Epigenetics: the ever-changing genetic landscape within us
by Dyani LewisWhen it comes to your health, the genes you inherit from your parents and grandparents play a significant role. But it’s not just about their genes; you can also be affected by the environmental factors they encountered.
Have you ever wondered why identical twins aren’t actually identical? They have different personalities, of course, but they also go on to develop different diseases and often die of unrelated conditions – one may die from heart disease, while the other succumbs to cancer.”People have focused over the years on similarities between twins,” says epigenetics researcher Associate Professor Jeff Craig, from the Murdoch Children’s Research Institute. “But there are a lot of differences in behaviour and diseases, so something else must be going on.”This seems odd, if you consider that each twin in an identical pair contains exactly the same set of genes inherited from their parents – they are clones. Many of the differences between the two are due to what scientist call ‘epigenetics’ – genetic changes that affect the way in which your genes can be turned on or off in different tissues and at different times throughout your life.Epigenetic changes can be the result of your diet, lifestyle and environmental toxins you may be exposed to. But they can also be programmed before birth due to the diet and experiences of your mother, father or even grandparents.
How do epigenetic changes alter genes?
Many of us are familiar with gene mutations – changes to the sequence of chemical letters in DNA that make up a gene. Mutations occur throughout our lives due to errors made when a cell copies its DNA during cell division, or due to chemicals and radiation. Mutations present in sperm and egg cells can cause genetic disorders such as cystic fibrosis if inherited from our parents. Environmental factors such as UV light can also cause mutations in our cells that can go on to cause cancer.In epigenetic changes, the sequence of chemical letters that make up our genes don’t change. Instead, modifications to the DNA or to the proteins that help to pack the long strands of DNA into our cells are added or removed. These modifications can determine whether or not a gene is active in a particular cell.During development, precisely choreographed epigenetic changes are an important way for cells to shut down genetic programs that are no longer required. For example, a developing blood cell can become either a red blood cell or a variety of white blood cells. Once it has committed to the red blood cell pathway, it no longer needs genes for becoming a white blood cell, so these genes are silenced.Although many epigenetic changes are a part of healthy development, several have been linked to disease.
Epigenetic programming starts before birth
In the earliest stages of embryo development, when we are little more than a ball of cells, epigenetic changes are already taking place throughout our genome.Some of these changes lead to conditions that show up in childhood. For example, a recent study found that fragile X syndrome, a common form of intellectual impairment, is caused by epigenetic silencing of a gene required for normal brain development.Other epigenetic changes only become evident later in life. When World War II ended, the Dutch population was plunged into a period of famine. Research has shown that children conceived during this time were more likely to develop heart disease in later life than children conceived in more plentiful times. Furthermore babies whose mothers only experienced famine towards the end of their pregnancy weren’t affected.Evidence from animal studies adds further support to a role of epigenetics in what is now known as the ‘developmental origins of health and disease’. Rats born to under-nourished mothers have an increased chance of developing type 2 diabetes.Common nutrients, such as folate, vitamin B6, vitamin B12 and methionine alter epigenetic markers in DNA. Sheep deprived of these nutrients during early development in the womb were fatter and had higher blood pressure as a result.Certain toxins can also affect later health if ingested during pregnancy. In mice fed food containing bisphenol A – a compound commonly found in plastic food containers – pups were more likely to develop obesity and type 2 diabetes.A mother’s diet is not the only thing that can influence epigenetics in the womb.“There are also factors beyond our control,” says Craig. The location in the uterus where the embryo implants, as well as the size and efficiency of the placenta and umbilical cord – which Craig refers to as “supply line” factors – can alter the epigenetics of an unborn baby.“We have a tendency to point the finger at the mothers when in reality it’s a whole set of factors.”
Fathers also influence our epigenetics
A striking example of the impact of a father’s diet on his children comes from the remote Overkalix region of Sweden. Medical records spanning generations were analysed and it was discovered that boys who ate poorly in the years just before puberty – around age 9-12 – had sons with lower rates of heart disease. In contrast, boys who gorged themselves during good harvests in pre-pubertal years had grandsons more likely to develop diabetes.These effects are likely explained by epigenetic changes that occur in the cells that go on to develop into sperm. But the mechanism that is responsible for carrying the effects of diet across multiple generations is yet to be identified.A recent study in mice found that obese males fathered male offspring with reduced fertility. Importantly, a diet and exercise intervention to curtail the obesity in the fathers was able to reverse this effect.
But our epigenetic fates are not sealed in the womb or even in early childhood. Just as healthy diet and lifestyle can counteract many genetic predispositions that we may have, sensible choices can also counteract early epigenetic programming.
The epigenetic changes that occur throughout our lives often take place in just a subset of cells. Exercise has been shown to change the epigenetic markers in both fat and muscle cells, which may explain some of the health-promoting effects of physical activity.Sunlight, asbestos, tobacco smoke, alcohol and hair-dye have also been shown to cause epigenetic changes in certain tissues of our body. Whether epigenetic changes are involved in the early stages of cancer is still under investigation, although many cancers are known to have widespread alterations to epigenetic markers compared to healthy tissue. Drugs that alter epigenetic markers are already in use to treat some cancers.Epigenetic drug therapies are still very new, though, and we are a long way from using them to tinker with the markers that were laid down in the womb or programmed during our father’s childhood.