Elegant experiment

In an elegant experiment published in Science in March this year, Maleszka’s team decided to see what would happen if one of those methyltransferase genes, in this case Dmnt3, which is the enzyme that adds new methyl tags to DNA strands and is a key driver of epigenetic global reprogramming, was silenced in newly emerged larvae.

“The larvae only have a very short time when they are responsive to the royal jelly,” Maleszka says. “It is up to about 48, maybe 60 hours, and then after that there is no way of changing the development trajectory. So we silenced the gene at the moment they were born to see what happened.”

What happened was that about 80 per cent of the larvae developed as queens, with fully developed ovaries, a situation completely reversed in the control group, where about 80 per cent emerged as sterile workers.

The experiment directly mimicked what would happen if the larvae were fed exclusively on royal jelly, suggesting that DNA methylation in bees is used for storing epigenetic information. It also seems that the use of that information can be differentially altered by what the bees eat, their nutritional input. As the team wrote in the paper, the study suggests that the flexibility of epigenetic modifications underpins profound shifts in developmental fates, with massive implications for reproductive and behavioural status.

Maleszka believes the honey bee is a beautiful system to study not only the functional overlap of DNA methylation in mammals and invertebrates, but also to try to understand the nutritional and environmental basis of epigenetic re-programming.

“I am assuming, and I think I’m right, that mechanistically, at the level of biochemistry, it is very similar. It has been shown already in other systems that you have the fundamental biochemical similarity in different species and then you have other levels of complexity that make the difference. But at the very basic molecular level I think we will see enormous overlap with the bees and mammals, and that makes the bee very useful.

“It is probably the only system where we know exactly the nutritional ingredients used for global genomic reprogramming and we can use this information for manipulating development and to study all of those events from the moment the process is triggered and development is changed.”