Gene regulatory evolution and the origin of complex behaviors in the prairie vole, Microtus ochrogaster

Understanding variation in form and behavior within and among species requires mapping genotypes to phenotypes. Much of this variation depends on differences in regulatory DNA scattered throughout the genome; in the context of behavior, these regulatory sequences govern gene expression in regions of the brain that shape behavior. Surprisingly few studies have characterized the regulatory changes that underlie the adaptive evolution of brain and behavior. In my PhD dissertation project, I investigated the adaptive role of gene regulation in the evolution of pair-bonding and sexual fidelity in the prairie voles, Microtus ochrogaster. Expression of Avpr1a in the ventral pallidum plays a critical role in the origin and evolution of pair-bonding in these monogamous voles. In Chapter 1, I have applied phylogenetic and population genetic methods to find signatures of selection in functional elements in the prairie vole genome. I identified a regulatory element of the Avpr1a locus that is under positive selection, this sequence coincides with the origins of expression of this gene in a reward region, the ventral pallidum. Then, I tested its causality using transgenic mouse enhancer assays. I found that transgenic mice expressing a reporter under the control of this prairie vole enhancer were able to drive expression in the ventral pallidum, but expression was sensitive to insertion site. Interestingly, this gene also shows profound differences between individuals. In Chapter 2, I applied population genomic tools to demonstrate that this locus shows signatures of balancing selection in a polymorphic enhancer that predicts expression in a spatial memory circuit. I found that alleles that predict aspects of space use and sexual fidelity are strongly linked to each other. Moreover, I show evidence that the evolution of this regulatory element seems to be mediated by a mix of balancing, epistatic and density-dependent selection. In Chapter 3, I performed RNA-sequencing experiments to analyze monogamy-related genomic changes in the brain. I found massive changes in gene expression of prairie voles in contrast to promiscuous meadow voles, despite their gene expression modules are very well preserved. Moreover, neuroplasticity –a neural process involved with learning— was strongly activated in prairie but not it meadow vole brains. Overall, the results of these experiments reveal the potential for gene regulation to drive the adaptive evolution of complex behaviors.