Wiring the Brain: The Trouble with Epigenetics (Part 1)

You keep using that word. I do not think it means what you think it means. The insightful Inigo Montoya.

Epigenetics is a word that seems to have caught the public imagination. This is especially true among those, both in science and without, who decry what they see as genetic determinism or at least an overly genocentric point of view. Our genes are not our fate, because epigenetics! Such-and-such disorder is not really genetic, because epigenetics! Acquired characteristics can be inherited, because epigenetics!

This molecular biology definition has really only a loose relationship to Waddingtons usage. It is obviously true that molecular mechanisms of gene regulation effect (as in mediate) the development of an organism. That is what cellular differentiation and coordinated organismal development entail. Genes are turned on, genes are turned off. Epigenetic mechanisms make the profiles of gene expression that define a particular cell type more stable, with different sets of genes held in active or inactive chromatin conformations. These two usages thus relate to very different levels one refers to the profile of gene expression of individual cell types and the other to the emergence of the phenotype of the organism.

Now, clearly, the phenotype of an organism depends largely (though by no means completely) on the profile of gene expression of its constituent cells. And there are indeed a number of examples where the behavioural phenotype of an organism has been linked to the epigenetic state of particular genes in cells in particular brain regions. Importantly, such mechanisms may provide one means whereby environmental factors or particular experiences can have long-lasting effects on an organism, by changing patterns of gene expression in particular cells in a stable manner.

Based on these kinds of examples, epigenetics has become quite a buzz-word in the fields of psychiatric and behavioural genetics, as if it provides a general molecular mechanism for all the non-genetic factors that influence an individuals phenotype.

The fact that environmental factors or extreme experiences can influence an organisms phenotype is not news. In specific cases like those described above, the effects of such factors may indeed be mediated by molecular epigenetic mechanisms. But heres the important thing even though epigenetic mechanisms may be involved in maintaining some stable traits over the lifetime of the animal, they are just that: mechanisms. Not causes. Epigenetics is not a source of variance, it is part of the mechanism whereby certain environmental factors or experiences have their effects. Furthermore, these few examples do not imply that this mechanism is involved in mediating the effects of non-genetic sources of variance more generally.

So, while epigenetic mechanisms may indeed play a role in the stable expression of certain behavioural tendencies (at least in rodents), it remains unclear how general this phenomenon is. In any case, there is no reason to think of epigenetics as a source or cause of phenotypic variance at the level of the organism. And here is a plea: if you are tempted to use the term epigenetic, make it clear which meaning you intend. If you simply mean non-genetic, there is a more precise term for this: non-genetic.

In part 2, I consider a more egregious trend emerging in the literature of late the idea that transgenerational epigenetic inheritance can provide a mechanism of heredity that explains the so-called missing heritability of psychiatric disorders. (It cant).

Continued here:
Wiring the Brain: The Trouble with Epigenetics (Part 1)