Evolutionary pattern in the OXT-OXTR system in primates: Coevolution and positive selection footprints
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Significance: It was previously believed that placental mammals present no variability in oxytocin (OXT). The present study reports novel data on the diversity of OXT and its receptor ( OXTR ) in primate species, including New World monkeys. Contrary to prior expectations, we found three novel OXT forms and several OXTR nonsynonymous changes not previously described. In the Cebidae family, signals of positive selection were found for an OXT variant at position 8, which is associated with larger litter sizes. We detected positive selection for OXTR forms and report a coevolutionary process between changes in OXT and OXTR.
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New World monkeys have genetic variation in OT and AVP peptide and receptor genes across species.
“Species differences in receptor binding characteristics vary widely, especially in light of recent discoveries in New World monkeys, which show genetic variations in both the OT and AVP peptide and receptor genes across species (105-110).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [107]
Receptor binding characteristics differ widely across species.
“Species differences in receptor binding characteristics vary widely, especially in light of recent discoveries in New World monkeys, which show genetic variations in both the OT and AVP peptide and receptor genes across species (105-110).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [107]
Recent discoveries have identified surprising variability in OT and peptide structure in New World monkeys (NWM), with five new OT variants identified to date.
“recent discoveries have identified surprising variability in OT and peptide structure in New World monkeys (NWM), with five new OT variants identified to date”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
The prevalence of nonsynonymous substitutions in OXT in every genus of New World monkeys codes for five distinct forms of OT in addition to consensus mammalian Leu8-OT, for a total of six OT ligand variants in this taxon.
“The feature that stands out most prominently is the prevalence of NSs in OXT in every genus of NWM, which in turn code for five distinct forms of OT in addition to consensus mammalian Leu8-OT, for a total of six OT ligand variants in this taxon.”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
Some species of Saguinus possess a second nonsynonymous substitution at the 3rd position (ATC to GTC), producing a residue substitution of isoleucine to valine, yielding Val3-Pro8-OT.
“some species of Saguinus also possess at second NS at the 3rd position (ATC → GTC), producing a residue substitution of isoleucine → valine, yielding Val3-Pro8-OT.”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
Within New World monkeys, OTR sequence phylogenies significantly group by OT variants, social monogamy, and paternal care.
“examining OTR sequence phylogeny within the NWMs demonstrates OTR sequence phylogenies also significantly group by OT variants, social monogamy (Ren et al., 2015), and paternal care (Vargas-Pinilla et al., 2015).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
OTR variability among primates and especially New World monkeys has been significantly associated with social monogamy and paternal care in New World monkeys.
“OTR variability among primates and especially NWM has been significantly associated with the occurrence of two important social phenotypes in NWM: social monogamy (Ren et al., 2015) and paternal care in (Vargas-Pinilla et al., 2015).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
The association between OTR variability and sociality suggests that these systems are involved, at least in part, in the evolution and maintenance of these social phenotypes in New World monkeys.
“Overall, the association between OTR variability and sociality suggest that, at least in part, these systems are involved in the evolution and maintenance of these social phenotypes in NWM (Ren et al., 2015; Vargas-Pinilla et al., 2015).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
Saimiri, a Pro8-OT species, has a substitution at F103Y, a key residue of the putative binding pocket of OTR.
“One important exception is in Saimiri. This Pro8-OT species has a substitution at F103Y, which is a key residue of the putative binding pocket of OTR (Gimpl and Fahrenholz, 2001; Vargas-Pinilla et al., 2015).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
Most residues critical for receptor binding or function are conserved in the OTR of New World monkey species.
“Most of the residues that have been shown or are predicted to be critical for receptor binding or function (reviewed in Gimpl and Fahrenholz, 2001; Koehbach et al., 2013) are conserved in the OTR of NWM species (Ren et al., 2015; Vargas-Pinilla et al., 2015).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
The F103Y residue is homologous to Tyr115 in V1aR, which is critical for AVP binding and may confer increased binding affinity for AVP to Saimiri OTR.
“Vargas-Pinilla et al. (2015) identified this residue as homologous to Tyr115 in V1aR, which is critical for AVP binding and may confer increased binding affinity for AVP to Saimiri OTR (Chini et al., 1995).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
This residue may exhibit intraspecific polymorphism because one S. sciureus receptor sequence shows Phe115 and one shows Tyr115.
