Elsevier

Advances in Genetics

Volume 59, 2007, Pages 107-127
Advances in Genetics

Gene Regulation as a Modulator of Social Preference in Voles

https://doi.org/10.1016/S0065-2660(07)59004-8Get rights and content

Abstract

Most mammalian species are nonmonogamous: the female alone cares for the young and males and females do not share nest sites. Within the genus Microtus, there exists ample diversity in social structure for neuroethological and neurobiological investigation. Prairie voles (Microtus ochrogaster) are socially monogamous: both the males and females contribute to care of the young within a shared nest site as a breeding pair through multiple breeding seasons. Closely related species such as the montane (M. montanus) and meadow (M. pennsylvanicus) voles do not typically show these behaviors. Over a decade of research has demonstrated that species differences in neuropeptide systems play significant roles in the behavioral divergence of these species. In particular, species differences in regional gene expression patterns of neuropeptide receptors in the brain mediate some of the behavioral traits associated with the divergence in social structure. Differences in gene expression patterns of a key gene in mediating social behavior, the arginine vasopressin 1a receptor (avpr1a), appear to be due to species divergence in a repeat locus in the 5′ regulatory region of avpr1a. This highly repetitive locus is prone to expansion and contraction over relatively short evolutionary timescales and may give rise to the rapid evolution of sociobehavioral traits.

Introduction

The conserved “nuclear unit” (Wilson, 1975) of the mammalian social group is the maternal–infant interaction, which is a defining mammalian trait. Because mammalian neonates require mother's milk for survival, females (and neonates) face substantial selection pressure to maintain evolved neurobiological mechanisms that support maternal–infant interaction. Even though the mammalian nuclear unit is highly conserved, the quantity of maternal care and the quality of the interaction are not conserved. The presence of social bonding outside of the maternal–infant interaction is also not conserved. Additionally, females are the rate‐limiting resource in sexual selection in mammals, so polygamy is standard. Male mammals face very little selection pressure to evolve or maintain neurobiological mechanisms of social bonding. This is reflected in the rarity of monogamous social structures among mammals, which is estimated at 3–5% (Kleiman, 1977). Those rare cases of monogamous social structure among mammals appear to reflect harsher environmental conditions where pair bonding and paternal care increase reproductive fitness (Emlen and Oring, 1977). Therefore, for a species to be monogamous, something in the neurobiology of social behavior has to change dramatically. Monogamy, even though rare, has emerged multiple times across diverse mammalian taxa. The repeated appearance of monogamous social structure in distantly related taxa and the diversity of social structure among closely related species suggest that these dramatic changes in underlying neurobiology must happen rapidly, independently, and perhaps reversibly.

From an ecological perspective, lactation certainly is a driving force of mammalian evolution, and the neuropeptide oxytocin is a key player in the biology of lactation. Wilson's (1975) insightful thoughts on the role of milk in the sociobiology of mammals preceded the experimental evidence for the role of oxytocin in the neurobiology of mammalian social behavior. In addition to its role in lactation, oxytocin is co‐opted in the brain and influences the neurobiology of maternal–infant interaction. Oxytocin was discovered in 1909 by Sir Henry Dale (1909) and first synthesized in 1953 by Vincent du Vigneaud (du Vigneaud et al., 1954), for which he received the 1955 Nobel Prize in chemistry. Oxytocin is the product of a gene duplication event that also produced the paralogous gene encoding the neuropeptide arginine vasopressin (also known as antidiuretic hormone). Both oxytocin and vasopressin are 9‐amino acid peptides that are produced and released within the brain as well as into general circulation via the posterior pituitary. The genes encoding oxytocin and vasopressin face each other on the same chromosome in the mammalian genome (Burbach et al., 2001) and share common gene regulatory elements in the noncoding region between the two coding loci (Fields et al., 2003), even though they are not expressed in the same neurons (Mohr et al., 1988). The two genes derived from a phylogenetically ancient family of peptides which also includes nonmammalian vasotocin, mesotocin, isotocin, conopressin, and even annetocin from annelida. Homologues of oxytocin and vasopressin are evident in extant invertebrates indicating that the precursor to the oxytocin/vasopressin superfamily was present at least 500 million years ago (Satake 1999, Van Kesteren 1995). Peripherally, these peptides serve to regulate physiological homeostasis, especially water and salt balance. With an expanding nervous system across evolutionary timescales, these peptide systems have been put to use in the central nervous system to regulate behavioral aspects of homeostatic control. In this role, these peptide systems act within the brain to modulate approach/avoid responses to various stimuli, including the approach/avoid dichotomy in social behavior.

Section snippets

Oxytocin

Oxytocin and vasopressin, acting within the brain, appear to play key roles in mammalian sociobehavioral strategies. In the early 1990s, drawing on decades of work on the role of oxytocin in maternal–infant interactions (Kendrick 1987, Pedersen 1979), Carter et al. (1992) postulated that oxytocin may play a role in the neurobiology of adult bonding. This hypothesis was tested in the prairie vole (Microtus ochrogaster), which is a socially monogamous rodent species (Getz 1981, Thomas 1979).

Vasopressin

While the effects of oxytocin on social behavior were being studied in females, the related neuropeptide, vasopressin, was found to modulate pair bonding in male prairie voles. Prior to the studies in voles, there were early indications that vasopressin might play a role in the brain as a modulator of social behavior. For example, central injection of vasopressin into the medial preoptic area resulted in the onset of stereotypic flank‐marking behavior in male and female golden hamsters (Ferris

Comparative genetics

Caveats aside, receptor distribution patterns do appear to play a role in the modulation of species‐typical social behavior. This raises the obvious question of what regulates receptor distribution patterns. Gene sequence comparisons between montane and prairie voles of the gene encoding V1aR (avpr1a) have implicated species differences in gene regulatory mechanisms.

The coding regions between montane vole and prairie vole avpr1a share 99% identity. There are four amino acid changes out of 420

Sexual Dimorphism

This chapter has presented a view of the role of oxytocin and vasopressin systems in female and male species‐typical social behavior, respectively. This sexually dimorphic presentation is quite simplistic, and it is therefore important to point out that oxytocin systems can modulate male sociosexual behaviors and, as well, vasopressin can modulate female sociosexual behaviors (Cho et al., 1999). Further, as mentioned previously, the behavioral influence of the neuropeptides oxytocin and

Coda

Finally, the exploration of the neurobiology of social bonding began with an extension of an idea about the importance of milk in the neurobiology of mammals. Chronologically, these investigations first involved oxytocin and later vasopressin. However, in the evolutionary history of mammals, both oxytocin and vasopressin were present from the start. The conserved brain distribution of these two neuropeptides, their structural similarities, and cross talk among receptors, albeit with varying

Acknowledgments

I would like to thank Larry J. Young, Ph.D. of Emory University and Pat Levitt, Ph.D. of Vanderbilt University for mentorship, and Drs. Kathie Eagleson, Daniel Campbell and, Barbara Thompson for helpful comments on this chapter. I would also like to acknowledge recent support from NIH F31MH67397 and NIH T32MH65215 and current support from NIH T32MH075883.

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