Friday, December 30, 2011

Epigenetics - We Are More Than Just DNA

Most of us are familiar with the idea that DNA is the template for our body and that our DNA is made up of many genes (sections of DNA that code for specific traits). We understand that our DNA (and therefore our genes) contains the genetic code that created all of our features - our eye color, hair color, ear shape, or any of the other myriad traits that differentiate us from each other. We also understand that our DNA is passed down from our parents, and part of our DNA then gets passed on to our children. One thing we all felt sure about was that our genes could not change during our lifetime and that the only genetic changes that ever took place only happened during conception (or in cancers). As genetic research has advanced, we now understand that this was a simplistic and incorrect view of the way our genes function. The real story is more complicated and yet turns out to also be a lot more interesting.

As often happens in science, our initially simplistic ideas must be updated to incorporate new research and knowledge. A fascinating new area in genetics research (called epigenetics) is now overturning most of our previous assumptions. While we once thought that environmental factors like diet, exposure to toxins, or even our emotional reaction could not change our genes - we now know that they can. Our genes (or at least our “epigenes”) can be changed and how we lead our lives is what determines these changes. Amazingly, some of these epigenetic changes can even be passed down to our children! We can no longer just blame our diseases on our genes. How we live our life may well determine whether our genes hurt us or help us in the long run.

So let’s look at what this new field of epigenetics means for you and your family and how you can use it to your advantage.

Epigenetics, simply put, is the idea that our basic DNA is not the only thing that creates who we are. The coding of the basic DNA molecule, which is made up of four coding bases (adenine, cytosine, guanine, and thymine), is the backbone of the genetic code. We now know that we can alter the expression of this underlying DNA structure through epigenetics.


These two mice are cloned from
identical DNA, but epigenetic
expression makes the left one's
tail grow differently.
Environmental factors can play a huge role in the way our body develops and adapts in relation to our environment. These adaptations are created through epigenetic changes to our DNA. A good example of this is seen with identical twins (who have identical DNA code). While each twin has the identical basic DNA, they nonetheless may express their basic DNA differently. We see this as slight differences in appearance or even susceptibility to disease. Until recently, we didn’t have answers to why this happens. We now understand that this difference occurs through epigenetic changes.

Before we discuss epigenetic changes in more detail, it is helpful to discuss DNA and its structure.

DNA IS TINY AND IMPORTANT

DNA is rather remarkable. A copy of your DNA resides in almost every single cell in your body. It is extremely information dense; just one human chromosome can contain over 220 million base pairs (the building blocks of genes and DNA itself), and we have 23 pairs of chromosomes. A full strand of human DNA, if stretched out end to end, would be about 6 feet long (though extremely thin).

DNA fits into cells by coiling up around protein molecules called “histones”, much like a sewing thread on a spool. Fully compacted in this way, DNA is about 40,000 times shorter. It’s easier to see how this process works than to read about it. (If a picture is worth a thousand words, a YouTube video is probably worth more.)



So, basically, DNA is wrapped around histones and coiled up into little bundles, collectively called chromatin. Well, histones have a tiny chemical “tail” on them that accepts and interacts with certain types of chemicals. These chemical “keys” cause certain histones to react and either uncoil the DNA (in order to express a section of genetic code) or tightly coil up (preventing gene expression), thus altering the shape of the chromatin. There are a few different names of the process, depending on the chemicals that interact with the histone tails, like methylation, phosphorylation, and acetylation, to name a few. Each chemical has different effects depending on the type of histone to which they attach, but this is really more of a technicality and not essential to understand the broader topic.



The important idea is that the basic coding of your DNA is static (it doesn’t change), but the expression of genes can be turned on or off at a given time by these changes to your chromatin. This allows your body to adapt to a changing environment in unique ways. When famines occur, for instance, some genes “turn on” (are activated by epigenetic processes) which make surviving on less food easier.

CHROMATIN REMODELLING

The overall shape of chromatin (DNA and histone structure) is what determines the genes that are active or inactive at any given time. Tightly bound chromatin generally prevents genes there from being active (they are all squished up and can’t be decoded easily). On the other hand, loosely bound chromatin (like an open book) allows genes to be coded more easily thus allowing them to become active. Since the chemicals that attach to histone tails cause the shape of the chromatin to change, they have a direct effect on how our genes are expressed. This process is called “chromatin remodeling” and is the basis for epigenetic changes that occur throughout our lives.

