Genetic Diversity of Microsatellite RS3 in AVPR1a Promoter Region in Primates

Rapid Communication

Austin J Biotechnol Bioeng. 2014;1(4): 3.

Genetic Diversity of Microsatellite RS3 in AVPR1a Promoter Region in Primates

Dongren Ren1,2,3*

1Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, China

2Department of Psychology, University of Nebraska at Omaha, USA

3Department of Biology, University of Nebraska at Omaha, USA

*Corresponding author: Ren D, Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Department of Psychology & Biology, University of Nebraska at Omaha, USA.

Received: September 30, 2014; Accepted: October 07, 2014; Published: October 09, 2014

Abstract

The neurohypophyseal hormone Arginine Vasopressin (AVP) and its receptor type 1a (AVPR1a) play important roles in the modulation of social behaviors in mammals. RS3 microsatellites in the AVPR1a promoter region have been implicated in influencing social behavior. However, the relationship between RS3 diversity and social monogamy in primates is not clear. In this study, RS3 sequences from 18 primate species and 24 individuals were collected and aligned, and association between RS3 and social monogamy were analyzed. Though genetic diversity of RS3 was found in these animals, no significant association was observed here (P> 0.05). Results in this study enhance the appreciation of genetic diversity in the mammalian AVPR1a system, and set the stage for studies in the molecular diversity of the neurohypophysial hormones and social behavior in primates.

Keywords: Neuropeptide; RS3; Monogamy; Primate

Abbreviations

AVP: Arginine Vasopressin; AVPR1a: Arginine Vasopressin Receptor Type 1a; NWM: New World Monkeys; RS3: Microsatellites in AVPR1a promoter

Introduction

The neurohypophysial hormone Arginine Vasopressin (AVP) is synthesizedprimarily in the Paraventricular Nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Through its two centrally expressed receptor subtypes (AVPR1a and AVPR1b), AVP has a variety of neurological effects on the social behaviors [1-4]. In primates, male titi monkeys receiving intranasal AVP treatments contacted their partner more frequently than the stranger [5]. Intranasal delivery of AVP has also been reported to affect social communication processes in men and women [6].

Of these two centrally expressed receptors, AVPR1a plays a more prominent role in vasopressinergic modulation of social behavior. Brain AVPR1a distribution differs considerably between monogamous voles (prairie voles) and non-monogamous voles (montane and meadow voles) [7] and forebrain AVPR1a expression is associated with sexual and social fidelity in male prairie voles [8]. For brain AVPR1a density, down-regulation of AVPR1adensity resulted in a clear impairment in the preference for a mated female partner and a reduction in anxiety-like behavior in adulthood [9]. Central AVPR1a activation is necessary for both partner preference formation and expression in male prairie voles [10]. Increased brain AVPR1a density enhanced the partner preference of meadow voles [11].Male marmosets show paternal behavior, and the prefrontal cortex of marmoset fathers display increased density of dendritic spines and enhanced expression of AVPR1a in these spines [12], suggesting that AVPR1a plays a role in paternal care. Note that genetic polymorphisms, such as the microsatellites in AVPR1a promoter (RS3), have been implicated in social behavior in mammals. In humans, there is a complex RS3 located in the 5' flanking region of AVPR1a, and at least 16 alleles were observed [13]. Previous studies demonstrated that RS3is associated with human autism [14-16], sexual behavior [17, 18], altruism [19], maternal behaviors [20], and pair bonding in men [21]. Additionally, RS3 alleles in healthy humans are associated with increased activation of amygdale, an important area for pair bonding formation [22]. Recently, RS3 is associated with social personality in chimpanzee [23].

However, to our knowledge, there are no comprehensive data regarding RS3 variation in primates, and its relationship with one of important social behaviors, social monogamy, is also unclear. Therefore, all available published data of RS3 sequences in primates were collected and analyzed in this study.

Materials and Methods

Sequences

All available public RS3 sequences were collected from NCBI, UCSC Genome Browser, Ensembl, and literatures, which are involved in a total of 24 individuals from 18primate species.

Social monogamy definition

Social monogamy (not genetic monogamy) in mammals refers to a long term or sequential living arrangement between an adult male and an adult female. This arrangement is frequently defined as: sharing the same territory, obtaining food resources, and raising offspring together. The presence or absence of social monogamy in primates was based on recent surveys [24, 25].

Statistical analysis

Statistical significance of RS3repeats between the social monogamous and non-social monogamous species were evaluated by ANOVA (in IBM SPSS Statistics 20, SPSS In., U.S.A). The significance level was set at P< 0.05.

