There are some fundamental aspects of DNA methylation that are quite similar between plants and animals. Plant genomes encode active DNA methyltransferase enzymes, and also proteins that can ‘read’ methylated DNA. Just like primordial germ cells in mammals, certain plant cells can actively remove methylation from DNA. In plants, we even know which enzymes carry out this reaction[288]. One is called DEMETER, after the mother of Persephone in Greek myths. Demeter was the goddess of the harvest and it was because of the deal that she struck with Hades, the god of the Underworld, that we have seasons.
But DNA methylation is also an aspect of epigenetics where there are clear differences in the way plants and higher animals use the same basic system. One of the most obvious differences is that plants don’t just methylate at CpG motifs (cytosine followed by a guanine). Although this is the most common sequence targeted by their DNA methyltransferases, plants will also methylate a cytosine followed by almost any other base[289].
A lot of DNA methylation in plants is focused around non-expressed repetitive elements, just like in mammals. But a big difference becomes apparent when we examine the pattern of DNA methylation in expressed genes. About 5 per cent of expressed plant genes have detectable DNA methylation at their promoters, but over 30 per cent are methylated in the regions that encode amino acids, in the so-called body of the genes. Genes with methylation in the body regions tend to be expressed in a wide range of tissues, and are expressed at moderate to high levels in these tissues[290].
The high levels of DNA methylation at repetitive elements in plants are very similar to the pattern at repetitive elements in the chromatin of higher animals such as mammals. By contrast, the methylation in the bodies of widely expressed genes is much more like that seen in honeybees (which don’t methylate their repetitive elements). This doesn’t mean that plants are some strange epigenetic hybrid of insects and mammals. Instead, it suggests that evolution has a limited set of raw materials, but isn’t too obsessive about how it uses them.
Chapter 16. The Ways Ahead
Prediction is very difficult, especially about the future.
One of the most exciting things about epigenetics is the fact that in some ways it’s very accessible to non-specialists. We can’t all have access to the latest experimental techniques, so not all of us will unravel the chromatin changes that underlie epigenetic events. But all of us can examine the world around us and make predictions. All we need to do is look to see if a phenomenon meets the two most essential criteria in epigenetics. By doing this, we can view the natural world, including humans, in a completely new light. These two criteria are the ones we have returned to over and over again throughout this book. A phenomenon is likely to be influenced by epigenetic alterations in DNA and its accompanying proteins if one or both of the following conditions are met:
Two things are genetically identical, but phenotypically variable;
An organism continues to be influenced by an event long after this initiating event has occurred.
We always have to apply a common sense filter, of course. If someone loses their leg in a motorbike accident, the fact that they are still minus a leg twenty years later doesn’t mean that we can invoke an epigenetic mechanism. On the other hand, that person may continue to have the sensation that they have both legs. This phantom limb syndrome might well be influenced by programmed gene expression patterns in the central nervous system that are maintained in part by epigenetic modifications.
We are sometimes so overwhelmed by the technologies used in modern biology that we forget how much we can learn just by looking thoughtfully. For example, we don’t always need sophisticated laboratory equipment to determine if two phenotypically different things are genetically identical. Here are a couple of examples with which we are all familiar. Maggots turn into flies and caterpillars turn into butterflies. An individual maggot and the adult fly into which it finally develops must have the same genetic code. It’s not as if a maggot can request a new genome as it metamorphoses. So, the maggot and the fly use the same genome in completely different ways. The painted lady caterpillar has interesting spikes all over its body and is fairly dull in colour. Like a maggot, it has no wings. The painted lady butterfly is a beautiful creature, with enormous wings coloured black and vivid orange, and it has no big spikes on its body. Once again, an individual caterpillar and the butterfly into which it develops must have the exact same DNA script. But the final productions from these scripts differ enormously. We can hypothesise that this is likely to involve epigenetic events.
The stoat Mustela ermine is found in Europe and North America. It’s an athletic little predator in the weasel family, and in summer the fur on its back is a warm brown and its front is a creamy white. In cold climates its coat turns almost completely white all over in the winter, except for the tip of its tail, which remains black. With the arrival of spring, the stoat reverts to its summer colours. We know that there are hormonal effects that are required for this seasonal change in coat colour. It’s pretty reasonable to hypothesise that these influence the relevant expression of coat colour genes by methods which include epigenetic modifications to chromatin.
In mammals, there’s usually a clear genetic reason why males are males and females are females. A functional Y chromosome leads to the male phenotype. In lots of reptile species, including crocodiles and alligators, the two sexes are genetically identical. You can’t predict the sex of a crocodile from its chromosomes. The sex of a crocodile or an alligator depends on the temperature during critical stages in the development of the egg – the same blueprint can be used to create either a male or a female croc[291]. We know that hormonal signalling is involved in this process. There hasn’t been much investigation of whether or not epigenetic modifications play a role in establishing or stabilising the gender-specific patterns of gene expression, but it seems likely.
Understanding the mechanisms of sex determination in crocodiles and their relatives may become a rather important conservation issue in the near future. The global shift in temperatures due to climate change could have adverse consequences for these reptiles, if the populations become very skewed in favour of one sex over another. Some authors have even speculated that such an effect may have contributed to the extinction of the dinosaurs[292].
The ideas above are quite straightforward, easily testable hypotheses. We can generate a lot more like these by simple observation. It’s a lot riskier to make broad claims about what other more general developments we might expect to see in epigenetic research. The field is still young, and moving in all sorts of unexpected directions. But let’s render ourselves hostages to fortune, and make a few predictions anyway.
We’ll start with a fairly specific one. By 2016 at least one Nobel Prize for Physiology or Medicine will have been awarded to some leading workers in this field. The question is to whom, because there are plenty of worthy candidates.
For many people in the field it’s extraordinary that this hasn’t yet been awarded to Mary Lyon for her remarkably prescient work on X inactivation. Although her key papers that laid the conceptual framework for X inactivation didn’t contain much original experimental data, this is also true of James Watson and Francis Crick’s original paper on the structure of DNA[293]. It’s always tempting to speculate the lack of a Nobel Prize might be down to gender, but that’s partly because of a myth that has grown up around Rosalind Franklin. She was the X-ray crystallographer whose data were essential for the development of the Watson-Crick model of DNA. When the Nobel Prize was awarded to Watson and Crick in 1962 it was also awarded to Rosalind Franklin’s lab head, Professor Maurice Wilkins from Kings College, London. But Rosalind Franklin didn’t miss out on the prize because she was a woman. She missed out because she had, tragically, died of ovarian cancer at the age of 37, and the Nobel Prize is never awarded posthumously.