Molecular evolution of the neurohypophysial hormone precursors in mammals: Comparative genomics reveals novel mammalian oxytocin and vasopressin analogues

Wallis, Michael

doi:10.1016/j.ygcen.2012.07.030

Cited by 40 publications

(38 citation statements)

References 37 publications

(55 reference statements)

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“…OXT differs from its paralog vasopressin (AVP; Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly) at positions 3 and 8. Variation at position 8 also identifies nonplacental OXT/AVP-like nonapeptides, such as mesotocin, present in some marsupials (7,9). These findings dispel the notion of a universal OXT amino acid sequence for placental mammals.…”

mentioning

confidence: 75%

Evolutionary pattern in the OXT-OXTR system in primates: Coevolution and positive selection footprints

Vargas-Pinilla

Paixão‐Côrtes

Paré

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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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.OXT | OXTR | primates | coevolution | behavior

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mentioning

confidence: 75%

Evolutionary pattern in the OXT-OXTR system in primates: Coevolution and positive selection footprints

Vargas-Pinilla

Paixão‐Côrtes

Paré

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Central Oxytocin Pathways receptors progressively acquired the molecular features of the V1a, V1b, and V2 AVP receptors, while the mesotocin receptor evolved into the mammalian OTR (20,21). OT and OTR are not conserved in all mammals; in particular, variation in the OT peptide have been reported in marsupials (21) and in New World monkeys, which emerged approximately 30 million years ago and are now present in South and Central America (22,23).…”

Section: Ot Receptor Trajectories In Evolutionmentioning

confidence: 99%

“…OT and OTR are not conserved in all mammals; in particular, variation in the OT peptide have been reported in marsupials (21) and in New World monkeys, which emerged approximately 30 million years ago and are now present in South and Central America (22,23). Some OT variations in New World monkeys may be related to ecological and social behavior traits, such as paternal behavior (23).…”

Section: Ot Receptor Trajectories In Evolutionmentioning

confidence: 99%

Assembling the Puzzle: Pathways of Oxytocin Signaling in the Brain

Grinevich

Knobloch‐Bollmann

Eliava

et al. 2016

Biological Psychiatry

238

174

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Oxytocin (OT) is a neuropeptide, which can be seen to be one of the molecules of the decade due to its profound prosocial effects in nonvertebrate and vertebrate species, including humans. Although OT can be detected in various physiological fluids (blood, saliva, urine, cerebrospinal fluid) and brain tissue, it is unclear whether peripheral and central OT releases match and synergize. Moreover, the pathways of OT delivery to brain regions involved in specific behaviors are far from clear. Here, we discuss the evolutionarily and ontogenetically determined pathways of OT delivery and OT signaling, which orchestrate activity of the mesolimbic social decision-making network. Furthermore, we speculate that both the alteration in OT delivery and OT receptor expression may cause behavioral abnormalities in patients afflicted with psychosocial diseases.

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“…OT and AVP are also structurally very similar, differing by only two amino acids in most mammals (Wallis, 2012). Given this high degree of conservation in both receptors and peptides, the development of selective agonists and antagonists has proved to be a daunting task .…”

Section: Introductionmentioning

confidence: 99%

Selective and Potent Agonists and Antagonists for Investigating the Role of Mouse Oxytocin Receptors

Busnelli

Bulgheroni

Manning

et al. 2013

J Pharmacol Exp Ther

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The neuropeptides oxytocin (OT) and vasopressin (AVP) have been shown to play a central role in social behaviors; as a consequence, they have been recognized as potential drugs to treat neurodevelopmental and psychiatric disorders characterized by impaired social interactions. However, despite the basic and preclinical relevance of mouse strains carrying genetic alterations in the OT/AVP systems to basic and preclinical translational neuroscience, the pharmacological profile of mouse OT/AVP receptor subtypes has not been fully characterized. To fill in this gap, we have characterized a number of OT and AVP agonists and antagonists at three murine OT/AVP receptors expressed in the nervous system as follows: the oxytocin (mOTR) and vasopressin V1a (mV1aR) and V1b (mV1bR) subtypes. These three receptors were transiently expressed in vitro for binding and intracellular signaling assays, and then a homology model of the mOTR structure was constructed to investigate how its molecular features compare with human and rat OTR orthologs. Our data indicate that the selectivity profile of the natural ligands, OT and AVP, is conserved in humans, rats, and mice. Furthermore, we found that the synthetic peptide [Thr 4 Gly 7 ]OT (TGOT) is remarkably selective for the mOTR and, like the endogenous OT ligand, activates G q and G i and recruits b-arrestins. Finally, we report three antagonists that exhibit remarkably high affinities and selectivities at mOTRs. These highly selective pharmacological tools will contribute to the investigation of the specific physiologic and pathologic roles of mOTR for the development of selective OT-based therapeutics.

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Molecular evolution of the neurohypophysial hormone precursors in mammals: Comparative genomics reveals novel mammalian oxytocin and vasopressin analogues

Cited by 40 publications

References 37 publications

Evolutionary pattern in the OXT-OXTR system in primates: Coevolution and positive selection footprints

Evolutionary pattern in the OXT-OXTR system in primates: Coevolution and positive selection footprints

Assembling the Puzzle: Pathways of Oxytocin Signaling in the Brain

Selective and Potent Agonists and Antagonists for Investigating the Role of Mouse Oxytocin Receptors

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