Courtney Griffins: Epigenetics and The Influence of Our Genes at TEDxOU (Transcript)

Here is the full transcript of gene researcher Courtney Griffins’ TEDx Talk: Epigenetics and The Influence of Our Genes at TEDxOU conference.

Listen to the MP3 Audio: Epigenetics and the influence of our genes by Courtney Griffins at TEDxOU

TRANSCRIPT: 

Nine years ago, I found myself in a doctor’s office, contemplating the nature versus nurture debate from a fresh perspective. You see, I had been trained as a geneticist and had spent my career manipulating DNA and seeing the profound consequences in a lab setting, so I’d always put my money more on the nature, or the genetic side of the debate.

But, as my doctor revealed to me that I was pregnant with identical twins, I realized that my convictions were about to be put to the test. For starters, we had not budgeted on two daycare bills at once. So I kind of half-jokingly started to wonder what would be the consequences maybe, if we just sent one twin to daycare and maybe just kind of tuck the other one in my office drawer during the workday. Despite their identical DNA, I somehow doubted that things would turn out all that well for the twin in the office drawer.

Identical twins have had a profound impact on scientists’ understanding of nature and nurture. Studies on identical twins who were separated at birth and raised in separate households have helped us understand different traits that are more affected by nature, or DNA, versus nurture, or the home environment.

For example, some traits, like IQ or criminal tendencies, are more affected by your DNA than the house that you grew up in. On the other hand, other traits, like depression in men, or your preference for a particular political party, are more influenced by your environment than by your genes.

So what about identical twins who are raised in the same home environment? Their nature and their nurture are almost the same. And yet, any parent of identical twins, myself included, can quickly point out differences in their children. One twin may have more of a preference for certain types of foods, or may have more aptitude for a certain sport or musical instrument.

And sometimes, health differences can arise in these children. For example, there are reports of autism, or asthma, or bipolar disorder arising in one twin at a young age while the other one remains unaffected.

How do we explain these differences, given that the DNA is the same in these children? And for the large part, their home environment has been the same too? Well, it turns out that some of these differences can be explained by a third, very powerful influence on our lives, besides nature and nurture. This is epigenetics.

I’m going to talk to you today about what epigenetics is and how it impacts your life, even if you’re not an identical twin. So before we talk about epigenetics, we need to consider our DNA and how it fits into our cells because, believe it or not, of the 50 trillion or so cells in your body, each one contains about six linear feet of DNA. I mean, if we were to stretch it out, it would be about as tall as a pretty tall man.

So how in the world do we fit that amount of genetic material into something the size of a cell nucleus, which is 400,000 times smaller? Well, the answer is that we do it by wrapping our DNA around clusters of proteins called histones. You can think of histones sort of like molecular spools. And there are about 30 million of these spools in each of your cells. So this helps explain how you fit such a tremendous amount of DNA into a small space. Now we call this combination of histones and DNA, chromatin.

And while chromatin solves this tremendous packaging problem that the cell has, it also presents a new one for the cell. And this is one of DNA accessibility because keep in mind that the functional units of DNA are actually the genes encoded in it. These are the instructions for the cell. These are what tell the cell what to do and who to become and yet, when these genes are tightly compacted into a chromatin structure, the cell is unable to read them, they might as well not even be there. This is where epigenetics comes in.

So ‘Epi’ meaning ‘on top of’ and ‘genetics’, your ‘genes’, literally refers to a set of instructions that sits down on top of our DNA and our histones. Epigenetic marks are small chemical tags which sit down on our chromatin and can help instruct it whether to compact or decompact. And those instructions can then affect how the cell reads the underlying genes encoded in the DNA.

So, to show this schematically, some Epigenetic marks, shown here in red, can help condense chromatin. And when they do this, they obscure the underlying genes, preventing the cell from being able to read them. They turn those genes off.

Other Epigenetic marks, shown here in green, can help decondense the chromatin. And when they do this, the gene becomes accessible to the cell, the cell is able to read it and turn it on. Now these types of epigenetic marks are profoundly influential to our biology.

Consider, for example, what is it that makes our cells different from one another? What makes them look and behave differently? What is it that makes a muscle cell, for instance, look different from a neuron? After all, these cells contain exactly the same DNA but it’s their epigenetic instructions that help tell them which genes to turn on and which ones to turn off. And with those different genes at play, these can become very different cells.

So you might be wondering when does all this epigenetic information get laid down on our chromatin? And the answer is that much of it happens during our embryonic development. So interestingly, when you were first conceived, and you were just comprised of a few, undifferentiated embryonic stem cells, which had the potential to become any cell in your body, your chromatin didn’t have many epigenetic marks on it. It was only as your cells began to divide and received signals and information from surrounding cells, that the epigenetic marks began to accumulate and then the genes began to get turned off and turned on, and the muscle cell became very different from the neuron.

This brings me to a really important point about epigenetics. And that is that, epigenetic marks can be influenced by the environment. And when I say environment, I don’t just mean those surrounding cells that tell a neuron to become a neuron. I also mean, the environment outside of the developing embryo. So the food that the mom eats, or the pre-natal vitamins that she takes, or the cigarettes that she smokes, or the stresses that she encounters at home or at work, can all be transmitted as chemical signals through her bloodstream to her developing fetus, where they can get laid down as epigenetic marks that affect the fetus’ own genes and long-term health.

Now this has been shown experimentally in mice. Mice contain a gene called agouti, which makes them obese and yellow and susceptible to diseases, like cancer and diabetes. This gene and these traits can be passed down from generation to generation through DNA so that an agouti mother will give rise to a fat, yellow, disease-susceptible offspring, if that offspring contains the agouti gene.

Now here’s something interesting about the agouti gene. It can be turned off, if silencing epigenetic marks accumulate around it. So, if a pregnant agouti mother is fed a diet which is supplemented with these silencing epigenetic marks, those marks will be chemically transmitted to the DNA of her embryo, where they’ll accumulate around that agouti gene and effectively turn it off. Her embryo will maintain those marks. So it will be born and grow up to be an adult mouse that’s thin, and brown, and healthy.

Even though this mother is genetically identical at the DNA level to both sets of this offspring, you can see that the diet that she consumed during her pregnancy can affect the health and appearance of her offspring. This has, of course, implications beyond the mouse world, because studies in humans have shown that women who don’t eat well during their pregnancy, who eat bad foods, will go on to have children who are more susceptible to developing obesity and cardiovascular disease.