The Epigenetics Revolution

All these data suggested that something in the male chromosomes pushes the developmental programme in favour of the placenta, whereas a maternally-derived genome has less of a drive towards the placenta, and more towards the embryo itself. How is this consistent with the conflict or evolutionary imperative laid out earlier in this chapter? Well, the placenta is the portal for taking nutrients out of the mother and transferring them into the foetus. The paternally-derived chromosomes promote placental development, and thereby create mechanisms for diverting as much nutrition as possible from the mother’s bloodstream. The maternal chromosomes act in the opposite way, and a finely poised stalemate develops in normal pregnancies.

One obvious question is whether all the chromosomes are important for these effects. Bruce Cattanach used complex genetic experiments on mice to investigate this. The mice contained chromosomes that had been rearranged in different ways. The simplest way to explain this is that each mouse had the right amount of chromosomes, but they’d been ‘stuck together’ in unusual ways. He was able to create mice which had precise abnormalities in the inheritance of their chromosomes. For example, he could create mice which inherited both copies of a specific chromosome from just one parent.

The first experiments he reported were using mouse chromosome 11. For all the other pairs of chromosomes, the mice inherited one of each pair maternally, and one paternally. But for chromosome 11, Bruce Cattanach created mice that had inherited two copies from their mother and none from their father, or vice versa. Figure 8.1 represents the results[65].

^{Figure 8.1 Bruce Cattanach created genetically modified mice, in which he could control how they inherited a particular region of chromosome 11. The middle mouse inherited one copy from each parent. Mice which inherited both copies from their mother were smaller than this normal mouse. In contrast, mice which inherited both copies from their father were larger than normal.}

Once again this is consistent with the idea that there are factors in the paternal chromosomes that push towards development of larger offspring. Factors in the maternal chromosomes either act in the ‘opposite direction’ or are broadly neutral.

As we explored in the last chapter, these factors are epigenetic, not genetic. In the example above, let’s assume that the parents came from the same inbred mouse strain, so were genetically identical. If you sequenced both copies of chromosome 11 in any of the three types of offspring, they would be exactly the same. They would contain the same millions of A, C, G and T base-pairs, in the same order. But the two copies of chromosome 11 do clearly behave differently at a functional level, as shown by the different sizes of the different types of mice. Therefore there must be epigenetic differences between the maternal and paternal copies of chromosome 11.

Sex discrimination

Because the two copies of the chromosome behave differently depending on their parent-of-origin, chromosome 11 is known as an imprinted chromosome. It has been imprinted with information about its origins. As our understanding of genetics has improved we’ve realised that only certain stretches of chromosome 11 are imprinted. There are large regions where it doesn’t matter at all which parent donated which chromosome, and the regions from the two parents are functionally equivalent. There are also entire chromosomes that are not imprinted.

So far, we’ve described imprinting in mainly phenomenological terms. Imprinted regions are stretches of the genome where we can detect parent-of-origin effects in offspring. But how do these regions carry this effect? In imprinted regions, certain genes are switched on or switched off, depending on how they were inherited. In the chromosome 11 example above, genes associated with placental growth are switched on and are very active in the copy of the chromosome inherited from the father. This carries risks of nutrient depletion for the mother who is carrying the foetus, and a compensatory mechanism has evolved. The copies of these same genes on the maternal chromosome tend to be switched off, and this limits the placental growth. Alternatively, there may be other genes that counterbalance the effects of the paternal genes, and these counter-balancing genes may be expressed mainly from the maternal chromosome.