Rodentology: epigenetics of behavior
Even identical twins, who share all of their genes, differ slightly in their behavior even when they are in the same environment. Besides sequence-level differences, genomes differ in a number of other ways that effect gene expression. This is your epigenome.Alter et al. tie large-scale differences in gene expression level to open field behavior in mice. Being handled after birth has long been known to influence anxiety levels and behavior and goes back to Seymour Levine's work with rats in the 1950s. Rodents that are handled as infants end up being more bold.
Despite sharing the same genes, identical twins demonstrate substantial variability in behavioral traits and in their risk for disease. Epigenetic factors–DNA and chromatin modifications that affect levels of gene expression without affecting the DNA sequence–are thought to be important in establishing this variability. Epigenetically-mediated differences in the levels of gene expression that are associated with individual variability traditionally are thought to occur only in a gene-specific manner. We challenge this idea by exploring the large-scale organizational patterns of gene expression in an epigenetic model of behavioral variability.To study the effects of epigenetic influences on behavioral variability, we examine gene expression in genetically identical mice. Using a novel approach to microarray analysis, we show that variability in the large-scale organization of gene expression levels, rather than differences in the expression levels of specific genes, is associated with individual differences in behavior. Specifically, increased activity in the open field is associated with increased variance of log-transformed measures of gene expression in the hippocampus, a brain region involved in open field activity.
The only thing I don't quite follow in this study are their quality control measures. One problem with these experiments is that large differences you see between microarrays can be due to how much fluorescent dye you happened to squirt on them. You then attempt to control for this variability. Of course the authors make a number of references to the MicroArray Quality Control Project, which means everything is OK, right?
Alter MD, Rubin DB, Ramsey K, Halpern R, Stephan DA, et al. (2008) Variation in the Large-Scale Organization of Gene Expression Levels in the Hippocampus Relates to Stable Epigenetic Variability in Behavior. PLoS ONE 3(10): e3344. doi:10.1371/journal.pone.0003344
