Luciana
authors.initials: L
authors.lastname: Tovo-Rodrigues
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil;
authors.forename: Carlos Meton de Alencar Gadelha
authors.initials: CM
authors.lastname: Vieira
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil;
authors.forename: Agatha
authors.initials: A
authors.lastname: Xavier
authors.affiliation: Institut de Biologia Evolutiva, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain;
authors.forename: David
authors.initials: D
authors.lastname: Comas
authors.affiliation: Centro de Primatologia do Rio de Janeiro, 20940-200 Rio de Janeiro, RJ, Brazil; and.
authors.forename: Alcides
authors.initials: A
authors.lastname: Pissinatti
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil;
authors.forename: Marialva
authors.initials: M
authors.lastname: Sinigaglia
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil;
authors.forename: Maurício Menegatti
authors.initials: MM
authors.lastname: Rigo
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil;
authors.forename: Gustavo Fioravanti
authors.initials: GF
authors.lastname: Vieira
authors.affiliation: Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil.
authors.forename: Aldo B
authors.initials: AB
authors.lastname: Lucion
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil; francisco.salzano@ufrgs.br maria.bortolini@ufrgs.br.
authors.forename: Francisco Mauro
authors.initials: FM
authors.lastname: Salzano
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil; francisco.salzano@ufrgs.br maria.bortolini@ufrgs.br.
authors.forename: Maria Cátira
authors.initials: MC
authors.lastname: Bortolini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D008297:Male; D008969:Molecular Sequence Data; D010121:Oxytocin / Q000737:chemistry / Q000235:genetics*; D011323:Primates / Q000235:genetics*; D018045:Receptors, Oxytocin / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D018045:Receptors, Oxytocin; D010121:Oxytocin
keywords: OXT; OXTR; behavior; coevolution; primates