“This residue may also exhibit intraspecific polymorphism because one of the receptor sequences available for S. sciureus shows Phe115, and one shows Tyr115 (Lee et al., 2011; Ren et al., 2015; Vargas-Pinilla et al., 2015).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
A new phosphorylation site in OTR of Callithrix at R149S and shortening of a Ser cluster in OTR of Saguinus important for beta-arrestin mediated desensitization and receptor recycling were identified.
“Additionally, (Vargas-Pinilla et al., 2015) identified a new phosphorylation site in the OTR of Callithrix at R149S, and the shortening of a Ser cluster in the OTR of Saguinus that is important for β-arrestin mediated desensitization and receptor recycling (Innamorati et al., 1998; Oakley et al., 2001; Vargas-Pinilla et al., 2015).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
OT ligand variation is statistically associated with paternal care across NWM genera.
“While OT ligand variation has been statistically associated with the presence of social monogamy (Ren et al., 2015) and paternal care (Vargas-Pinilla et al., 2015) across NWM genera”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Vargas-Pinilla et al., 2015
These varied OXT/OXTR systems potentially coevolved to modulate species-specific social behaviour such as social monogamy and paternal care.
“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).”
From Inequity aversion strategies between marmosets are influenced by partner familiarity and sex but not by oxytocin (2016) · cites this paper as Vargas-Pinilla et al., 2015
The proline substitution results in a substantially altered structure in the "linear" portion of the molecule that likely affects OXT ligand-OXTR binding, and subsequently behavior.
“Due to a proline substitution at the 8th amino-acid position, the marmoset variant of OXT (Pro8-OXT) is distinctly different than the consensus mammalian variant of OXT (Leu8-OXT), and results in a substantially altered structure in the “linear” portion of the molecule that likely affects OXT ligand-OXTR binding, and subsequently behavior.”
From Marmosets treated with oxytocin are more socially attractive to their long-term mate (2015) · cites this paper as Vargas-Pinilla et al., 2015
Due to a proline substitution at the 8th amino-acid position, the marmoset variant of OXT (Pro8-OXT) is distinctly different than the consensus mammalian variant of OXT (Leu8-OXT).
“Due to a proline substitution at the 8th amino-acid position, the marmoset variant of OXT (Pro8-OXT) is distinctly different than the consensus mammalian variant of OXT (Leu8-OXT), and results in a substantially altered structure in the “linear” portion of the molecule that likely affects OXT ligand-OXTR binding, and subsequently behavior.”
From Marmosets treated with oxytocin are more socially attractive to their long-term mate (2015) · cites this paper as Vargas-Pinilla et al., 2015
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- Authors
- Vargas-Pinilla, P., Paixão-Côrtes, V. R., Paré, P., Tovo-Rodrigues, L., Vieira, C. M. D. A. G., Xavier, A., Comas, D., Pissinatti, A., Sinigaglia, M., Rigo, M. M., Vieira, G. F., Lucion, A. B., Salzano, F. M., & Bortolini, M. C.
- Affiliations
- Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre, RS, Brazil;
- Universidade Federal do Rio Grande do Sul (BR)
- Universitat Pompeu Fabra (ES)
- Centro de Primatologia do Rio de Janeiro, 20940-200 Rio de Janeiro, RJ, Brazil; and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-12-22
- Volume
- 112
- Issue
- 1
- Pages
- 88-93
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4291646
- OpenAlex
- W2021978125
- Cited by
- 59
- References
- 66
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2021: 3 · 2020: 7 · 2019: 5 · 2018: 11 · 2017: 7 · 2016: 10 · 2015: 10
- FWCI
- 13.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Social Sciences › Psychology › Social Psychology › Primate Behavior and Ecology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, oxytocin receptor, primate evolution, positive selection, coevolution, New World monkeys, Cebidae, litter size, phosphorylation sites, receptor desensitization, male parental care, placental mammals
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Male, Molecular Sequence Data, Oxytocin, Primates, Selection, Genetic, Receptors, Oxytocin, Evolution, Molecular
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