The Relative Contribution of Proximal 5′ Flanking Sequence and Microsatellite Variation on Brain Vasopressin 1a Receptor () Gene Expression and Behavior
Certain genes exhibit notable diversity in their expression patterns both within and between species. One such gene is the vasopressin receptor 1a gene (Avpr1a), which exhibits striking differences in neural expression patterns that are responsible for mediating differences in vasopressin-mediated social behaviors. The genomic mechanisms that contribute to these remarkable differences in expression are not well understood. Previous work has suggested that both the proximal 5′ flanking region and a polymorphic microsatellite element within that region of the vole Avpr1a gene are associated with variation in V1a receptor (V1aR) distribution and behavior, but neither has been causally linked. Using homologous recombination in mice, we reveal the modest contribution of proximal 5′ flanking sequences to species differences in V1aR distribution, and confirm that variation in V1aR distribution impacts stress-coping in the forced swim test. We also demonstrate that the vole Avpr1a microsatellite structure contributes to Avpr1a expression in the amygdala, thalamus, and hippocampus, mirroring a subset of the inter- and intra-species differences observed in central V1aR patterns in voles. This is the first direct evidence that polymorphic microsatellite elements near behaviorally relevant genes can contribute to diversity in brain gene expression profiles, providing a mechanism for generating behavioral diversity both at the individual and species level. However, our results suggest that many features of species-specific expression patterns are mediated by elements outside of the immediate 5′ flanking region of the gene.
Vyšlo v časopise:
The Relative Contribution of Proximal 5′ Flanking Sequence and Microsatellite Variation on Brain Vasopressin 1a Receptor () Gene Expression and Behavior. PLoS Genet 9(8): e32767. doi:10.1371/journal.pgen.1003729
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003729
Souhrn
Certain genes exhibit notable diversity in their expression patterns both within and between species. One such gene is the vasopressin receptor 1a gene (Avpr1a), which exhibits striking differences in neural expression patterns that are responsible for mediating differences in vasopressin-mediated social behaviors. The genomic mechanisms that contribute to these remarkable differences in expression are not well understood. Previous work has suggested that both the proximal 5′ flanking region and a polymorphic microsatellite element within that region of the vole Avpr1a gene are associated with variation in V1a receptor (V1aR) distribution and behavior, but neither has been causally linked. Using homologous recombination in mice, we reveal the modest contribution of proximal 5′ flanking sequences to species differences in V1aR distribution, and confirm that variation in V1aR distribution impacts stress-coping in the forced swim test. We also demonstrate that the vole Avpr1a microsatellite structure contributes to Avpr1a expression in the amygdala, thalamus, and hippocampus, mirroring a subset of the inter- and intra-species differences observed in central V1aR patterns in voles. This is the first direct evidence that polymorphic microsatellite elements near behaviorally relevant genes can contribute to diversity in brain gene expression profiles, providing a mechanism for generating behavioral diversity both at the individual and species level. However, our results suggest that many features of species-specific expression patterns are mediated by elements outside of the immediate 5′ flanking region of the gene.
Zdroje
1. YoungLJ, WangZ (2004) The neurobiology of pair bonding. Nat Neurosci 7: 1048–1054.
2. PhelpsSM, CampbellP, ZhengDJ, OphirAG (2010) Beating the boojum: comparative approaches to the neurobiology of social behavior. Neuropharmacology 58: 17–28.
3. RennSC, Aubin-HorthN, HofmannHA (2008) Fish and chips: functional genomics of social plasticity in an African cichlid fish. The Journal of experimental biology 211: 3041–3056.
4. GoodsonJL, KellyAM, KingsburyMA (2012) Evolving nonapeptide mechanisms of gregariousness and social diversity in birds. Horm Behav 61: 239–250.
5. FuentesA (2002) Patterns and Trends in Primate Pair Bonds. International Journal of Primatology 23: 953.
6. ThierryB, IwaniukAN, PellisSM (2000) The Influence of Phylogeny on the Social Behaviour of Macaques (Primates: Cercopithecidae, genus Macaca). Ethology 106: 713–728.
7. SternDL, OrgogozoV (2009) Is genetic evolution predictable? Science 323: 746–751.
8. PreussTM, CaceresM, OldhamMC, GeschwindDH (2004) Human brain evolution: insights from microarrays. Nature reviews Genetics 5: 850–860.
9. de BonoM, BargmannCI (1998) Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans. Cell 94: 679–689.
