Genome-wide effects of social status on DNA methylation in the brain of a cichlid fish, Astatotilapia burtoni

BackgroundSuccessful social behavior requires integration of information about the environment, internal physiology, and past experience in real-time. The molecular substrates of this integration are poorly understood, but are likely involved in modulating neural plasticity and gene regulation. Astatotilapia burtoni is a species of cichlid fish with a dynamic social hierarchy. A male’s status can shift rapidly depending on the social environment, causing swift behavioral modifications that trigger a cascade of changes in gene transcription, the brain, and the reproductive system. These changes can be permanent but are also reversible, depending on the environment, implying the involvement of a robust yet flexible mechanism that regulates biological plasticity based on environmental and internal conditions. One candidate mechanism is DNA methylation, which has been linked to social behavior in many species, including A. burtoni. But, the extent of it’s effects after A. burtoni social change were previously unknown.ResultsWe performed the first genome-wide search for DNA methylation patterns associated with social status in the brains of male A. burtoni, identifying hundreds of Differentially Methylated genomic Regions (DMRs) in dominant versus non-dominant fish. Most DMRs were inside genes supporting neural development, synapse function, and other processes relevant to neural plasticity, and DMRs could affect gene expression in multiple ways. DMR genes included neurotransmitter receptors, voltage-gated ion channels, cell adhesion and intracellular signaling molecules, axon guidance factors and their receptors, and different types of growth factors. DMR genes were more likely to be transcription factors, have a duplicate elsewhere in the genome, have an anti-sense lncRNA, contain more transposable elements, and have more splice variants than other genes. Dozens of genes had multiple DMRs that were often seemingly positioned to regulate specific splice variants.ConclusionsOur results revealed genome-wide effects of A. burtoni social status on DNA methylation in the brain and strongly suggest a role for methylation in modulating plasticity across multiple biological levels. They also suggest many novel hypotheses to address in mechanistic follow-up studies, and will be a rich resource for identifying the relationships between behavioral, neural, and transcriptional plasticity in the context of social status.