Molecular regulation of vasopressin receptor among (mostly) monogamous prairie voles

dc.contributor.advisorPhelps, Steven Michael, 1970-
dc.contributor.committeeMemberHofmann, Johann A
dc.contributor.committeeMemberVokes, Steven A
dc.contributor.committeeMemberMatz, Mikhail
dc.contributor.committeeMemberAtkinson, Nigel
dc.creatorOkhovat, Mariam
dc.creator.orcid0000-0002-3145-9397
dc.date.accessioned2019-01-15T15:52:48Z
dc.date.available2019-01-15T15:52:48Z
dc.date.created2016-12
dc.date.issued2016-12-16
dc.date.submittedDecember 2016
dc.date.updated2019-01-15T15:52:48Z
dc.description.abstractIntraspecific variation in social behavior is common and often dramatic, but little is known about its underlying mechanisms. We use the prairie vole (Microtus ochrogaster) to examine how intraspecific variation in brain and behavior emerges as a result of genetic, epigenetic and environmental variation. Although prairie voles are socially monogamous, they vary in sexual fidelity; faithful prairie voles are described as intra-pair fertilizing (IPF), while unfaithful voles are extra-pair fertilizing (EPF). EPF males have large home-ranges and frequently mate with other females, but do so at the cost of being cuckolded. IPF males however, form small exclusive home-ranges, rarely intrude and are better at mate-guarding. These behavioral differences are predicted by abundance of the vasopressin receptor 1a (V1aR) in the retrosplenial cortex (RSC), a brain region implicated in spatial memory. We find that variation in RSC-V1aR and associated behaviors are predicted by two alternative avpr1a alleles. These “HI” and “LO” alleles are defined by four linked single nucleotide polymorphisms, one of which is a polymorphic CpG site (polyCpG) located within a putative intron enhancer. This polyCpG is weakly linked to several other polyCpGs in the enhancer. Since CpGs are targets for DNA methylation, polyCpGs may cause individual differences in DNA methylation, gene regulation and environmental sensitivity. The unusually high number of polyCpGs within the intron enhancer drives avpr1a genotype differences in CpG density and methylation, which predict avpr1a expression and RSC-V1aR. Examination of avpr1a methylation among wild-caught voles also showed that RSC-V1aR correlated with enhancer methylation, possibly due to genotype differences in enhancer silencing or affinity for transcription factors, but not with promoter methylation. We also found that genotype differences in RSC-V1aR emerge in the first postnatal week, along with changes in enhancer methylation. Before this neurodevelopmental stage, the LO allele, which has more enhancer CpGs, is more sensitive to environmentally-induced changes in RSC-V1aR. These changes however, are not caused by alteration of enhancer methylation, suggesting additional regulatory elements contribute to genotype differences in RSC-V1aR regulation and its environmental sensitivity. Our findings show how genetic and epigenetic variation at a critical gene can shape intraspecific variation in brain and behavior.
dc.description.departmentEcology, Evolution and Behavior
dc.format.mimetypeapplication/pdf
dc.identifierdoi:10.15781/T2222RS6F
dc.identifier.urihttp://hdl.handle.net/2152/72411
dc.language.isoen
dc.subjectPrairie vole
dc.subjectMonogamy
dc.subjectIntraspecific variation
dc.subjectAlternative mating strategies
dc.subjectSexual fidelity
dc.subjectAvpr1a
dc.subjectRetrosplenial cortex
dc.subjectRSC-V1aR
dc.subjectBalancing selection
dc.subjectSingle nucleotide polymorphism (SNP)
dc.subjectCpG polymorphism
dc.subjectEnhancer
dc.subjectDNA methylation
dc.subjectGene by environment interaction (GxE)
dc.titleMolecular regulation of vasopressin receptor among (mostly) monogamous prairie voles
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentEcology, Evolution and Behavior
thesis.degree.disciplineEcology, Evolution and Behavior
thesis.degree.grantorThe University of Texas at Austin
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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