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