Interestingly, this process is actually how our cells differentiate at the time of conception. We all start out as a single cell which divides into copies of itself, each containing the same DNA. At a certain point, individual cells begin to undergo chromatin remodeling, causing the different cells of the body to express different traits from other cells. That is how we can get liver cells, brain cells, bone cells, or the myriad other specialized cells in our body. While each individual cell has the exact same DNA genetic backbone, the physical shape of the chromatin (DNA and histone structure together) determines which parts of the DNA are active in any given cell and therefore what type of cell it becomes.

EPIGENETICS IS ADAPTATION

A very famous study, done on survivors of the Dutch famine of 1944, showed that the children of pregnant women exposed to famine were more susceptible to diabetes, obesity, cardiovascular disease, and other health problems. Moreover, the children of the women who were pregnant during the famine were smaller, as expected. But surprisingly, when these children grew up and had children, they were also smaller than average. If the famine had continued, this epigenetic effect could have been a survival adaptation.

Without this mechanism to activate and silence genes, we would be much less adaptable. Some scientists now believe that epigenetic changes may help to explain sudden bursts of evolution in human (and other animal) history that previously did not make sense.

EARLY LIFE MATTERS

The idea that what happens to us and what we are surrounded by in our early life (infancy, adolescence, etc.) is one that psychology embraces readily. Recent research into epigenetics suggests that our experiences early in life can also shape our gene expression, making changes that can persist throughout our entire lives. Studies done with rodents suggest that during both early development (and even in adult life), environmental signals can activate chemical pathways that directly remodel their “epigenome,” leading to changes in gene expression and neural (brain) function. Even the licking, grooming, and nursing methods that mother rats use with their pups can cause epigenetic changes to parts of the brain, affecting the long-term behavior of their offspring. These types of effects could potentially explain how some psychiatric disorders develop in humans.

STRESS

Stress appears to be one of the strongest drivers of epigenetic change in people. From an evolutionary standpoint, this makes a lot of sense. When the environment becomes less hospitable to us (causing stress), that is when we most need to adapt to changing conditions. Lack of food, extreme heat or cold, illness, medications, or exposure to toxins are only some of the factors that activate epigenetic changes. They all appear to have one thing in common, they cause some kind of stress on the body, which then tries to adapt.

LIFE CHOICES MATTER

What all of this means is that the choices you make and how you live your life can make changes to gene expression that can last for multiple generations. Even being exposed to toxins in your environment can alter your gene expression.

Many pesticides are especially strong precursors to epigenetic changes (primarily through methylation). Pregnant rats, even briefly exposed one time to the insecticide methoxychlor and the fungicide vinclozolin, showed effects such as decreased sperm production and increased male infertility in their male offspring. The researchers discovered altered DNA methylation of two genes. As they continued the experiment, they discovered the adverse effects lasted in about 90% of the males in four subsequent generations they followed, even with no additional pesticide exposures.

RESEARCH IS ONGOING

We are only beginning to scratch the surface of understanding what environmental triggers lead to epigenetic changes. Furthermore, we do not fully understand the extent to which these changes can last through generations. What is clear is that there is more to what makes us who and what we are than DNA alone. Epigenetic expression and suppression of genes can have a lasting impact not only on our lives, but those of our children, grandchildren, and beyond.

Of course, these changes are not necessarily negative. The healthy choices we make by living a healthy lifestyle with proper diet, avoidance of toxins, and regular exercise can have a very positive effects on our overall health and on the expression of our genes through epigenetics. Every choice and change we make toward a healthier life potentially matters; they aren’t just affecting our life, they may affect our children also.

The study of Epigenetics has become such an important new area of scientific research that each year thousands of studies are now being performed to try to understand this fascinating new area of genetics. In 2008, the National Institutes of Health announced that $190 million had been earmarked for epigenetics research over the next five years. In announcing the funding, government officials noted that epigenetics has the potential to explain the mechanisms of aging, human development, and even the origins of cancer, heart disease, mental illness, as well as several other disorders.

What is becoming more clear is that our lifestyle choices are more far reaching than we could have ever imagined even just 10 years ago. I know that I now take my new years resolutions a lot more seriously. After all, it could be a difference that lasts many “lifetimes”.

I wish you all a healthy and blessed new year. May 2012 bring you and your family health, happiness, and great success in all your endeavors.

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RESOURCES

http://www.youtube.com/watch?v=s7dDd1bvNfA -- The Epigenome At A Glance

http://www.youtube.com/watch?v=eYrQ0EhVCYA -- Chromatin, Histones, and Cathepsin

http://www.youtube.com/watch?v=9kQpYdCnU14 -- How DNA is Packaged


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Researched and written by Dr. Rebecca Malamed, M.D. with assistance from Mr. Malcolm Potter.

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