title: Signatures of positive selection in the cis-regulatory sequences of the human oxytocin receptor (OXTR) and arginine vasopressin receptor 1a (AVPR1A) genes.
abstract: BACKGROUND
  The evolutionary highly conserved neurohypophyseal hormones oxytocin and arginine vasopressin play key roles in regulating social cognition and behaviours. The effects of these two peptides are meditated by their specific receptors, which are encoded by the oxytocin receptor (OXTR) and arginine vasopressin receptor 1a genes (AVPR1A), respectively. In several species, polymorphisms in these genes have been linked to various behavioural traits. Little, however, is known about whether positive selection acts on sequence variants in genes influencing variation in human behaviours.
  
  
  RESULTS
  We identified, in both neuroreceptor genes, signatures of balancing selection in the cis-regulative acting sequences such as transcription factor binding and enhancer sequences, as well as in a transcriptional repressor sequence motif. Additionally, in the intron 3 of the OXTR gene, the SNP rs59190448 appears to be under positive directional selection. For rs59190448, only one phenotypical association is known so far, but it is in high LD' (>0.8) with loci of known association; i.e., variants associated with key pro-social behaviours and mental disorders in humans.
  
  
  CONCLUSIONS
  Only for one SNP on the OXTR gene (rs59190448) was a sign of positive directional selection detected with all three methods of selection detection. For rs59190448, however, only one phenotypical association is known, but rs59190448 is in high LD' (>0.8), with variants associated with important pro-social behaviours and mental disorders in humans. We also detected various signatures of balancing selection on both neuroreceptor genes.
authors.affiliation: Department of Anthropology, University of Vienna, Vienna, Austria. helmut.schaschl@univie.ac.at.
authors.forename: Helmut
authors.initials: H
authors.lastname: Schaschl
authors.affiliation: Department of Anthropology, University of Vienna, Vienna, Austria. susanne.huber@univie.ac.at.
authors.forename: Susanne
authors.initials: S
authors.lastname: Huber
authors.affiliation: Department of Anthropology, University of Vienna, Vienna, Austria. katrin.schaefer@univie.ac.at.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schaefer
authors.affiliation: Department of Anthropology, University of Vienna, Vienna, Austria. sonja.windhager@univie.ac.at.
authors.forename: Sonja
authors.initials: S
authors.lastname: Windhager
authors.affiliation: Department of Anthropology, University of Vienna, Vienna, Austria. bernard.wallner@univie.ac.at.|Cognitive Science Platform at the University of Vienna, Vienna, Austria. bernard.wallner@univie.ac.at.|Department of Behavioural Biology, University of Vienna, Vienna, Austria. bernard.wallner@univie.ac.at.
authors.forename: Bernard
authors.initials: B
authors.lastname: Wallner
authors.affiliation: Department of Anthropology, University of Vienna, Vienna, Austria. martin.fieder@univie.ac.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Fieder
mesh_terms: D019143:Evolution, Molecular; D005828:Genetics, Population; D063426:Human Migration; D006801:Humans; D010121:Oxytocin / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018045:Receptors, Oxytocin / Q000235:genetics*; D017483:Receptors, Vasopressin / Q000235:genetics*; D012919:Social Behavior
chemical_list: C000599871:AVPR1A protein, human; C569600:OXTR protein, human; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D010121:Oxytocin