title: A complex selection signature at the human AVPR1B gene.
abstract: BACKGROUND
  The vasopressin receptor type 1b (AVPR1B) is mainly expressed by pituitary corticotropes and it mediates the stimulatory effects of AVP on ACTH release; common AVPR1B haplotypes have been involved in mood and anxiety disorders in humans, while rodents lacking a functional receptor gene display behavioral defects and altered stress responses.
  
  
  RESULTS
  Here we have analyzed the two exons of the gene and the data we present suggest that AVPR1B has been subjected to natural selection in humans. In particular, analysis of exon 2 strongly suggests the action of balancing selection in African populations and Europeans: the region displays high nucleotide diversity, an excess of intermediate-frequency alleles, a higher level of within-species diversity compared to interspecific divergence and a genealogy with common haplotypes separated by deep branches. This relatively unambiguous situation coexists with unusual features across exon 1, raising the possibility that a nonsynonymous variant (Gly191Arg) in this region has been subjected to directional selection.
  
  
  CONCLUSIONS
  Although the underlying selective pressure(s) remains to be identified, we consider this to be among the first documented examples of a gene involved in mood disorders and subjected to natural selection in humans; this observation might add support to the long-debated idea that depression/low mood might have played an adaptive role during human evolution.
authors.affiliation: Scientific Institute IRCCS E, Medea, Bioinformatic Lab, Bosisio Parini, LC, Italy. rachele.cagliani@bp.lnf.it
authors.forename: Rachele
authors.initials: R
authors.lastname: Cagliani
authors.forename: Matteo
authors.initials: M
authors.lastname: Fumagalli
authors.forename: Uberto
authors.initials: U
authors.lastname: Pozzoli
authors.forename: Stefania
authors.initials: S
authors.lastname: Riva
authors.forename: Matteo
authors.initials: M
authors.lastname: Cereda
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Linda
authors.initials: L
authors.lastname: Pattini
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Manuela
authors.initials: M
authors.lastname: Sironi
mesh_terms: D000818:Animals; D044383:Black People / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D014644:Genetic Variation; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D019964:Mood Disorders / Q000235:genetics; D010802:Phylogeny; D017483:Receptors, Vasopressin / Q000235:genetics*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
chemical_list: D017483:Receptors, Vasopressin