The Epigenetics Revolution

When mammals methylate DNA, they usually methylate the promoter regions of genes, and not the parts that code for amino acids. Mammals also methylate repetitive DNA elements and transposons, as we saw in Emma Whitelaw’s work in Chapter 5. DNA methylation in mammals tends to be associated with switching off gene expression and shutting down dangerous elements like transposons that might otherwise cause problems in our genomes.

Honeybees use DNA methylation in a completely different way. They don’t methylate repetitive regions or transposons, so they presumably have other ways of controlling these potentially troublesome elements. They methylate CpG motifs in the stretches of genes that encode amino acids, rather than in the promoter regions of genes. Honeybees don’t use DNA methylation to switch off genes. In honeybees, DNA methylation is found on genes that are expressed in all tissues, and also on genes that tend to be expressed by many different insect species. DNA methylation acts as a fine-tuning mechanism in honeybee tissues. It modulates the activity of genes, turning the volume slightly up or down, rather than acting as an on-off switch[270]. Patterns of DNA methylation are also strongly correlated with control of mRNA splicing in honeybee tissues. However, we don’t yet know how this epigenetic modification actually influences the way in which a message is processed[271].

We’re really only just beginning to unravel the subtleties of epigenetic regulation in honeybees. For example, there are 10,000,000 CpG sites in the honeybee genome, but less than 1 per cent of these are methylated in any given tissue. Unfortunately, this low degree of methylation makes analysing the effects of this epigenetic modification very challenging. The effects of Dnmt3 knockdown show that DNA methylation is very important in honeybee development. But, given that DNA methylation is a fine-tuning mechanism in this species, it’s likely that Dnmt3 knockdown results in a number of individually minor changes in a relatively large number of genes, rather than dramatic changes in a few. These types of subtle alterations are the most difficult to analyse, and to investigate experimentally.

Honeybees aren’t the only insect species that has developed a complex society with differing forms and functions for genetically identical individuals. This model has evolved independently several times, including in different species of wasps, termites, bees and ants. We don’t yet know if the same epigenetic processes are used in all these cases. Shelley Berger from the University of Pennsylvania, whose work on ageing we encountered in Chapter 13, is involved in a large collaboration focusing on ant genetics and epigenetics. This work has already shown that at least two species of ants also can methylate the DNA in their genomes. The expression of different epigenetic enzymes varies between different social groups in the colonies[272]. These data tentatively suggest that epigenetic control of colony members may prove to be a mechanism that has evolved more than once in the social insects.

For now, however, most interest in the world outside epigenetics labs focuses on royal jelly, as this has a long history as a health supplement. It’s worth pointing out that there’s very little hard evidence to support this having any major effects in humans. The 10HDA, that Mark Bedford and his colleagues showed was a histone deacetylase inhibitor, can affect the growth of blood vessel cells[273]. Theoretically, this could be useful in cancer, as tumours rely on a good blood supply for continuing growth. However, we’re a very long way from showing that royal jelly can really fight off cancer, or aid human health in any other way. If there’s one thing we do already know, it’s that bees and humans are not the same epigenetically. Which is just as well, unless you’re a really big fan of the monarchy …

Chapter 15. The Green Revolution

To see a world in a Grain of Sand,

And a Heaven in a Wild Flower,

Hold Infinity in the palm of your hand,

And eternity in an hour.

William Blake

Probably all of us are familiar with the guessing game ‘animal, vegetable or mineral’. The implicit assumption in the name of this game is that plants and animals are completely different from one another. True, they are both living organisms, but that’s where we feel the similarity ends. We may be able to get on board with the idea that somewhere back in the murky evolutionary past, humans and microscopic worms have a shared ancestor. But how often do we ever wonder about the biological heritage we share with plants? When do we ever think of carnations as our cousins?