The Epigenetics Revolution

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.

Bruce Cattanach is a scientist we have met before in these pages. In addition to his work on parent-of-origin effects, he also performed some of the key early experimental studies on the molecular mechanisms behind X inactivation[294]. He would be considered a worthy co-recipient with Mary Lyon by most researchers. Mary Lyon and Bruce Cattanach performed much of their seminal research in the 1960s and are long-since retired. However, Robert Edwards, the pioneer of in vitro fertilisation, received the 2010 Nobel Prize in his mid-eighties, so there is still time and a little hope left for Professors Lyon and Cattanach.

The work of John Gurdon and Shinya Yamanaka on cellular reprogramming has revolutionised our understanding of how cell fate is controlled, and they must be hot favourites for a trip to Stockholm soon. A slightly less mainstream but appealing combination would be Azim Surani and Emma Whitelaw. Together their work has been seminal in demonstrating not only how the epigenome is usually reset in sexual reproduction, but also how this process is occasionally subverted to allow the inheritance of acquired characteristics. David Allis has led the field in the study of epigenetic modifications to histones, and must also be an attractive choice, possibly in combination with some of the leading lights in DNA methylation, especially Adrian Bird and Peter Jones.