Functional characteristics of four primate oxytocin receptors: relationships to biparental care and social monogamy

Advisor Information

Jeffrey French

Location

Dr. C.C. and Mabel L. Criss Library

Presentation Type

Poster

Start Date

2-3-2018 12:30 PM

End Date

2-3-2018 1:45 PM

Abstract

It was long assumed that the oxytocin ligand was conserved across all mammalian species, but recent studies have shown that a clade of New World monkeys (NWM) exhibits considerable diversity in both oxytocin ligand (OT) and receptor (OTR) structure. Most notable is the variant Pro8-OT, with proline instead of leucine at the eighth position. Genetic variability is associated with social behavior: species that express Pro8-OT also often engage in biparental care and social monogamy. When marmosets, a biparental and monogamous Pro8-OT NWM species, are administered the ancestral Leu8-OT, there is no change in social behavior compared to saline. However, when Pro8-OT is administered, marmosets engage in fewer socio-sexual and prosocial behaviors with an opposite-sex “stranger,” indicating strong fidelity to the individual’s long-term pair-mate. We tested the hypothesis that genetic differences in oxytocin ligands were related to the receptor binding affinities and signaling potencies at the OTRs from four primate species, all expressed in the same cell background, and each representing a unique combination of ancestral lineage, breeding system, and native OT ligand: human (Leu8-OT, monogamous, apes), macaque (Leu8-OT, nonmonogamous, Old World monkey), marmoset (Pro8-OT, monogamous, NWM) and Titi monkey (Leu8-OT, monogamous, NWM). Pro8-OT bound with 2-fold greater affinity than Leu8-OT at the human and marmoset OTRs, and Pro8-OT was more potent and Leu8-OT at the marmoset OTR. Thus, the co-evolution of OT and the OTR results in functional changes at the ligand-receptor interface.

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Mar 2nd, 12:30 PM Mar 2nd, 1:45 PM

Functional characteristics of four primate oxytocin receptors: relationships to biparental care and social monogamy

Dr. C.C. and Mabel L. Criss Library

It was long assumed that the oxytocin ligand was conserved across all mammalian species, but recent studies have shown that a clade of New World monkeys (NWM) exhibits considerable diversity in both oxytocin ligand (OT) and receptor (OTR) structure. Most notable is the variant Pro8-OT, with proline instead of leucine at the eighth position. Genetic variability is associated with social behavior: species that express Pro8-OT also often engage in biparental care and social monogamy. When marmosets, a biparental and monogamous Pro8-OT NWM species, are administered the ancestral Leu8-OT, there is no change in social behavior compared to saline. However, when Pro8-OT is administered, marmosets engage in fewer socio-sexual and prosocial behaviors with an opposite-sex “stranger,” indicating strong fidelity to the individual’s long-term pair-mate. We tested the hypothesis that genetic differences in oxytocin ligands were related to the receptor binding affinities and signaling potencies at the OTRs from four primate species, all expressed in the same cell background, and each representing a unique combination of ancestral lineage, breeding system, and native OT ligand: human (Leu8-OT, monogamous, apes), macaque (Leu8-OT, nonmonogamous, Old World monkey), marmoset (Pro8-OT, monogamous, NWM) and Titi monkey (Leu8-OT, monogamous, NWM). Pro8-OT bound with 2-fold greater affinity than Leu8-OT at the human and marmoset OTRs, and Pro8-OT was more potent and Leu8-OT at the marmoset OTR. Thus, the co-evolution of OT and the OTR results in functional changes at the ligand-receptor interface.