10. BrittenRJ, DavidsonEH (1969) Gene Regulation for Higher Cells: A Theory. Science 165: 349–357.
11. VincesMD, LegendreM, CaldaraM, HagiharaM, VerstrepenKJ (2009) Unstable Tandem Repeats in Promoters Confer Transcriptional Evolvability. Science 324: 1213–1216.
12. TrifonovEN (1989) The multiple codes of nucleotide sequences. Bulletin of mathematical biology 51: 417–432.
13. KingMC, WilsonAC (1975) Evolution at two levels in humans and chimpanzees. Science 188: 107–116.
14. HoekstraHE, CoyneJA (2007) The locus of evolution: evo devo and the genetics of adaptation. Evolution 61: 995–1016.
15. FederME (2007) Evolvability of physiological and biochemical traits: evolutionary mechanisms including and beyond single-nucleotide mutation. The Journal of experimental biology 210: 1653–1660.
16. FondonJW (2008) Simple sequence repeats: genetic modulators of brain function and behavior. Trends Neurosci 31: 328–334.
17. HammockEA, YoungLJ (2005) Microsatellite instability generates diversity in brain and sociobehavioral traits. Science 308: 1630–1634.
18. EngelmannM, LandgrafR, WotjakCT (2004) The hypothalamic-neurohypophysial system regulates the hypothalamic-pituitary-adrenal axis under stress: an old concept revisited. Frontiers in neuroendocrinology 25: 132–149.
19. WinslowJT, HastingsN, CarterCS, HarbaughCR, InselTR (1993) A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365: 545–548.
20. InselTR (2010) The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron 65: 768–779.
21. Meyer-LindenbergA, DomesG, KirschP, HeinrichsM (2011) Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nature Reviews Neuroscience 12: 524–538.
22. Caldwell HK, Young III WS (2006) Oxytocin and Vasopressin: Genetics and Behavioural Implications. In: Lim R, editor. Handbook or Neurochemistry and Molecular Neurobiology, 3rd Edition. New York: Springer. pp. 573–607.
23. DonaldsonZR, YoungLJ (2008) Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322: 900–904.
24. YoungLJ, NilsenR, WaymireKG, MacGregorGR, InselTR (1999) Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole. Nature 400: 766–768.
25. YoungLJ (1999) Frank A. Beach Award. Oxytocin and vasopressin receptors and species-typical social behaviors. Horm Behav 36: 212–221.
26. YoungLJ, WinslowJT, NilsenR, InselTR (1997) Species differences in V1a receptor gene expression in monogamous and nonmonogamous voles: behavioral consequences. Behav Neurosci 111: 599–605.
27. WangZ, YoungLJ, LiuY, InselTR (1997) Species differences in vasopressin receptor binding are evident early in development: comparative anatomic studies in prairie and montane voles. J Comp Neurol 378: 535–546.
28. InselTR, WangZX, FerrisCF (1994) Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents. J Neurosci 14: 5381–5392.
29. LimMM, YoungLJ (2004) Vasopressin-dependent neural circuits underlying pair bond formation in the monogamous prairie vole. Neuroscience 125: 35–45.
30. LandgrafR, FrankE, AldagJM, NeumannID, SharerCA, et al. (2003) Viral vector-mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behaviour. Eur J Neurosci 18: 403–411.
31. PitkowLJ, SharerCA, RenX, InselTR, TerwilligerEF, et al. (2001) Facilitation of affiliation and pair-bond formation by vasopressin receptor gene transfer into the ventral forebrain of a monogamous vole. J Neurosci 21: 7392–7396.
32. GobroggeKL, LiuY, YoungLJ, WangZ (2009) Anterior hypothalamic vasopressin regulates pair-bonding and drug-induced aggression in a monogamous rodent. Proc Natl Acad Sci U S A 106: 19144–19149.
33. BarrettCE, KeebaughAC, AhernTH, BassCE, TerwilligerEF, et al. (2013) Variation in vasopressin receptor (Avpr1a) expression creates diversity in behaviors related to monogamy in prairie voles. Horm Behav 63: 518–26.
34. LimMM, WangZ, OlazabalDE, RenX, TerwilligerEF, et al. (2004) Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 429: 754–757.
35. HammockEA, YoungLJ (2004) Functional microsatellite polymorphism associated with divergent social structure in vole species. Mol Biol Evol 21: 1057–1063.
36. HammockEA, LimMM, NairHP, YoungLJ (2005) Association of vasopressin 1a receptor levels with a regulatory microsatellite and behavior. Genes Brain Behav 4: 289–301.
37. OphirAG, CampbellP, HannaK, PhelpsSM (2008) Field tests of cis-regulatory variation at the prairie vole avpr1a locus: association with V1aR abundance but not sexual or social fidelity. Horm Behav 54: 694–702.