Results

All publically available RS3 data were collected and aligned based on the three literatures [26-28]. A total of 24 animals were obtained in this alignment (Figure 1). Species Aotus did not show the RS3 alleles, which was replaced by microsatellite "GTATATAC". One of Pan troglodytes also did not show a RS3 region[27]. Of the CT4 in RS3, other five variations were identified, including CT0, CT2, CT5, CT7 and CT9. Other 11 and 8 types of CT8and GT24in RS3 were observed in these species (Figure 1). Although the microsatellites show marked variability in primates, no association was observed between RS3 alleles and social monogamy (P> 0.05). Attempts were made to amplify the RS3 regions of social monogamous species, like Callithrix jacchus, Leontopithecus rosalia, and Callimico goeldii. However these PCRs were unsuccessful.

Figure 1: RS3 alignment in monogamous species (shaded) and non-monogamous species, with- indicating a gap; and 1, 2, 3 represent reference [26], reference [27] and reference [28], respectively.






Figure 1:  RS3 alignment in monogamous species (shaded) and non-monogamous species, with- indicating a gap; and 1, 2, 3 represent reference [26], reference [27] and reference [28], respectively.

Discussion

Among the primates, the regular expression of social monogamy is rare or absent in prosimian and Old World primate genera. In hominoid primates (apes and humans), social monogamy is noted in gibbons, siamangs and human, but not in other hominoid genera. In contrast, social monogamy is relatively prevalent in New World Monkeys (NWM), with 50% of genera routinely displaying this social system[24,25,29]. Since AVP and AVPR1a are implicated in social behavior [7-12,30,31], the aim of this study was to investigate whether genetic variability of RS3 in AVPR1a are associated with social monogamy in primates.

There is increasing evidence that RS3 of AVPR1a is associated with social behavior [13-23]. In this study, the RS3 region in some social monogamous species were attempted to be amplified and sequenced, but ultimately failed, which coincides with previous reports [28]. Therefore, in this study, all public ally available RS3 data in primates were collected, aligned and analyzed, including six monogamous species and 12 non-monogamous species (24 animals; Figure 1). However, the polymorphic RS3 in this study did not demonstrate any association with social monogamy in primates (P> 0.05). Our findings agree with previous results that found no general association between RS3 polymorphisms and social behavior across part of primate tax [26,27]. Notably, RS3 is completely absent in monogamous Owl monkeys (Aotusazarai) [28]. A recent study also indicates the complex relationship between AVRP1a and social monogamy [32]. Whether RS3is associated with social monogamy in primates needs to be investigated in future.

In conclusion, although RS3 genetic diversity was found in these primate species, no significant association was observed between RS3 and social monogamy in primates.

