Signatures of positive selection in the cis-regulatory sequences of the human oxytocin receptor (OXTR) and arginine vasopressin receptor 1a (AVPR1A) genes (original) (raw)
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The contributions of oxytocin and vasopressin pathway genes to human behavior HORMONES & BEHAVIOR
Arginine vasopressin (AVP) and oxytocin (OXT) are social hormones and mediate affiliative behaviors in mammals and as recently demonstrated, also in humans. There is intense interest in how these simple nonapeptides mediate normal and abnormal behavior, especially regarding disorders of the social brain such as autism that are characterized by deficits in social communication and social skills. The current review examines in detail the behavioral genetics of the first level of human AVP-OXT pathway genes including arginine vasopressin 1a receptor (AVPR1a), oxytocin receptor (OXTR), AVP (AVP-neurophysin II [NPII]) and OXT (OXT neurophysin I [NPI]), oxytocinase/vasopressinase (LNPEP), ADPribosyl cyclase (C D38) and arginine vasopressin 1b receptor (AVPR1b). Wherever possible we discuss evidence from a variety of research tracks including molecular genetics, imaging genomics, pharmacology and endocrinology that support the conclusions drawn from association studies of social phenotypes and detail how common polymorphisms in AVP-OXT pathway genes contribute to the behavioral hard wiring that enables individual Homo sapiens to interact successfully with conspecifics. K eywords Oxytocin, vasopressin, ADP-ribosyl cyclase (CD38), oxytocin receptor (OXTR), arginine vasopressin 1a receptor (AVPR1a), arginine receptor 1b receptor (AVPR1b), LNPEP (oxytocinase), plasma oxytocin, neurophysin, polymorphism
Expression of the Oxytocin and Vasopressin Genes
Journal of Neuroendocrinology, 1992
Rat (49) Mouse (281 Human (29) Cow (24) Consensus Rat Mouse Human cow Consensus Rat Mouse Human cow Consensus Rat Mouse Human cow Consensus Rat Mouse Human cow Consensus AAAGCTCA-C CTGGTAT-C GATGCTTCCT CTTATCCTAC ACCACAACTA ACAAACCTG-CCC-CACCTC CT-GGT CCTGACCCTG CTGCAGACCT AAAGCCCA-C CTGATAT-G GGTGCTTCCT CTCATCCTAT ACCACAACTA ACAA-CCTG-CCCACCCCTT CT-GGT GCTGACCCTG CTCCATACGT GACCCTTATC TTGTTGTCAC AGGGCTAACC CTCCCCACAC ACC-TGGCTG TC-CCCTGC CCCACAGCTC CTAGCCAGGG CCTGTCCCTG CCCCTAACAC
Genetics and Molecular Biology, 2016
Oxytocin receptor (OXTR) and arginine vasopressin receptors (AVPR1a, AVPR1b, and AVPR2) are paralogous genes that emerged through duplication events; along the evolutionary timeline, owing to speciation, numerous orthologues emerged as well. In order to elucidate the evolutionary forces that shaped these four genes in placental mammals and to reveal specific aspects of their protein structures, 35 species were selected. Specifically, we investigated their molecular evolutionary history and intrinsic protein disorder content, and identified the presence of short linear interaction motifs. OXTR seems to be under evolutionary constraint in placental mammals, whereas AVPR1a, AVPR1b, and AVPR2 exhibit higher evolutionary rates, suggesting that they have been under relaxed or experienced positive selection. In addition, we describe here, for the first time, that the OXTR, AVPR1a, AVPR1b, and AVPR2 mammalian orthologues preserve their disorder content, while this condition varies among the paralogues. Finally, our results reveal the presence of short linear interaction motifs, indicating possible functional adaptations related to physiological and/or behavioral taxa-specific traits.
Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits
Frontiers in Neuroscience, 2016
Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date.
ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin—AVPR1A, AVPR1B, and OXTR
Background: There are limited treatments available for autism spectrum disorder (ASD). Studies have reported significant associations between the receptor genes of oxytocin (OT) and vasopressin (AVP) and ASD diagnosis, as well as ASD-related phenotypes. Researchers have also found the manipulation of these systems affects social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin (AVPR1A, AVPR1B), oxytocin (OXTR), and ASD diagnosis along with related subphenotypes.