Oxytocin and vasotocin receptor variation sheds light into the evolution of human prosociality

Modern human lifestyle strongly depends on complex social traits like empathy, tolerance and cooperation. These diverse facets of social cognition have been associated with variation in the oxytocin receptor (OTR) and its sister genes, the vasotocin/vasopressin receptors (VTR1A/AVPR1A and AVPR1B/VTR1B). Here, we compared the full genomic sequences of these receptors between modern humans, archaic humans, and 12 non-human primate species, and identified sites that show heterozygous variation in modern humans and archaic humans distinct from variation in other primates, and that have associated literature. We performed variant clustering, pathogenicity prediction, regulation, linkage disequilibrium frequency and selection analyses on data in different modern-human populations. We found five sites with modern human specific variation, where the modern human allele is the major allele in the global population (OTR: rs1042778, rs237885, rs6770632; VTR1A: rs10877969; VTR1B: rs33985287). Among them, the OTR-rs6770632 was predicted to be the most functional. We found two sites where alleles (OTR: rs59190448 and rs237888)1 present only in modern humans and archaic humans are under positive selection in modern humans, with rs237888 predicted to be a highly functional site. We identified three sites of convergent evolution between modern humans and bonobos (OTR: rs2228485 and rs237897; VTR1A: rs1042615), with OTR-rs2228485 ranking very highly in terms of functionality and being under balancing selection in modern humans. Our findings shed light on evolutionary questions of modern human and hominid prosociality, as well as on similarities in the social behavior between modern humans and bonobos.