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Open Access Research article

A complex selection signature at the human AVPR1B gene

Rachele Cagliani1, Matteo Fumagalli12, Uberto Pozzoli1, Stefania Riva1, Matteo Cereda1, Giacomo P Comi3, Linda Pattini2, Nereo Bresolin13 and Manuela Sironi1*

Author Affiliations

1 Scientific Institute IRCCS E. Medea, Bioinformatic Lab, Via don L. Monza 20, 23842 Bosisio Parini (LC), Italy

2 Bioengineering Department, Politecnico di Milano, P.zza L. da Vinci, 32, 20133 Milan, Italy

3 Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena Foundation, Via F. Sforza 35, 20100 Milan, Italy

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BMC Evolutionary Biology 2009, 9:123  doi:10.1186/1471-2148-9-123

Published: 1 June 2009

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.

Conclusion

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.