38. EbsteinRP, KnafoA, MankutaD, ChewSH, LaiPS (2012) The contributions of oxytocin and vasopressin pathway genes to human behavior. Horm Behav 61: 359–379.
39. HopkinsWD, DonaldsonZR, YoungLJ (2012) A polymorphic indel containing the RS3 microsatellite in the 5′ flanking region of the vasopressin V1a receptor gene is associated with chimpanzee (Pan troglodytes) personality. Genes, brain, and behavior 11: 552–558.
40. JarneP, LagodaPJ (1996) Microsatellites, from molecules to populations and back. Trends in Ecology & Evolution 11: 424–429.
41. QuandtK, FrechK, KarasH, WingenderE, WernerT (1995) MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. Nucleic Acids Res 23: 4878–4884.
42. MGI Mouse SNP Query, Mouse Genome Informatics website, The Jackson Laboratory, Bar Harbor, Maine. http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=snpQF). Accessed May, 2013.
43. EppigJT, BlakeJA, BultCJ, KadinJA, RichardsonJE (2012) The Mouse Genome Database (MGD): comprehensive resource for genetics and genomics of the laboratory mouse. Nucleic Acids Res 40: D881–886.
44. WangZ, LiuY, YoungLJ, InselTR (1997) Developmental changes in forebrain vasopressin receptor binding in prairie voles (Microtus ochrogaster) and montane voles (Microtus montanus). Ann N Y Acad Sci 807: 510–513.
45. BielskyIF, HuSB, RenX, TerwilligerEF, YoungLJ (2005) The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study. Neuron 47: 503–513.
46. EbnerK, WotjakCT, LandgrafR, EngelmannM (2002) Forced swimming triggers vasopressin release within the amygdala to modulate stress-coping strategies in rats. The European journal of neuroscience 15: 384–388.
47. YangJ, PanYJ, YinZK, HaiGF, LuL, et al. (2012) Effect of arginine vasopressin on the behavioral activity in the behavior despair depression rat model. Neuropeptides 46: 141–149.
48. EngelmannM, WotjakCT, NeumannI, LudwigM, LandgrafR (1996) Behavioral Consequences of Intracerebral Vasopressin and Oxytocin: Focus on Learning and Memory. Neuroscience & Biobehavioral Reviews 20: 341–358.
49. van Wimersma GreidanusTB, van ReeJM, de WiedD (1983) Vasopressin and memory. Pharmacol Ther 20: 437–458.
50. DennyCA, BurghardtNS, SchachterDM, HenR, DrewMR (2012) 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning. Hippocampus 22: 1188–1201.
51. BrownMW, AggletonJP (2001) Recognition memory: what are the roles of the perirhinal cortex and hippocampus? Nature Reviews Neuroscience 2: 51–61.
52. DubrovskyB, TatarinovA, GijsbersK, HarrisJ, TsiodrasA (2003) Effects of arginine-vasopressin (AVP) on long-term potentiation in intact anesthetized rats. Brain research bulletin 59: 467–472.
53. ChenC, Diaz BrintonRD, ShorsTJ, ThompsonRF (1993) Vasopressin induction of long-lasting potentiation of synaptic transmission in the dentate gyrus. Hippocampus 3: 193–203.
54. CarthariusK, FrechK, GroteK, KlockeB, HaltmeierM, et al. (2005) MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 21: 2933–2942.
55. McCarthyM (2006) Allen Brain Atlas maps 21,000 genes of the mouse brain. Lancet neurology 5: 907–908.
56. TiroshI, BarkaiN, VerstrepenKJ (2009) Promoter architecture and the evolvability of gene expression. Journal of biology 8: 95.
57. O'ConnellLA, HofmannHA (2012) Evolution of a vertebrate social decision-making network. Science 336: 1154–1157.
58. LynchM, SungW, MorrisK, CoffeyN, LandryCR, et al. (2008) A genome-wide view of the spectrum of spontaneous mutations in yeast. Proc Natl Acad Sci U S A 105: 9272–9277.
59. BelenkyM, CastelM, YoungWS (1992) Ultrastructural immunolocalization of rat oxytocin-neurophysin in transgenic mice expressing the rat oxytocin gene. Brain Res 583: 279–286.
60. HoMY, CarterDA, AngHL, MurphyD (1995) Bovine oxytocin transgenes in mice. Hypothalamic expression, physiological regulation, and interactions with the vasopressin gene. The Journal of Biological Chemistry 270: 27199–27205.
