It's not you, it's my genes: Sexual fidelity tradeoffs in prairie voles

The adorable, (socially) monogamous prairie vole

Many of you may probably already know the monogamous prairie vole as the yin to the promiscuous montane vole’s yang. Prairie voles are socially monogamous, which is an extremely rare trait among mammals. This trait has made the prairie vole the focus of decades of research on the biology (and neurobiology) of monogamy. The plethora of research has identified two neurotransmitters, vasopressin and oxytocin (aka, the “love hormone”), as key players in the formation and maintenance of the pair bond.
But recent work has shown that not all prairie voles are completely monogamous — some offspring are sired by neighboring males (i.e., not their caregiving father). And the variation in vasopressin receptors (V1aR) in two brain regions, the laterodorsal thalamus (LDThal) and the retrosplenial cortex, predicts which males will wander and mate with extra-pair females. Interestingly these two regions are part of the memory circuit, which led researchers to hypothesize that the males with low V1aR (a vasopressin receptor) in lDThal and RSC have crappy memory, which causes them to repeatedly wander into locations where they previously got their butts kicked by another male. But because they keep wandering into these other territories, they increase their chances of mating with another female!
So a new study published in Science investigated the V1aR gene of prairie voles to see what gene regulatory mechanisms might be responsible for these differences and in what situations selection might favor monogamy versus promiscuity.

Okhovat et al sequenced ~8Kb of the V1aR gene and found four (tightly linked) variants that predicted V1aR abundance in the RSC and one variant that predicted lDThal V1aR* (the called these variants “HI” and “LO” V1aR). They even replicated these HI/LO V1aR findings in voles collected from a new site >100mi away from their other sites (they did this by crossing heterozygous parents to produce offspring that differed in their V1aR genotypes, but had a common genetic background and environment).
They then used a variety of methods to determine the function of these variants. In other words: how do these variants alter the gene regulatory pathway of V1aR? They found that: 1) HI/HI homozygous voles had significantly higher expression of V1aR gene (and levels of the protein) in the RSC, 2) two of the HI variants were located in a putative enhancer (as identified by H3K4me1 ChIP**), and 3) the HI haplotype had fewer CpG sites (the primary site of DNA methylation in mammals) and lower CpG methylation in a putative enhancer, which may lead to increased V1aR expression.
So why are these two genotypes present in the population if LO, bad memory, males get to mate with more females? Well, it’s not that simple: while those LO males are away mating with other females, other LO males are in his house mating with his pair-bonded female. This suggests that LO males might do better in higher-density populations where they have more opportunities to mate with extra-pair females. Indeed, the frequencies of  the HI and LO genotypes exhibited signatures of balancing selection, reflecting the fact that rapid changes in population density may alter the selective pressure on one or the other allele.

Together these data suggest that trade-offs in the fitness consequences of spatial behaviors promote diversity in the social brain.

*Interestingly they found a stronger effect among lab-reared compared to wild-caught voles, which the authors quickly brush off by saying that it “suggests that population structure or developmental environment may influence cortical V1aR.” So, it’s possible that some of their associations were partially driven by the lab-reared animals (for which they had no homozygous “high-V1aR” genotypes; see their Fig. S4). Future work will have to identify whether or not these findings are much stronger in captivity for biological or technical reasons.
** They performed H3K4me1 chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) to identify putative enhancer regions. They did this on a genome-wide scale, but only report the enhancers that fell in the V1aR gene. I wonder if there are other enhancers, possibly farther away, that regulate V1aR? Maybe an ambitious reader wants to download the data and test this out!

Okhovat M, Berrio A, Wallace G, Ophir AG, Phelps SM (2015) Sexual fidelity trade-offs promote regulatory variation in the prairie vole brain. Science, 350, 1371–1374.

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