The “epi” thingy – new genetics

You are what you eat, right? This is the notion that to be fit and healthy you need to eat foods that are good for you. If you eat too much you can get fat. If you drink too little fluids you might get kidney stones. If you consume too much alcohol you can destroy your liver. On the contrary, consuming omega-3 fatty acids can improve your brain function and fibre can improve your gut function. Sounds about right that all such external inputs can influence your genetic potential, but not the genes themselves, doesn’t it? Remember genotype (what we inherit from our parents) and phenotype (the expression of the genotype as influenced by environmental factors). This is typical Mendelian theory.

But now we have to take this one step further. Your children might become what you eat and even their children and beyond can be influenced by your dietary pattern through genetic changes. Is this heresy or what? The genotype is not supposed to be influenced by environmental factors. Environmental factors, which change the characteristics of an individual and are then passed on to its offspring, do not really fit into Darwin’s theory of evolution. According to his theory, evolution is the result of the population and not the single individual.

The reason lies in epigenetics, the study of how changes in your environment and your own lifestyle choices can affect how your genes are expressed. This is caused by modifications to the network of chemical “switches” within our cells. This was news to me and many others of my generation and has proven to be vital knowledge for toxicologists. It is presently one of biology’s hottest topics.

Epigenetics vital to the cell

DNA methylation plays an important role for epigenetic gene regulation in development (Photo: Wikimedia)

DNA methylation in epigenetic gene regulation (Illustration: Wikimedia)

Epigenetics is the study not of changes in the underlying DNA sequence, but the activation or inhibition of genetic switches. Methylation (the addition of methyl groups to the DNA) switches genes off and acetylation (the addition of acetyl groups to the histones, the proteins in which DNA is wrapped) switches them on. Since all cells in a multicellular organism have the same 23 chromosome pairs with their 25-30,000 genes, when you think about it, it is clear that different cells will need different genes to be active depending on their particular functions. Such regulation is really vital.

Now, the new findings showed that these changes can remain through cell divisions for the remainder of the cell’s life and may also last for multiple generations if it occurs in a sperm or egg cell that results in fertilisation. That is to say that the fate of your child can be directly influenced by your diet and, if is is a female foetus, her eggs, that are formed already during the pregnancy, will express the same changes and thus indirectly influence your potential grandchildren. Mind boggling, isn’t it? But of course as usual we have protective mechanisms at work. Reprogramming resets the epigenome of the early embryo so that it can form every type of cell in the body. In order to pass to the next generation, epigenetic tags must avoid being erased during reprogramming. However, in mammals, about 1% of genes escape epigenetic reprogramming and this is sufficient to take epigenetic impact seriously also as an evolutionary tool.

To summarise, epigenetics suggests that the choices you make in your diet and lifestyle can, possibly, lead to changes in how your cells express their genes, with implications for your children and other descendants. It is a reminder that when making choices about what you eat and drink and put into your body, and what you do, you’re not only doing it for yourself, but for future generations and for the future of all of us. And it is actually not necessarily contrary to Darwin’s theory, but rather a complement. New characteristics can be generated and passed on via epigenetics, subject to the same mechanisms of evolution as those with a purely genetic origin.

Epigenetics important for toxicity testing

Toxicologists are spending more and more time on exploring epigenetic changes. Scientists at Washington State University administering dioxin to pregnant rats noticed a variety of reproductive problems and disease in subsequent generations linked to epigenetic changes. The first generation of rats had prostate disease, polycystic ovarian disease and fewer ovarian follicles, the structures that contain eggs. To the surprise of the scientists, the third generation had even more dramatic incidences of ovarian disease and, in males, kidney disease. The same scientists have published studies finding epigenetic diseases promoted by jet fuel and other hydrocarbon mixtures, plastics, pesticides and fungicides, as well as dioxin.

A variety of compounds are considered as epigenetic carcinogens—they result in an increased incidence of tumors, but they do not show mutagen activity. Examples include diethylstilbestrol, arsenite, hexachlorobenzene, and nickel compounds. On the contrary, current research has shown that epigenetic pharmaceuticals could be a potential replacement or support therapy for currently accepted treatment methods such as radiation and chemotherapy, or could enhance the effects of these current treatments.

The field of epigenetics opens new ground in the study of how hazardous substances might cause diseases and reproductive problems. While toxicologists generally focus on animals directly exposed to a compound, it is now clear that this has to be widened to also explore ancestral exposures that are mediated through epigenetic changes in sperm or egg.

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