The Epigenetics Revolution

We also know that the DNA methylation systems and histone modification systems often work together. This has created interest in the role of histone-modifying enzymes in the control of honeybee development and activity. When the honeybee genome was sequenced, four histone deacetylase enzymes were identified. This was intriguing because it has been known for some time that royal jelly contains a compound called phenyl butyrate[267]. This very small molecule can inhibit histone deacetylases but it does so rather weakly. In 2011, a group led by Dr Mark Bedford from the MD Anderson Cancer Center in Houston published an intriguing study on another component of royal jelly. One of the other senior authors on this paper was Professor Jean-Pierre Issa, who has been so influential in promoting use of epigenetic drugs for the treatment of cancer.

The researchers analysed a compound found in royal jelly called (E)-10-hydroxy-2-decenoic acid, or 10HDA for short. The structure of this compound is shown in Figure 14.2, along with SAHA, the histone deacetylase inhibitor we saw in Chapter 11 that is licensed for the treatment of cancer.

^{Figure 14.2 The chemical structure of the histone deacetylase inhibitor SAHA and 10HDA, a compound found in royal jelly. C: carbon; H: hydrogen; N: nitrogen; O: oxygen. For simplicity, some carbon atoms have not been explicitly shown, but are present where there is a junction of two lines.}

The two structures aren’t identical by any means, but they do share some similarities. Each has a long chain of carbon atoms (the bit that looks like a crocodile’s back in profile), and the right hand side of each compound also looks fairly similar. Mark Bedford and his colleagues hypothesised that 10HDA might be an inhibitor of histone deacetylases. They performed a number of test tube and cell experiments and showed that this was indeed the case. This means that we now know that one of the major compounds found in royal jelly inhibits a key class of epigenetic enzymes[268].

The forgetful bee and the flexible toolkit

Epigenetics influences more than whether bees develop into workers or queens. Ryszard Maleszka has also shown that DNA methylation is involved in how honeybees process memories. When honeybees find a good source of pollen or nectar, they fly back to the hive and tell the other members of the colony where to head to find this great food supply. This tells us something really important about honeybees; they can remember information. They must be able to, or they wouldn’t be able to tell the other bees where to go for food. Of course, it’s equally important that the bees can forget information and replace it with new data. There’s no point sending your co-workers to the great patch of thistles that were in flower last week, but that have now been eaten by a grazing donkey. The bee needs to forget last week’s thistles and remember the location of this week’s lavender.

It’s actually possible to train honeybees to respond to certain stimuli associated with food. Dr Maleszka and his colleagues showed that when the bees undergo this training, the levels of Dnmt3 protein go up in the parts of the honeybee brains which are important in learning. If the bees are treated with a drug that inhibits the Dnmt3 protein, the compound alters the way the bees retain memories, and also the speed with which memories are lost[269].

Although we know that DNA methylation is important in honeybee memory, we don’t know exactly how this works. This is because it’s not clear yet which genes become methylated when honeybees learn and acquire new memories.

So far, we could be forgiven for thinking that honeybees and higher organisms, including us and our mammalian relatives, all use DNA methylation in the same way. It’s certainly true that changes in DNA methylation are associated with alterations in developmental processes in both humans and honeybees. It’s also true that mammals and honeybees both use DNA methylation in the brain during memory processing.

But oddly enough, honeybees and mammals use DNA methylation in very different ways. A carpenter has a saw in his toolbox and uses it to build a book case. An orthopaedic surgeon has a saw on his operating trolley and uses it to amputate a leg. Sometimes, the same bit of kit can be used in very different ways. Mammals and honeybees both use DNA methylation as a tool, but during the course of evolution they’ve employed it very differently.