Epigenetics

Theme: Health issues and Disease

Venaya Binwani

Have you ever wondered why identical twins never turn out to be identical? Monozygotic twins are born with the same genetic code (if we ignore any random mutations), so why can they grow up to be so different? Of course, this would have to do with environmental factors, such as lifestyle, diet, stress and exposure to chemicals. However, in recent years, scientists have begun to explore how these environmental factors may interact with our genes to shape the way in which they are expressed. For a long time, we believed that our genetic code was simply made up of the 23 pairs of chromosomes we inherit from our parents - but the reality is that there are a vast number of complex molecules that interact with our DNA that shape how our body processes the information stored within our genome. This is known as epigenetics - the science of external changes to our genes without modification of the nucleotide sequences themselves. [1][2]

To clarify, our genome refers to all the genetic information we store in our bodies. Each cell in our body, regardless of whether it is a white blood cell or a nerve cell, all contain the same genetic information. So why do our white blood cells produce antibodies whilst our nerve cells synthesise neurotransmitters? This is because when our cells specialise from stem cells, certain genes get switched on and others get switched off. This does not mean that these cells have a different set of chromosomes or lose part of the genome when they differentiate, but it means that only the relevant parts are processed and read depending on the role they are meant to play. You can think about it like a huge instruction booklet that dictates how the human body operates. Each type of cell in our body will read a different chapter in the booklet, depending on which process or mechanism they are concerned with. If you are an eye cell, you are simply not going to read the instructions on how to produce hydrochloric acid as your stomach cells would - because that just wouldn’t be pretty. [1][2]

So, how does epigenetics tie into this? Well, our DNA does not simply float around the nucleus on its own. It is surrounded by chemical tags, proteins, and other molecules that play a role in the processes of transcription and translation. These two processes are responsible for turning the ‘instructions’ in DNA into proteins, which essentially sustain the millions of biochemical processes that take place in our bodies. So when changes to these biochemical tags occur, it is going to influence how genes are read and expressed, and can influence how much of a particular protein is produced - or whether it can be produced at all. An example of this is a methyl tag, which attaches to certain regions of DNA to inhibit transcription. It is then our environmental factors such as diet, medication and exposure to chemicals that can influence where and how many of these methyl tags attach. To keep consistent with our instruction manual analogy, we can look at these chemical tags like little scribbled or highlighted sections on the text, that hinder or enhance the extent to which instructions are carried out.

In one study conducted on rats, baby rats (pups) were isolated from their mothers for a period of time. Due to the lack of attention received during their infancy, these rats developed heavier methylation in stress regulation genes, which impaired their stress management mechanisms throughout their lifetime.[2] It would be interesting to consider whether a similar phenomenon would be noted in humans too. 

Another interesting phenomenon was observed in humans, during the 1944-1945 famine in the Netherlands, known as the Dutch Hunger Winter. When the Nazis cut off food supplies from the Netherlands, over 20,000 people died of starvation. During this period, thousands of children were born much smaller than normal, as their mothers were malnourished during pregnancy. It is reported that an individual’s rations consisted of less than 1000 calories per day - which is significantly less than the 1,800 calories recommended for women in their first trimester. Whilst these children probably were not starved throughout the later years of their life, scientists discovered an elevated incidence of schizophrenia, obesity and diabetes in people born during the famine, compared with their siblings who were born either before or after. [3]

Follow up studies have found that this may be to do with the methylation of certain genes such as the IGF2 gene which is involved in the growth and development of cells in an embryo. An epidemiologist at Columbia university reviewed death records of hundreds of thousands of people who were in utero during the famine, discovering that these people had a 10% higher mortality rate above the age of 68. [2]

Interestingly, the changes to the epigenome that occur during pregnancy, are especially malleable during the first 10 weeks after conception. In a study conducted, researchers found that mothers exposed to domestic violence during the early stages of their pregnancy, gave birth to babies with higher levels of methylation on their NR3C1 gene, making them more susceptible to distress. However, no such correlation was found if mothers experienced the same stressor before or after pregnancy.[4] What’s even more interesting, is that these epigenetic changes not only get passed on from mother to fetus, but to the next generation of children too. It is crazy to think that the experiences your mother had whilst you were in the womb could influence how your genes work today, but more surprisingly, the genes that you may pass on 10 years from now. [1]

Perhaps we have more control over our seemingly uncontrollable DNA than we originally thought.

References: 

1. Sci-Show (2012) Epigenetics. Available at: https://www.youtube.com/watch?v=kp1bZEUgqVI date accessed: 9/11/2020

2. TED-Ed (2016) Carlos Guerrero-Bosagna. Available at: https://www.youtube.com/watch?v=_aAhcNjmvhc . date accessed: 9/11/2020

3. Zimmer, C., 2018. The Famine Ended 70 Years Ago, But Dutch Genes Still Bear Scars (Published 2018). [online] Nytimes.com. Available at: <https://www.nytimes.com/2018/01/31/science/dutch-famine-genes.html> [Accessed 10 November 2020]. 

4. Palma-Gudiel, H., Córdova-Palomera, A., Leza, J. and Fañanás, L., 2015. Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review. Neuroscience & Biobehavioral Reviews, 55, pp.520-535.

Glossary:

1. Monozygotic twins: twins formed from the same fertilised egg (zygote), which contain the same genetic material

2. Chromosomes: structures that contain our genetic material

3. Genome: all of the genetic material in one particular organism

4. Nucleotide sequences: Our DNA is made up of 4 types of nucleotides: Adenine, Guanine, Thymine and Cytosine - the combination and order of these chemicals determines the traits we possess

5. Stem cells: undifferentiated cells that have no specified function or role. They develop into a particular type of cell depending on what the body needs. They are produced in the bone marrow.

6. Transcription: the first stage of protein synthesis where our genetic code is read and a copy of the ‘instructions’ is made by enzymes

7. Translation: the copied set of instructions from transcription are used to manufacture proteins in this process.