Functional microsatellite polymorphism associated with divergent social structure in vole species.

Forebrain vasopressin/vasotocin systems regulate a diverse set of complex social behaviors in a species-specific manner. Among mammals, vasopressin gene sequences and peptide distributions in the brain are highly conserved across species. In contrast, vasopressin V1a receptors (V1aR) are conserved at the protein level, but not at the level of gene structure or neuroanatomical distribution of the receptor. Here, we examine the functional role of a microsatellite segment in the 5' region of V1aR that differs significantly between monogamous and nonmonogamous vole species with divergent V1aR expression patterns. Using luciferase reporter assays, we demonstrate that this microsatellite plays a significant role in transcriptional regulation in a cell-type-specific manner. These results suggest that significant evolutionary changes in social behavior can occur through variation in regulatory regions of genes already involved in social behavior.

[1]  C. Ferris,et al.  Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  D. Charlesworth,et al.  Breeding systems and genome evolution. , 2001, Current opinion in genetics & development.

[3]  T. Insel,et al.  Species differences in V1a receptor gene expression in monogamous and nonmonogamous voles: behavioral consequences. , 1997, Behavioral neuroscience.

[4]  L. Young,et al.  Variation in the vasopressin V1a receptor promoter and expression: implications for inter‐ and intraspecific variation in social behaviour * , 2002, The European journal of neuroscience.

[5]  A. Rich,et al.  A polymorphic dinucleotide repeat in the rat nucleolin gene forms Z-DNA and inhibits promoter activity , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Andrew H. Bass,et al.  Social behavior functions and related anatomical characteristics of vasotocin/vasopressin systems in vertebrates , 2001, Brain Research Reviews.

[7]  H. Willard,et al.  Study of V(1)-vascular vasopressin receptor gene microsatellite polymorphisms in human essential hypertension. , 2000, Journal of molecular and cellular cardiology.

[8]  S. Tapscott,et al.  CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus , 2001, Nature Genetics.

[9]  Goodson,et al.  Effect of Intraseptal Vasotocin and Vasoactive Intestinal Polypeptide Infusions on Courtship Song and Aggression in the Male Zebra Finch (Taeniopygia guttata) , 1999, Journal of neuroendocrinology.

[10]  K. Ross,et al.  Identification of a Major Gene Regulating Complex Social Behavior , 2001, Science.

[11]  Gene expression tomography. , 2002, Physiological genomics.

[12]  T. Insel,et al.  Immunoreactivity of central vasopressin and oxytocin pathways in microtine rodents: A quantitative comparative study , 1996, The Journal of comparative neurology.

[13]  K. Ross.  Molecular ecology of social behaviour: analyses of breeding systems and genetic structure , 2001, Molecular ecology.

[14]  D. Dewsbury,et al.  Differences in affiliative behavior, pair bonding, and vaginal cytology in two species of vole (Microtus ochrogaster and M. montanus). , 1990, Journal of comparative psychology.

[15]  H. Willard,et al.  Study of V1-vascular Vasopressin Receptor Gene Microsatellite Polymorphisms in Human Essential Hypertension☆ , 2000 .

[16]  T. Insel,et al.  Facilitation of Affiliation and Pair-Bond Formation by Vasopressin Receptor Gene Transfer into the Ventral Forebrain of a Monogamous Vole , 2001, The Journal of Neuroscience.

[17]  J. Goodson.  Territorial Aggression and Dawn Song are Modulated by Septal Vasotocin and Vasoactive Intestinal Polypeptide in Male Field Sparrows (Spizella pusilla) , 1998, Hormones and Behavior.

[18]  B. Leventhal,et al.  Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism , 2002, Molecular Psychiatry.

[19]  T. Insel,et al.  Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole , 1999, Nature.

[20]  E. Birney,et al.  Comparative genomics: genome-wide analysis in metazoan eukaryotes , 2003, Nature Reviews Genetics.

[21]  G. Robinson,et al.  Social behavior and comparative genomics: new genes or new gene regulation? , 2002, Genes, brain, and behavior.

[22]  J. Goodson,et al.  Vasotocin and vasoactive intestinal polypeptide modulate aggression in a territorial songbird, the violet-eared waxbill (Estrildidae: Uraeginthus granatina). , 1998, General and comparative endocrinology.

[23]  L. Young,et al.  Vasopressin-dependent neural circuits underlying pair bond formation in the monogamous prairie vole , 2004, Neuroscience.

[24]  M. Bannon,et al.  The dopamine transporter gene (SLC6A3) variable number of tandem repeats domain enhances transcription in dopamine neurons , 2001, Journal of neurochemistry.