Social Status, Epigenetic Variation, and Complex Phenotypes: How Dominance Hierarchies Affect Plastic DNA Methylation in the Yellowstone Gray Wolf (Canis lupus)

Abstract

In mammals social environment, vis-à-vis gene expression regulation, has been shown to impact both general health in the short term and evolutionarily significant factors, such as fertility, in the long term. This phenomenon is most readily observable in species that organize into strict dominance hierarchies, so much so that in some species differential gene expression levels are so pronounced as to be associative and predictive of social rank. The wild Yellowstone Gray Wolves (Canis lupus) was an ideal subject species in which to explore this phenomenon, being a cooperatively breeding species in which each sex has its own social hierarchy. Lacking the ability to create gene expression profiles I instead used CpG island (CpGI) methylation, which is not only a mechanism of environmental and age based epigenetic change but also the most prolific mode of epigenetic modification in vertebrates, as a proxy for gene expression. I tested for association in 35 Gray Wolves (19 males and 16 females) between blood and tissue DNA methylation profiles and social rank. Through this I identified 489236 unique differentially methylated CpGs (DM-CpGs), 155 of which possessed statistically significant absolute differences in methylation greater than 25%. 119 CpGs were hypermethylated and 37 were hypo-methylated. While none of these DM-CpGs, or their associated CpGI, were associated with domesticated canine (Canis familiaris) genes, until an annotated Gray Wolf gene list is made available the question of their genic relevance, or lack thereof, cannot be definitively decided. In summary, my results, while not conclusive, further reinforce the idea that gene expression is plastic and linked with social environment, specifically rank, in cooperatively breeding, social hierarchical, mammals. Furthermore, the 155 DM-CpGs/CpGIs I identified can be used as a candidate DNA locus list for future research in the vein of social context and plastic gene expression.