It's Epigenetics, Honey!

Why identical twins are not so identical after all..
24 June 2015

SINGLE-HONEYBEE

A honeybee

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Identical twins don't look exactly identical, but if they share every single gene, how can this be?

Some changes are down to the environment, but others are down to something called epigenetics. The Weasley twins in the Harry Potter film adaptions are played by James and Oliver Phelps, a pair of identical twins. These two brothers look almost the same, but have a few little differences like the shape of their eyes, the line of their top lip, and one of the twins is a little taller than the other. As with almost all sets of identical twins, they have little differences due to epigenetic changes which they have accumulated independently from one another. These changes have altered their genomes in different ways and lead to these minor differences.

What is Epigenetics?

Most of us know that we all have a genome which contains a set of instructions for how we are all made. This genome contains DNA, a code which can be translated to make proteins which are used to make things like our hair, skin and the various parts of the cells in our bodies. The genome is made of a set of building blocks called bases. There are four different types of bases called A, T, C and G. They bind to one another and form the familiar double helix shape which we all recognise.

This set of instructions is however, not rigid. Our body uses it like we use a cookery book; if you're baking a cake you often scribble in the margins of the recipe book and cross out ingredients or sections to change how you want your cake to look or taste. You might add extra chocolate chips if you have a bit of a sweet tooth or leave out some ingredient which you don't like, such as raisins. However, the words originally printed on the page remain the same. These little changes are similar to what we call epigenetic changes in the genome. These are alterations to our genetics which do not change the actual genetic ATGC code.

Epigenetics can be imagined as a type of molecular switch which has the ability to turn on or turn off some of our genes. This switch can turn on or off during our lifetime and does not have to stay in the same position for our whole life. This allows outside factors such as diet to impact on our genes. These epigenetic alterations can be passed down from one generation to another. Armed with an understanding of what epigenetics does, let's investigate how we accumulate these changes.

How does it work?

There are a variety of complicated molecular mechanisms by which these epigenetic changes can happen. Some have to do with the way that our genome folds itself to fit into our cells while others involve adding or removing chemical groups to the genetic sequence much like Lego pieces.

One of the best studied mechanisms is called DNA methylation where a methyl group (carbon and three hydrogens) is added one of the DNA bases, and sticks out of the side of the DNA helix. This addition to the usual DNA shape prevents the DNA being translated into protein, effectively turning off the gene so it no longer works. This tiny change can have a big impact, so where do we see it in practice?

Queen Bee

Epigenetics isn't something that is a solely human phenomenon and there is an abundance of examples of epigenetic effects in action in the plant and animal kingdoms. One of my favourites of these examples came to light when a team of international sciences sequenced the genome of the honeybee.

These amazing animals work in hives with thousands of and have a complicated social hierarchy structure. Every bee has a job, be it a worker or a drone. However, there is only one queen bee per hive. This queen bee produces all of the offspring and directs the activity of the other bees by producing certain chemicals. The queen bee is fed a unique diet which gives rise to her royal status. When young bee larvae are born, they are all initially fed with a nutritious substance called royal jelly. The worker bees are soon weaned onto a mixture of nectar and pollen while the chosen queen bee is fed royal jelly well into adulthood and in much larger quantities than the other bees. There are massive differences between the queen and the other bees because of this difference in diet and upbringing. The queen bee is larger, lives longer and is fertile, unlike the rest of the female bees.

The environmental differences between these different types of bees results in different levels of expression of certain genes in the bee's genome. These changes in gene expression result in massive changes in the behaviour and appearance of the bees. This is epigenetics in action! However, the Honey Bee isn't the only species which can undergo epigenetic changes; amazingly we too can adapt our genetics in response to the environment.

Famine children

In the Netherlands near the end of the Second World War, there was a severe famine which is known as the Dutch Hunger Winter. During that time, the Netherlands had a serious shortage of food and fuel due to a blockade by the Germans. The beautiful Belgian born Hollywood actress; Audrey Hepburn was in the Netherlands at the time of this famine, which ended when she was about 16. People were desperate for food, with rations reduced to roughly 1000 calories per adult, and many resorted to eating tulip bulbs and grass in an attempt to stay alive. Millions were affected and tens of thousands died of hunger.

This event was relatively unique in that the food shortage emergency occurred in a modern, well developed country whose citizens were usually well fed and lived in good conditions. These people had only one period of severe famine, at one specific point in time. This has allowed scientists to follow up the effects of this Hunger Winter, in a specific, well defined population and the generations which followed. It has allowed us to learn a lot about how famine affects human health and our genetics.

The effects of this Hunger Winter lived on in the genomes of the people like Audrey who had been alive to suffer through it, but some of the most startling effects were seen in children who had been in utero during the time. Scientists found that children's birthweights were affected by when during the pregnancy the mothers were malnourished. Those who were starving for roughly the first three months of their pregnancy had children with normal birth weights, but those who were starving towards the end of the pregnancy had babies with very low birth weights. This made sense, because the babies who were well nourished towards the end of the pregnancies had time to 'catch up' on their weight. However, what was even more interesting was that the babies with low birth weights remained small throughout their lives while those with larger birth rates from this time were very prone to obesity. However, science is an ever changing field and often fraught with controversy. There have also been studies published which claim that this difference in birth weight may have been caused by other factors including social status of the mothers. There have also been links drawn to these birth rates and other long term health problems including schizophrenia and type-2 diabetes. These lasting effects are due to epigenetic changes which occurred during the baby's time in utero because of the nutritional deficiencies during the Dutch Hunger Winter.

As we can see from the honey bee and the effects of the Dutch Hunger Winter, it's interesting that even though we are born with a set of genes; a set of instructions for us, we can change how we use those instructions through our diet, behaviour and environment. The nature/nurture debate has been raging for many years now as we try to decide if humans are a product of our genetic code or how we are raised. Perhaps epigenetics suggests that a combination of both is what makes us who we are.

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