Genetic Diversity in Oxytocin Ligands and Receptors in New World Monkeys

Abstract

Oxytocin (OXT) is an important neurohypophyseal hormone that influences wide spectrum of reproductive and social processes. Eutherian mammals possess a highly conserved sequence of OXT (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly). However, in this study, we sequenced the coding region for OXT in 22 species covering all New World monkeys (NWM) genera and clades, and characterize five OXT variants, including consensus mammalian Leu8-OXT, major variant Pro8-OXT, and three previously unreported variants: Ala8-OXT, Thr8-OXT, and Phe2-OXT. Pro8-OXT shows clear structural and physicochemical differences from Leu8-OXT. We report multiple predicted amino acid substitutions in the G protein-coupled OXT receptor (OXTR), especially in the critical N-terminus, which is crucial for OXT recognition and binding. Genera with same Pro8-OXT tend to cluster together on a phylogenetic tree based on OXTR sequence, and we demonstrate significant coevolution between OXT and OXTR. NWM species are characterized by high incidence of social monogamy, and we document an association between OXTR phylogeny and social monogamy. Our results demonstrate remarkable genetic diversity in the NWM OXT/OXTR system, which can provide a foundation for molecular, pharmacological, and behavioral studies of the role of OXT signaling in regulating complex social phenotypes.

Inequity aversion strategies between marmosets are influenced by partner familiarity and sex but not by oxytocin

“…First, marmosets are cooperatively-breeding NHPs, and in contrast to many other primates, marmosets are highly prosocial and form long-term male-female cooperative relationships (Agmo, Smith, Birnie, & French, 2012; Burkart, Fehr, Efferson, & van Schaik, 2007; Evans, 1983; Schaffner, Shepherd, Santos, & French, 1995). Second, New World monkeys (NWMs), including callitrichids, possess notably remarkable interspecific OXT and OXT receptor (OXTR) diversity relative to other mammals (Babb, Fernandez-Duque, & Schurr, 2015; Lee et al, 2011; Ren et al, 2015; Vargas-Pinilla et al, 2015; Wallis, 2012), and these varied OXT/OXTR systems potentially coevolved to modulate species-specific social behaviour such as social monogamy and paternal care (Ren et al, 2015; Vargas-Pinilla et al, 2015). Specifically, marmosets possess a modified OXT ligand with a leucine to proline (Pro 8 -OXT) substitution at the eighth amino acid position resulting in a significant change in the structure of the OXT ligand.…”

Initial investigation of three selective and potent small molecule oxytocin receptor PET ligands in New World monkeys

“…Therefore, utilizing 3 in behavioral studies to block endogenous OXTR signaling may not be optimal for investigating specific behavioral responses focused on the OXTR because of the possibility of its antagonistic effects on AVPR1a signaling. It should be noted here that species differences are also present in the structure of the OXTR, as well as the oxytocin peptide [41]. Specifically, the amino acid sequence of oxytocin in the marmoset differs from that of the human and titi monkey oxytocin by one amino acid (a proline is substituted for a leucine in the 8th position of the nonapeptide) [41].…”

“…It should be noted here that species differences are also present in the structure of the OXTR, as well as the oxytocin peptide [41]. Specifically, the amino acid sequence of oxytocin in the marmoset differs from that of the human and titi monkey oxytocin by one amino acid (a proline is substituted for a leucine in the 8th position of the nonapeptide) [41]. Additionally, in comparison to the human receptor, the OXTR of the marmoset differs by eight amino acids of the 38 amino acid sequence of the N-terminus extracellular tail which is purported to interact with oxytocin [41].…”

“…Specifically, the amino acid sequence of oxytocin in the marmoset differs from that of the human and titi monkey oxytocin by one amino acid (a proline is substituted for a leucine in the 8th position of the nonapeptide) [41]. Additionally, in comparison to the human receptor, the OXTR of the marmoset differs by eight amino acids of the 38 amino acid sequence of the N-terminus extracellular tail which is purported to interact with oxytocin [41]. These molecules would therefore need to be assayed for binding to marmoset OXTR in order to be confident in their potency and functionality.…”

“…These molecules would therefore need to be assayed for binding to marmoset OXTR in order to be confident in their potency and functionality. Conversely, the oxytocin peptide sequence in titi monkeys is identical to that of humans, and their OXTR only differs in three amino acid positions of the 38 amino acids in the extracellular sequence [41]. …”