DNA methylation, epialleles and gene regulation: Insights from the honey bee

Abstract

The development of a multicellular organism is dependent upon interactions between the underlying genetic sequence, epigenomic processes and environmental cues. These interactions are complex, and understanding the exact role that each plays in directing transcription remains difficult. One of the more well studied epigenomic modifications, cytosine DNA methylation, plays a fundamental role in modulating gene activity. This modification has primarily been associated with gene repression, but recent evidence has highlighted that DNA methylation also correlates with gene activation, and that variation in methylation patterning occurs across species. In the honey bee DNA methylation predominately occurs intragenically, and is associated with active transcription. The discovery that DNA methylation is critical to caste determination in the bee and additional correlations between DNA methylation, behaviour and phenotype, has made the honey bee an interesting model organism from which we can gain insight into the role of DNA methylation. Whilst it has been shown extensively in plants and mammals that DNA methylation patterns are frequently dependent on genotype, few studies of the honey bee have interpreted differential DNA methylation patterns in the context of the underlying genetic sequence. Here, we show that differences in the underlying genetic sequence correlate with differential methylation of the gene coding for lysosomal α-mannosidase (LAM), demonstrating that several LAM epialleles exist in the honey bee population. These epialleles correlate with context-dependent transcriptional changes, with significant effects on LAM expression observed during larval development. To understand how such changes might affect larval growth and phenotype we used a knockdown approach, inhibiting LAM activity during early larval stages using the indolizidine alkaloid swainsonine. We show that such treatment causes sub-lethal effects during larval and pupal stages, and causes loco-like symptoms and death in newly emerged bees. Our findings suggest that LAM function in the honey bee is conserved, and we propose that the LAM epialleles might affect larval metabolism and growth. By influencing metabolism in the bee the LAM epialleles could generate substantial variation in complex traits, which would be beneficial to a colony whose stability is dependent upon high levels of phenotypic variation. Show more