How genes are expressed differently without changes to DNA
Written by Assoc Prof Mark Umstad, Obstetrician & Gynaecologist, and AMBA Patron
Classic twin studies compare similarities between monozygotic (identical) and dizygotic (fraternal) twins. For any condition in which monozygotic twins are more similar than dizygotic twins, there is an implication that there is a more significant genetic than environmental influence. Because twins share many aspects of their environment including the uterus, parents, home and schooling, differences can be assessed in relation to how similar their genes are. In recent years, it has been recognised that there is more to this “nature versus nurture” concept. This is where epigenetics has developed.
What is epigenetics?
The technical definition is that “epigenetics is a heritable change in gene expression without changes to the DNA sequence”. What this means in practice is that all of the cells in our bodies have exactly the same DNA within them, but they can be expressed in very different means. For example, one cell may turn into a liver cell, another into a muscle cell and another into a fat cell, despite all of them having identical DNA. The difference in how these cells develop is due to epigenetic influences.
DNA and methylation
To understand epigenetics, it is important to have a basic understanding of DNA. DNA, or deoxyribonucleic acid, is the part of the cell that includes all of the genetic instructions for almost all living creatures. It is made up of a combination of acids and proteins in the famous double helix discovered by scientists Watson and Crick, for which they won the Nobel Prize. Within the strands of DNA are varying combinations of chemicals, which code for all of our genetic information. Recent research has shown that parts of the DNA can be turned on or off by adding or releasing a chemical called a methyl group. It is important to understand the DNA is not changed by this process, but simply sections of it are turned on or off and therefore certain proteins are either made or not made. As a normal human has around 30,000 genes, it is important that there is control over which of these genes are active or inactive. It is the study of what turns these genes on and off that constitutes epigenetics.
Epigenetic changes
For example, many of us have the potential within our DNA to develop five or six different types of cancer. As long as those cancer genes are turned off, we do not develop that type of cancer. However, if these cancer genes are turned on, then a cancer has the potential to develop. Cigarette smoking is a classic trigger for epigenetic changes to DNA. It is often the influence of cigarette smoking that turns the genes for lung cancer on, when in non-smokers these genes may be suppressed. Epigenetics can be changed by many environmental influences. These might include diet, temperature, stress or hormones. In the animal world, we know the queen and worker bees are genetically identical, but the queen bee – which alone is fed on royal jelly – lives 35 times longer and is substantially bigger than the genetically identical worker bee. It is the epigenetic influence of royal jelly that accounts for these differences. Nutrition is one of the major areas that epigenetic researchers study. Historically, the children of mothers who were pregnant at the time of the Dutch famine during the Second World War had different levels of DNA methylation than their brothers and sisters who were born outside the period of famine. The children who were born during that famine have been shown to have a significant increase in chronic diseases in later life. One of the interesting aspects of epigenetics is that the effects maybe trans generational. This means the environmental exposures from one generation can have an effect on the next generation and perhaps the one after that. We know that fathers who smoke before puberty have more obese sons.
We also know that when grandparents’ food supply was restricted, their grandchildren will live longer, but where the food was abundant the grandchildren have shorter lives and a higher risk of developing diabetes.
Twin research
The interest in twins relates to trying to solve the classic “nature versus nurture” argument. To do this, twin studies have tried to determine heritability. This is the estimated contribution of a genetic factor in determining a disease. A disease of high heritability means that a significant proportion of the cause of that condition is genetic. A disease of low heritability reflects more environmental than genetic influences. By studying twins, it is possible to establish an accurate estimate of how much genetic influence there is on the development of a particular condition. Although results between different studies may vary considerably, there are a number of conditions that are generally recognised to be of high heritability. For example, autism, epilepsy and schizophrenia are all of high heritability. This means there is a very good chance that if one monozygotic twin has the condition, then the other will also develop it – but this is by no means a certainty.
Some conditions are of of low heritability, meaning the environment plays a much more significant role than genetics in the development of the condition. Various forms of arthritis and autoimmune conditions generally fall into this category. Much of the research in twin studies and epigenetics has been focused on so called “metabolic conditions”. These generally include high blood pressure, diabetes and heart disease. The role of diet and nutrition as triggers for epigenetic change is being very closely studied. We now know that epigenetic changes that can be identified, even at the moment ofbirth, can help predict the likelihood of these metabolic conditions later in life. This has led to the idea that “you are what your mother ate!” Given that epigenetic changes may be transgenerational, “you may also be what your grandmother ate!”
The exciting aspect to this research is that there is potential for interventions to be introduced in pregnancy to reduce the risk of complex diseases in later life. That is, modifying diet or nutrition during pregnancy, or controlling gestational diabetes more carefully, may reduce the risk of children or grandchildren developing cancer, high blood pressure or diabetes later in life. This is a relatively new aspect of research in medical science, but is extremely exciting. As parents of twins, you may well be approached by twin researchers to be involved in epigenetic studies.
Hopefully this article gives some background as to why this research may be of great importance in years to come.
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