61. HoMY, MurphyD (1997) A bovine oxytocin transgene in mice: expression in the female reproductive organs and regulation during pregnancy, parturition and lactation. Molecular and cellular endocrinology 136: 15–21.
62. YoungWS (1990) Cell-specific expression of the rat oxytocin gene in transgenic mice. Journal of Neuroendocrinology 2: 917–925.
63. VenkateshB, Si-HoeSL, MurphyD, BrennerS (1997) Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes. Proceedings of the National Academy of Sciences of the United States of America 94: 12462–12466.
64. TurnerLM, YoungAR, RomplerH, SchonebergT, PhelpsSM, et al. (2010) Monogamy evolves through multiple mechanisms: evidence from V1aR in deer mice. Molecular biology and evolution 27: 1269–1278.
65. KashiY, KingD, SollerM (1997) Simple sequence repeats as a source of quantitative genetic variation. Trends Genet 13: 74–78.
66. KashiY, KingDG (2006) Simple sequence repeats as advantageous mutators in evolution. Trends Genet 22: 253–259.
67. RossoL, KellerL, KaessmannH, HammondRL (2008) Mating system and avpr1a promoter variation in primates. Biology letters 4: 375–378.
68. CurleyJP, JensenCL, FranksB, ChampagneFA (2012) Variation in maternal and anxiety-like behavior associated with discrete patterns of oxytocin and vasopressin 1a receptor density in the lateral septum. Horm Behav 61: 454–461.
69. FinkS, ExcoffierL, HeckelG (2006) Mammalian monogamy is not controlled by a single gene. Proc Natl Acad Sci U S A 103: 10956–10960.
70. YoungLJ, HammockEA (2007) On switches and knobs, microsatellites and monogamy. Trends Genet 23: 209–212.
71. DonaldsonZR, KondrashovFA, PutnamA, BaiY, StoinskiTL, et al. (2008) Evolution of a behavior-linked microsatellite-containing element in the 5′ flanking region of the primate AVPR1A gene. BMC Evol Biol 8: 180.
72. ThibonnierM, GravesMK, WagnerMS, ChatelainN, SoubrierF, et al. (2000) Study of V(1)-vascular vasopressin receptor gene microsatellite polymorphisms in human essential hypertension. J Mol Cell Cardiol 32: 557–564.
73. DavidDJ, KlemenhagenKC, HolickKA, SaxeMD, MendezI, et al. (2007) Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-m ethylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis. The Journal of Pharmacology and Experimental Therapeutics 321: 237–248.
74. KnafoA, IsraelS, DarvasiA, Bachner-MelmanR, UzefovskyF, et al. (2008) Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin 1a receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNA. Genes Brain Behav 7: 266–275.
75. Meyer-LindenbergA, KolachanaB, GoldB, OlshA, NicodemusKK, et al. (2008) Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol Psychiatry 14: 968–75.
76. EbsteinRP (2006) The molecular genetic architecture of human personality: beyond self-report questionnaires. Mol Psychiatry 11: 427–445.
77. Bachner-melmanR, ZoharAH, Bacon-ScnoorN, ElizurY, NemanovL, et al. (2005) Link between vasopressin receptor AVPR1A promoter region micorsatellites and measures of social behavior in humans. Journal of Individual Differences 26: 2–10.
78. WalumH, WestbergL, HenningssonS, NeiderhiserJM, ReissD, et al. (2008) Genetic variation in the vasopressin receptor 1a (AVPR1A) associates with pair-bonding behavior in humans. Proceedings of the National Academy of Sciences 105: 14153–14156.
79. WassinkTH, PivenJ, VielandVJ, PietilaJ, GoedkenRJ, et al. (2004) Examination of AVPR1a as an autism susceptibility gene. Mol Psychiatry 9: 968–972.
80. YirmiyaN, RosenbergC, LeviS, SalomonS, ShulmanC, et al. (2006) Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills. Mol Psychiatry 11: 488–494.
81. KimSJ, YoungLJ, GonenD, Veenstra-VanderWeeleJ, CourchesneR, et al. (2002) Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Mol Psychiatry 7: 503–507.
82. BielskyIF, HuS-B, RenX, TerwilligerEF, YoungLJ (2005) The V1a Vasopressin Receptor Is Necessary and Sufficient for Normal Social Recognition: A Gene Replacement Study. Neuron 47: 503–513.
83. PhelpsSM, YoungLJ (2003) Extraordinary diversity in vasopressin (V1a) receptor distributions among wild prairie voles (Microtus ochrogaster): patterns of variation and covariation. The Journal of comparative neurology 466: 564–576.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2013 Číslo 8
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