10Modern humans' lifestyle strongly depends on complex social skills like empathy, tolerance and cooperation. Variation in the oxytocin receptor (OXTR) and the arginine-vasopressin receptors (AVPR1A, AVPR1B genes) has been widely associated with diverse facets of social cognition, but the extent to which these variants may have contributed to the evolution of human prosociality remains to be elucidated. In this study, we compared the OXTR, AVPR1A and AVPR1B DNA sequences of modern humans to those of our closest extinct and extant relatives, and then clustered the variants we identified based on their distribution in the species studied. This clustering, along with the functional importance retrieved for each variant and their frequency in different modern-human populations, is then used to determine if any of the OXTR, AVPR1A and AVPR1B-variants might have had an impact at different evolutionary stages. We report a total of 29 SNPs, associated with phenotypic effects ranging from clearly pro-social to mixed or antisocial. Regarding modern human-specific alleles that could correlate with a shift towards prosociality in modern-humans, we highlight one allele in AVPR1A (rs11174811), found at high frequency and linked to prosocial phenotypes in modern humans, while the ancestral allele is associated with antisocial phenotypes. We also report three sites of putatively convergent changes between modern humans and bonobos (rs237897(A), rs2228485(G) and rs1042615(A)), and note the absence of such a convergent pattern between modern humans and chimpanzees. Finally, we observe the high concentration of 'modern human specific' alleles in vasopressin receptors not paralleled in the oxytocin receptor. 11 1 Introduction 12 Oxytocin (OXT) and vasopressin (AVP) are important neurotransmitters that function through their respective receptors to 13 regulate a diverse set of biological processes, such as pregnancy and uterine contractions, milk-ejection, copulation and orgasm, 14 attachment between mothers and their young, bond formation, suppression of stress, thermoregulation, olfactory processing, 15 eye-contact and recognition of familiar individuals 1 . OXT and AVP are closely related structurally and evolutionarily: they 16 have been argued to be the product of a local duplication event that took place before the origin of vertebrates 2 , and they only 17 differ in two (of the nine) amino acids, although they display differences at a functional level 1 . Each binds to their respective 18 receptor(s) (OXTR in the case of oxytocin, and AVPR1A, AVPR1B, and AVPR2 in the case of vasopressin), but their molecular 19 similarities allow for crosstalk in the brain and peripheral organs 3 .
20Variation in the genes that code for OXT and AVP receptors (OXTR and mainly AVPR1A and AVPR1B) have long been 21 associated with different social behaviors 4 . Single Nucleotide Polymorphisms (SNPs) in these genes in modern humans have 22 been claimed to be implicated in altruism, face recognition, stress levels and empathy, but also in socioco...