Oxytocin receptor gene sequences in owl monkeys and other primates show remarkable interspecific regulatory and protein coding variation

Abstract

The oxytocin (OT) hormone pathway is involved in numerous physiological processes, and one of its receptor genes (OXTR) has been implicated in pair bonding behavior in mammalian lineages. This observation is important for understanding social monogamy in primates, which occurs in only a small subset of taxa, including Azara's owl monkey (Aotus azarae). To examine the potential relationship between social monogamy and OXTR variation, we sequenced its 5' regulatory (4936bp) and coding (1167bp) regions in 25 owl monkeys from the Argentinean Gran Chaco, and examined OXTR sequences from 1092 humans from the 1000 Genomes Project. We also assessed interspecific variation of OXTR in 25 primate and rodent species that represent a set of phylogenetically and behaviorally disparate taxa. Our analysis revealed substantial variation in the putative 5' regulatory region of OXTR, with marked structural differences across primate taxa, particularly for humans and chimpanzees, which exhibited unique patterns of large motifs of dinucleotide A+T repeats upstream of the OXTR 5' UTR. In addition, we observed a large number of amino acid substitutions in the OXTR CDS region among New World primate taxa that distinguish them from Old World primates. Furthermore, primate taxa traditionally defined as socially monogamous (e.g., gibbons, owl monkeys, titi monkeys, and saki monkeys) all exhibited different amino acid motifs for their respective OXTR protein coding sequences. These findings support the notion that monogamy has evolved independently in Old World and New World primates, and that it has done so through different molecular mechanisms, not exclusively through the oxytocin pathway.

Evolving the neuroendocrine physiology of human and primate cooperation and collective action

“…Furthermore, bonobos and chimpanzees do not exhibit these candidate SNPs despite differences in social behaviour [143], and variation in OXTR as well as prolactin and vasopressin receptor genes across primates more broadly do not easily map onto social and mating systems [148,149,155]. Finally, suggestive results have been found for various other receptor genes, as summarized in table 3.…”

“…Phylogenetic analyses of more than 100 avian species suggest that environmental constraints shape reproductive behaviour and mediate both baseline and peak levels of androgens [157]. However, phylogenetic analyses examining differences in vasopressin receptor vasopressin receptor AVPR1A-RS3 carriers less fair in dictator games [140,141] double deletion of DupB region (which includes RS3) decreases social cognition, competence chimpanzees [142] no deletion in bonobos [143] vasopressin receptor AVPR1A-RS3 more likely to divorce [144] OT receptor OXTR SNPs (rs53576 and rs2254298) increase prosociality no variation in chimpanzees and bonobos [143] mixed results [145,146], but some meta-analyses show no significant effect [147] OXTR and pair-bonding receptor differences in primates do not map onto mating system [148] prolactin receptor pair-bonding receptor differences do not map onto paternal care [149] rstb.royalsocietypublishing.org Phil. Trans.…”

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.…”

Neuropeptide diversity and the regulation of social behavior in New World primates

“…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). Another independent survey of the OTR variability in primates demonstrated important differences in amino acid motifs in OT coding regions across socially monogamous primates (e.g., humans, gibbons, owl monkeys, titi monkeys, saki monkeys; Babb et al, 2015). This finding suggests that monogamy has evolved independently in Great Apes and NWMs by potentially different molecular mechanisms (Babb et al, 2015).…”

“…Another independent survey of the OTR variability in primates demonstrated important differences in amino acid motifs in OT coding regions across socially monogamous primates (e.g., humans, gibbons, owl monkeys, titi monkeys, saki monkeys; Babb et al, 2015). This finding suggests that monogamy has evolved independently in Great Apes and NWMs by potentially different molecular mechanisms (Babb et al, 2015). 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).…”