The Epigenetics Revolution

The answer has its origin about 150 million years ago, when the XY system of sex determination in placental mammals first developed. The X and Y chromosomes are probably descendants of autosomes. The Y chromosome has changed dramatically, the X chromosome much less so[120]. However, both retain shadows of their autosomal past. There are regions on both the X and the Y called pseudoautosomal regions. The genes in these regions are found on both the X and the Y chromosome, just in the same way as pairs of autosomes have the same genes in the same positions, one inherited from each parent.

When an X chromosome inactivates, these pseudoautosomal regions are spared. This means that, unlike most X-linked genes, those in the pseudoautosomal regions don’t get switched off. Consequently, normal cells potentially express two copies of these genes in all cells. The two copies are expressed either from the two X chromosomes in a normal female or from the X and the Y in a normal male.

But in Turner’s syndrome, the affected female only has one X chromosome, so she expresses only one copy of the genes in the pseudoautosomal region, half as much as normal. In Trisomy X, on the other hand, there are three copies of the genes in the pseudoautosomal regions. As a result, the cells in an affected region will produce proteins from these genes at 50 per cent above the normal level.

One of the genes in the X chromosome pseudoautosomal regions is called SHOX. Patients with mutations in this gene have short stature. It is likely that this is also why patients with Turner’s syndrome tend to be short – they don’t produce enough SHOX protein in their cells. By contrast, patients with Trisomy X are likely to produce 50 per cent more SHOX protein than normal, which is probably why they tend to be tall[121].

It’s not just humans who have trisomies of the sex chromosomes. One day you may be happily amazing your friends with your confident statement that their tortoiseshell cat is female when they deflate you by telling you that their pet has been sexed by the vet and is actually a Tom. At this point, smile smugly and then say ‘Oh, in that case he’s karyotypically abnormal. He has an XXY karyotype, rather than XY’. And if you’re feeling particularly mean, you can tell them that Tom is infertile. That should shut them up.

Chapter 10. The Message is Not the Medium

Science commits suicide when it adopts a creed.

Thomas Henry Huxley

One of the most influential books on the philosophy of science is Thomas Kuhn’s The Structure of Scientific Revolutions, published in 1962. One of the claims in Kuhn’s book is that science does not proceed in an orderly, linear and polite fashion, with all new findings viewed in a completely unbiased way. Instead, there is a prevailing theory which dominates a field. When new conflicting data are generated, the theory doesn’t immediately topple. It may get tweaked slightly, but scientists can and often do continue to believe in a theory long after there is sufficient evidence to discount it.

We can visualise the theory as a shed, and the new conflicting piece of data as an oddly shaped bit of builder’s rubble that has been cemented onto the roof. Now, we can probably continue cementing bits of rubble onto the roof for quite some time, but eventually there will come a point when the shed collapses under the sheer weight of odd bits of masonry. In science, this is when a new theory develops, and all those bits of masonry are used to build the foundations of a new shed.

Kuhn described this collapse-and-rebuild as the paradigm shift, introducing the phrase that has now become such a cliché in the high-end media world. The paradigm shift isn’t just based on pure rationality. It involves emotional and sociological changes in the psyches of the upholders of the prevailing theory. Many years before Thomas Kuhn’s book, the great German scientist Max Planck, winner of the 1918 Nobel Prize for Physics, put this rather more succinctly when he wrote that, ‘Scientific theories don’t change because old scientists change their minds; they change because old scientists die[122].’

We are in the middle of just such a paradigm shift in biology.

In 1965, the Nobel Prize in Physiology or Medicine was awarded to François Jacob, André Lwoff and Jacques Monod ‘for their discoveries concerning genetic control of enzyme and virus synthesis’. Included in this work was the discovery of messenger RNA (mRNA), which we first met in Chapter 3. mRNA is the relatively short-lived molecule that transfers the information from our chromosomal DNA and acts as the intermediate template for the production of proteins.