References

  1. Cho MM, DeVries AC, Williams JR, Carter CS. The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). Behav Neurosci. 1999; 113: 1071-1079.
  2. Bosch OJ, Neumann ID. Brain vasopressin is an important regulator of maternal behavior independent of dams' trait anxiety. Proc Natl Acad Sci U S A. 2008; 105: 17139-17144.
  3. Bosch OJ, Neumann ID. Vasopressin released within the central amygdala promotes maternal aggression. Eur J Neurosci. 2010; 31: 883-891.
  4. Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci. 2002; 5: 514-516.
  5. Jarcho MR, Mendoza SP, Mason WA, Yang X, Bales KL. Intranasal vasopressin affects pair bonding and peripheral gene expression in male Callicebus cupreus. Genes Brain Behav. 2011; 10: 375-383.
  6. Thompson RR, George K, Walton JC, Orr SP, Benson J. Sex-specific influences of vasopressin on human social communication. Proc Natl Acad Sci U S A. 2006; 103: 7889-7894.
  7. Insel TR, Wang ZX, Ferris CF. Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents. J Neurosci. 1994; 14: 5381-5392.
  8. Ophir AG, Wolff JO, Phelps SM. Variation in neural V1aR predicts sexual fidelity and space use among male prairie voles in semi-natural settings. Proc Natl Acad Sci U S A. 2008; 105: 1249-1254.
  9. Barrett CE, Keebaugh AC, Ahern TH, Bass CE, Terwilliger EF, Young LJ. Variation in vasopressin receptor (Avpr1a) expression creates diversity in behaviors related to monogamy in prairie voles. Horm Behav. 2013; 63: 518-526.
  10. Donaldson ZR, Spiegel L and Young LJ. Central vasopressin V1a receptor activation is independently necessary for both partner preference formation and expression in socially monogamous male prairie voles. Behav Neurosci. 2010; 124: 159-163.
  11. Lim MM, Wang Z, Olazábal DE, Ren X, Terwilliger EF, Young LJ. Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature. 2004; 429: 754-757.
  12. Kozorovitskiy Y, Hughes M, Lee K, Gould E. Fatherhood affects dendritic spines and vasopressin V1a receptors in the primate prefrontal cortex. Nat Neurosci. 2006; 9: 1094-1095.
  13. Thibonnier M, Graves MK, Wagner MS, Chatelain N, Soubrier F, Corvol P, et al. Study of V(1)-vascular vasopressin receptor gene microsatellite polymorphisms in human essential hypertension. J Mol Cell Cardiol. 2000; 32: 557-564.
  14. Kim SJ, Young LJ, Gonen D, Veenstra-VanderWeele J, Courchesne R, Courchesne E, et al. Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Mol Psychiatry. 2002; 7: 503-507.
  15. Wassink TH, Piven J, Vieland VJ, Pietila J, Goedken RJ, Folstein SE, et al. Examination of AVPR1a as an autism susceptibility gene. Mol Psychiatry. 2004; 9: 968-972.
  16. Yirmiya N, Rosenberg C, Levi S, Salomon S, Shulman C, Nemanov L, et al. Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills. Mol Psychiatry. 2006; 11: 488-494.
  17. Prichard ZM, Mackinnon AJ, Jorm AF, Easteal S. AVPR1A and OXTR polymorphisms are associated with sexual and reproductive behavioral phenotypes in humans. Mutation in brief no. 981. Online. Hum Mutat. 2007; 28: 1150.
  18. Guastella AJ, Kenyon AR, Unkelbach C, Alvares GA, Hickie IB. Arginine Vasopressin selectively enhances recognition of sexual cues in male humans. Psychoneuroendocrinology. 2011; 36: 294-297.
  19. Knafo A, Israel S, Darvasi A, Bachner-Melman R, Uzefovsky F, Cohen L, et al. 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. 2008; 7: 266-275.
  20. Avinun R, Ebstein RP, Knafo A. Human maternal behaviour is associated with arginine vasopressin receptor 1A gene. Biol Lett. 2012; 8: 894-896.
  21. Walum H, Westberg L, Henningsson S, Neiderhiser JM, Reiss D, Igl W, et al. Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans. Proc Natl Acad Sci U S A. 2008; 105: 14153-14156.
  22. Meyer-Lindenberg A, Kolachana B, Gold B, Olsh A, Nicodemus KK, Mattay V, et al. Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol Psychiatry. 2009; 14: 968-975.
  23. Hopkins WD, Donaldson ZR, Young LJ. 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 Behav. 2012; 11: 552-558.
  24. Lukas D, Clutton-Brock TH. The evolution of social monogamy in mammals. Science. 2013; 341: 526-530.
  25. Opie C, Atkinson QD, Dunbar RI, Shultz S. Male infanticide leads to social monogamy in primates. Proc Natl Acad Sci U S A. 2013; 110: 13328-13332.
  26. Donaldson ZR, Kondrashov FA, Putnam A, Bai Y, Stoinski TL, Hammock EA, et al. Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene. BMC Evol Biol. 2008; 8: 180.
  27. Rosso L, Keller L, Kaessmann H, Hammond RL. Mating system and avpr1a promoter variation in primates. Biol Lett. 2008; 4: 375-378.
  28. Babb PL, Fernandez-Duque E, Schurr TG. AVPR1A sequence variation in monogamous owl monkeys (Aotus azarai) and its implications for the evolution of platyrrhine social behavior. J Mol Evol. 2010; 71: 279-297.
  29. Solomon NG, French JA. Cooperative breeding in mammals. New York: Cambridge University Press. 1997; 1-10.
  30. Nephew BC, Bridges RS. Central actions of arginine vasopressin and a V1a receptor antagonist on maternal aggression, maternal behavior, and grooming in lactating rats. Pharmacol Biochem Behav. 2008; 91: 77-83.
  31. Young LJ, Nilsen R, Waymire KG, MacGregor GR, Insel TR. Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole. Nature. 1999; 400: 766-768.
  32. Ren D, Chin KR and French JA. Molecular variation in AVP and AVPR1a in New World monkeys (Primates, Platyrrhini): evolution and implications for social monogamy. Plos One. 2014.

Citation: Ren D. Genetic Diversity of Microsatellite RS3 in AVPR1a Promoter Region in Primates. Austin J Biotechnol Bioeng. 2014;1(4): 3. ISSN: 2378-3036