Epigenetics: It's not all about DNA

Epigenetics can be defined as any change in gene expression which has been caused by means other than changes to the underlying DNA. These epigenetic changes remain during subsequent cell divisions and can be passed down through subsequent generations. It is a burgeoning scientific field that is overturning much of what we thought we knew about inheritance.

DNA is still of course the big player, but it is not the only mechanism of inheritance in town. And the more that scientists look at epigenetic changes to genes, the more they realise that there is a lot of it going on, much more than previously thought, and that epigenetic changes also contribute to some disease processes.

There is plenty of evidence that demonstrates how epigenetic changes (and not changes in the DNA of a gene) have been passed on to the next generation. For example:

• Drosophila melanogaster - the fruit fly has white eyes. Embryos develop in temperatures of 25 degrees Celsius. However, in an experiment this was raised to 37 degrees Celsius and the flies developed red eyes. When these were crossed again the offspring were partly red-eyed. Scientists from ETH, the Swiss Federal Institute of Technology were able to show that the DNA of the gene responsible for eye colour was no different for red or white-eyed fruit flies. So the heritable changes had not taken place in the DNA.

• Fruit flies again! - When fruit flies were exposed to certain chemicals, 13 generations of their descendants had bristly outgrowths on their eyes - these were not caused by any changes in the DNA, rather the changes were by epigenetic means (Jablonka et al. Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution. The Quarterly Review of Biology, 2009; 84 (2): 131 DOI: 10.1086/598822).

• Twin studies - monozygotic, or identical twins are just that - identical - they have identical DNA. However, during their lifetimes there are differences in their phenotypes, such as susceptibility to some diseases. One possible explanation could be changes in the epigentic factors that affect genes and modify gene expression. Scientists at the University of Washington, Seattle have shown that in monozygotic twins some epigenetic factors are identical in early life, but they acquire differences as time passes. It could be that these differences modify genes in such a way as to create the phenotype differences that have been observed.

There are several epigenetic ways that a gene can be modified, that is having its expression altered without changes to its DNA. Two of the most widely studied are DNA methylation and histone modification.

1) DNA methylation - where methyl groups latch onto parts of a DNA sequence and can switch a gene on or off.

2) Histone modification - DNA winds around histone proteins for compaction and gene regulation, but certain epigenetic factors can bind to the histones which affects the extent to which DNA winds around the protein. This effects gene expression.

It was Jean Baptise Lamarck who in the 18th century suggested that evolution in part was driven by the inheritance of acquired traits. His ideas fell out of favour when Darwin came along, and 20th century DNA discoveries. However, in the light of epigenetic findings, they don't appear to be so wide of the mark after all.