The Epigenetics Revolution

Histone modifications also allow cells to ‘try out’ particular patterns of gene expression, especially during development. Genes become temporarily inactivated when repressive histone modifications (those which drive gene expression down) are established on the histones near those genes. If there is an advantage to the cell in those genes being switched off, the histone modifications may last long enough to lead to DNA methylation. The histone modifications attract reader proteins that build up complexes of other proteins on the nucleosome. In some cases the complexes may include DNMT3A or DNMT3B, two of the enzymes that deposit methyl groups on CpG DNA motifs. Under these circumstances, the DNMT3A or 3B can ‘reach across’ from the complex on the histone and methylate the adjacent DNA. If enough DNA methylation takes place, expression of the gene will shut down. In extreme circumstances the whole chromosome region may become hyper-compacted and inactivated for multiple cell divisions, or for decades in a non-dividing cell like a neuron.

Why have organisms evolved such complex patterns of histone modifications to regulate gene expression? The systems seem particularly complex when you contrast them with the fairly all-or-nothing effects of DNA methylation. One of the reasons is probably because the complexity allows sophisticated fine-tuning of gene expression. Because of this, cells and organisms can adapt their gene expression appropriately in response to changes in their environment, such as availability of nutrients or exposure to viruses. But as we shall see in the next chapter, this fine-tuning can result in some very strange consequences indeed.

Chapter 5. Why Aren’t Identical Twins Actually Identical?

There are two things in life for which we are never prepared: twins.

Josh Billings

Identical twins have been a source of fascination in human cultures for millennia, and this fascination continues right into the present day. Just taking Western European literature as one source, we can find the identical twins Menaechmus and Sosicles in a work of Plautus from around 200 B.C.; the re-working of the same story by Shakespeare in The Comedy of Errors, written around 1590; Tweedledum and Tweedledee in Lewis Carroll’s Through the Looking-Glass, and What Alice Found There written in 1871; right up to the Weasley twins in the Harry Potter novels of J. K. Rowling. There is something inherently intriguing about two people who seem exactly the same as one another.

But there is something that interests all of us even more than the extraordinary similarities of identical twins, and that is when we can see their differences. It’s a device that’s been repeatedly used in the arts, from Frederic and Hugo in Jean Anhouil’s Ring around the Moon to Beverley and Elliott Mantle in David Cronenberg’s Dead Ringers. Taking this to its extreme you could even cite Dr Jekyll and his alter ego Mr Hyde, the ultimate ‘evil twin’. The differences between identical twins have certainly captured the imaginations of creative people from all branches of the arts, but they have also completely captivated the world of science.

The scientific term for identical twins is monozygotic (MZ) twins. They were both derived from the same single-cell zygote formed from the fusion of one egg and one sperm. In the case of MZ twins the inner cell mass of the blastocyst split into two during the early cell divisions, like slicing a doughnut in half, and gave rise to two embryos. And these embryos are genetically identical.

This splitting of the inner cell mass to form two separate embryos is generally considered a random event. This is consistent with the frequency of MZ twins being pretty much the same throughout all human populations, and with the fact that identical twins don’t run in families. We tend to think of MZ twins as being very rare but this isn’t really the case. About one in every 250 full-term pregnancies results in the birth of a pair of MZ twins, and there are around ten million pairs of identical twins around the world today.

MZ twins are particularly fascinating because they help us to determine the degree to which genetics is the driving force for life events such as particular illnesses. They basically allow us to explore mathematically the link between the sequences of our genes (genotype) and what we are like (phenotype), be this in terms of height, health, freckles or anything else we would like to measure. This is done by calculating how often both twins in a pair present with the same disease. The technical term for this is the concordance rate.