EPIGENETICS – The end that was really just the beginning

On April the 14th, 2003 the Human Genome Project was finally presented to the world. It was the map of all 25 000 genes that gave the paperwork of how to make a human body. It was the 3 billion base pairs that had been sorted into a readable order of 3-letter words, or codons. It was a miraculously unique collaboration of international goodwill, where scientists from the USA, UK, France, Germany, Japan and China all shared freely their research on this most important topic. It started officially in 1990 when James Crick was appointed director of operations, but it had really started 43 years previously when the same ‘honest Jim’ Crick, along with his partner Watson, had received their Nobel prize for discovering the double helical structure of DNA. They had discovered that the same DNA that had been described by Gregor Mendal in the 1850s whilst tinkering with sweet peas, was in fact made up of just 4 base pairs, A, G, C, and T. These 3 billion base pair letters are the core of everything human. These letters are connected into the 3 letter codons. These codons combine to form the 25 000 genes that tell the body to make all the proteins that are the enzymes, the workers, the building blocks that make us who we are.

April 14th 2003 was a glorious day, a day of back-slapping celebration. The work of nearly 150 years was done. But the truth was, it had only just begun.

The question had arisen many years before: if the script of our genome is the same in every cell, then why doesn’t every cell make the same stuff all the time? If there is the same DNA in the cells of teeth as there are in the cells of the ear, then why don’t we have teeth hanging out of our ears? Why do toe-nails only grow on toes? Why do we only get scar tissue on a wound, why doesn’t it grow all over the skin? The answer had to be because some signaller tells the genes to switch on when it is needed and switch off when it isn’t. Why does bone marrow make only a certain number of white blood cells and then stop? What goes wrong in leukaemia in this messaging pathway to the DNA that causes the marrow to continue making endless white blood cells? What triggers this faulty messaging that results in the cancer that we fear and know so well?

To understand this we need to go all the way back to the 1950s description by Watson and Crick of the DNA double helix. Every cell has 23 chromosomal pairs and each one of these pairs of chromosomes is made of a beautifully intricate spiral of information. The structure of a chromosome is so small that we cant see it, but in microscopic terms it is as large and complicated as the Starship Enterprise. It is made up of supercoils of DNA and each supercoil is made up of numerous smaller coils of DNA. Each coil has been spun around a histone protein ball, which needs to unwind before anything can be read and acted on. Once it has been unwound, the DNA double helix is revealed which shows the supporting sugar strings and there hanging on to the edge of these strings are the famous 4 base pairs A, G, C and T. It is the epigenetic system that allows sections to be read and sections to be ignored. It is the epigenetic system that tells ear cells not to grow into teeth. It is the epigenetic system that tells the skin when to make and when not to make scar tissue.

If the genome is the script, then epigenetics is the music. It is how the script is played, sometimes softer, sometimes louder, sometimes not at all. It is the essence of life and is influenced by what we do, think and eat on a continual basis.  Central to epigenetics is the much-ignored methyl group. If there were an award for the most important factor for life, then oxygen, glucose and water would all clamour for podium places. However the little known methyl group is right up there with them. Methyl groups are the keys that unlock successful detoxification pathways in the liver. Methyl groups are essential for the formation of happy brain hormones and removing excessive anxiety hormones. But more than this, methyl groups are central to the DNA of every cell. They switch on or off the epigenetic expression of the DNA genome. If methyl groups attach to the codons, then they encourage the reading of those codons. If they attach to the histone protein that coils the DNA up tight, then they block the reading of the DNA . In this way, methyl groups become the conductors of the DNA orchestra, directing the DNA to switch on or off at their bidding. Epigenetics could be described as the cloud of methyl groups surrounding every chromosome, prodding the DNA to play louder or softer on a continual basis. Every toxin that we are exposed to can have a negative influence on this process. Every nutrient that we consume can have a beneficial influence on this process. Even the loving touch from another person or the painful smack from a bully can have a positive or negative influence on our epigenomic expression.

This was demonstrated in an experiment on Agouti mice. These mice have an Agouti gene, which if switched on makes the mice yellow and fat and if switched off makes the mice brown and thin. These mice have been used successfully to demonstrate how different toxins can influence this gene and leave the offspring either yellow and obese or brown and thin. In a particular experiment described in 2008, pregnant mother mice were either exposed to BPA (Bisphenol A) – an estrogen sensitising toxin found in plastics, or were protected from the BPA exposure for 2 weeks of their pregnancy. The result was that the offspring from the BPA exposure, were all yellow and fat, whilst the offspring of the healthily fed pregnant mothers were all brown and thin(1). This seminal study shows that just a short exposure to a toxin will influence the epigenome of the developing mouse fetuses.

The Dutch and the Danes have shown in separate studies that societies subjected to starvation in the second world war, had epigenetic influences up to 2 generations later, causing a high prevalence of obesity in the offspring of that society.

Practically speaking, this means that whatever we do on a daily basis will influence our genes. It means that we may have weak genes, but that with appropriate manipulation of our epigenome, we can alter the expression of that weak gene. For example, someone may get a gene report saying their CYP1A2 gene is weak. The CYP1A2 gene codes for a liver pathway that helps to remove caffeine and other toxins from the body. If it is weak it means that one would feel the effects of coffee for many hours after drinking it. If it is strong, then you could have a coffee and go straight to bed without being kept awake. Someone with a weak CYP1A2 gene, who also has high blood pressure, might find that if they drank excessive coffee then the caffeine that was not being removed could worsen their hypertension risk. The advice might be for them to avoid drinking coffee altogether. However the wonders of epigenetics gives a different story. If someone with a weak CYP1A2 gene were to drink just 1 to 2 coffees a day they would find that they would start to up-regulate their gene. They would start to remove caffeine quicker and they should be able to drink 1 to 2 cups of coffee a day without it affecting their blood pressure and without it keeping them awake at night.

Another example is the FTO gene. This is the FaT and Obesity gene and those who carry the weakened gene can really struggle to lose weight if they happen to be obese. However, eating your greens on a daily basis has been shown to donate methyl groups, improve the epigenome and improving weight loss by 30%(2).

I recently saw a very sad comment on a social media site. Someone who had been doing well on their low-carbohydrate high-fat diet, had received gene test results to say that they over-absorbed fats. They had been told to cut out all saturated fats from their diet. This is terrible advice and in no way accurate. Firstly, these gene tests do not entirely preclude anyone from eating saturated fats. Secondly, cutting out sugar from that persons diet would have a profoundly positive influence on the expression of fat cells. There is generally something positive that we can do to help epigenetics counter the bad news of a faulty gene report.

We have come a long way since the Human Genome Project was completed on that heady day in April 2003. The insight we have gained from epigenetics has shown us that our genome is just the beginning. It is just the script and how the music is played is entirely up to our epigentics. This means that the activities that we choose on a daily basis will influence our genes and perhaps those of our children for years to come.

As has so often been quoted, ‘your genes are not your destiny, but they are your tendency.’ The point about doing gene testing is not to depress us about how useless we are compared to the next person. Every weak gene we find gives us an opportunity to support it with healthy methylation to optimise who we are.

1 Dolinoy D. The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr Rev; 2008; 66

2 Kilpeläinen TO, et al.Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. Pubmed: 2011.