Evolution of the arginine vasopressin 1a receptor and implications for mammalian social behaviour.

Variation in social and mating behaviour among individuals or species can rarely be traced to its genetic basis. A notable exception is social behaviour in Microtus voles, which has been causally linked to polymorphisms in the arginine vasopressin 1a receptor (Avpr1a) gene region. A repetitive expansion in the promoter region of Avpr1a was interpreted as causally related to monogamy based on the results of inter-specific gene transfer, transcription assays and the presence-absence patterns in four Microtus species. The examination of further Microtus species and other mammals revealed that single or multiple short tandem repeats (STRs) upstream of Avpr1a are widespread in rodents. Phylogenetic analyses suggest that their absence in two closely related Microtus species is the result of an evolutionarily recent loss. Presence-absence patterns of the repetitive expansion show overall no association with mating and social system parameters in rodents. Similar STRs upstream of the Avpr1a gene in humans and primates are distinct in position and motif from those in rodents. Examination of the coding region (exon 1) of Avpr1a reveals unexpectedly high levels of genetic variation within the genus Microtus as well as in other mammalian taxa. Deleterious variation is largely eliminated by purifying selection on most regions of exon 1, but some sites in domains with particularly high rates of change are under positive selection in mammals. Variation in Avpr1a is likely of functional importance due to length variation in amino acid sequences, radical amino acid replacements and amino acid heterozygosity of individuals. It appears that intra-specific and intra-individual variation in both regulatory and coding regions deserves explicit consideration when causal links between genotype and phenotype are to be established.