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.
Highlights
Oxytocin (OXT) is a cyclic nonapeptide hormone synthesized primarily by neurons in hypothalamic nuclei
We identified five distinct OXT ligands in New World monkeys (NWM)
At least one genus in all three NWM clades possessed non-consensus mammalian OXT; OXT ligand variation is widespread in NWM
Summary
Oxytocin (OXT) is a cyclic nonapeptide hormone synthesized primarily by neurons in hypothalamic nuclei. OXT is involved in the regulation of multiple facets of social relationships in mammals, including social monogamy [5,6,7]. A novel OXT variant was identified in four species of New World monkeys (NWM), involving a substitution from leucine to proline at position eight (Pro8-OXT) [9]. It is currently unknown whether novel OXT variants are present throughout NWM (Platyrrhini), which consists of 17 genera distributed across Cebidae, Atelidae, and Pitheciidae clades. Given the relatively high percentage of NWM species exhibiting social monogamy (more than 50%) relative to other primate or mammalian clades [10], we statistically evaluated the association between OXT/OXTR variants and social monogamy
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