Signatures of positive selection in the cis-regulatory sequences of the human oxytocin receptor (OXTR) and arginine vasopressin receptor 1a (AVPR1A) genes

Author(s)
Helmut Schaschl, Susanne Huber, Katrin Schäfer, Sonja Windhager, Bernard Wallner, Martin Fieder
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.

Organisation(s)
Department of Evolutionary Anthropology
Journal
BMC Evolutionary Biology
Volume
15
No. of pages
12
ISSN
1471-2148
DOI
https://doi.org/10.1186/s12862-015-0372-7
Publication date
05-2015
Peer reviewed
Yes
Austrian Fields of Science 2012
301301 Human genetics, 106036 Population genetics
Keywords
Portal url
https://ucris.univie.ac.at/portal/en/publications/signatures-of-positive-selection-in-the-cisregulatory-sequences-of-the-human-oxytocin-receptor-oxtr-and-arginine-vasopressin-receptor-1a-avpr1a-genes(ff2ddac5-b193-4ce3-95fa-b41044946809).html