How epigenetic modification gives the queen bee her crown

Honey bee colonies are comprised of three kinds of adult bees: workers, drones and a single queen. While all drones are male, the queen and the worker bees are female. Within the female population, only the queen bee is fertile and is thus responsible for laying eggs which are fertilised by drones. Additionally, a queen bee is larger than worker bees and produces pheromones to allow the colony to function. However, worker and queen bees are genetically identical, so how is it possible that they are so fundamentally different? (Figure 1)

The answer lies in epigenetic modification, defined as the alteration in gene function without a change in the DNA sequence. Types of epigenetic regulation include histone modification, DNA methylation and action of noncoding RNA. The honey bee Apis mellifera is amongst the many species that can produce different characteristics of organisms using the same genome. The mechanism by which honey bees do this derives from epigenetic modification resulting from the difference in diet during larval development. 

All larvae feed on royal jelly during the first three days of their development (Figure 2). However, worker larvae will then feed on a diet of honey and pollen, which constitutes worker jelly. In comparison, the queen larva maintains a diet of royal jelly; this is a complex mixture produced by nurse bees and contains water, crude protein, monosaccharides, and fatty acids. Subsequently, the difference in dietary intake provides information to facilitate the correct epigenome which in turn allows correct transcription. Thus, key studies have taken place to investigate the effect of epigenetic marks on the development of bees. 

DNA methyltransferase DNMT3 is responsible for the methylation of DNA and is a repressive mark; a study found that the silencing of DNMT3 resulted in worker larvae developing into queens that had developed ovaries. Consequently, this shows that royal jelly gives information to larvae destined to be queens that can be interpreted to apply the correct epigenome. Additionally, certain histone deacetylase inhibitors have been observed in royal jelly including the compound 10 HDA and phenylbutyrate. Histone acetylation within regions of the genome results in chromatin opening; acetylation is associated with active regions. HDACi activity will inhibit the removal of such acetylation and maintain open regions of DNA. However, note that worker bees are not just a repressed version of queen bees, as they have overexpressed genes of their own to facilitate their specific behaviours. 

On examination of the methylome (see Figure 3), different genes were identified as being hypo- or hyper- methylated within worker vs queen bees. See the table below for a detailed analysis of worker and queen bees on days 3-5 of development.

How exactly the specificity of epigenetic modifications is accomplished is not completely realised. To exemplify this, DNMTs do not have specificity, and thus, there must be an interplay between chromatin modifiers and cellular components to accomplish the correct recruitment of enzymes involved in epigenetic modification. However, it is clear that the epigenomes of workers vs queen bees are decidedly different and thus are the cause of different physiological and behavioural characteristics. 

Written by Isobel Cunningham

Related articles: An introduction to epigenetics / Famine-induced epigenetic changes