Epigenetics

HANK GREEN: So say you have a clone, or a secret identical twin. Because, you know, that a twin or a clone is a genetically identical person to you. Which is crazy, but it's true. Anyway, so you have this clone, or your twin, or what have you, and your parents decide that it's too much trouble to keep both of you. And so they give your clone to a kind of sketchy travelling circus. Now, I know your parents probably wouldn't actually do this, but just roll with me for a minute. So for the purposes of this example, let's just say that you grew up living a normal suburban American life, while your clone grew up with less stability and less access to nutritious food and less education. But more exercise, and more access to sword-swallowers and bearded ladies. And let's say you guys are 50 years old or whatever and you get together and have some lunch. So you're sitting there, across the table from your clone. What do you think you see? Well, for starters, Clone probably has a tattoo on its face. And if Clone had stayed in the circus, Clone probably, you know, professionally rides a unicycle over a tightrope, so Clone is probably in pretty good shape. But then again, Clone probably smokes cigarettes, and probably was malnourished as a child, so might be slightly shorter than you. By the same token, let's say that you've been eating Sonic Tater Tots five days a week since 1992, so you're looking a little bit tubby. Plus, you've spent the last 20 years at a really stressful job that puts you at risk of all kinds of weird health complications.

So, at 50, you and Clone would probably look pretty different from one another. But it turns out you don't just look different. You actually have become different. Now, if some scientists looked at your genetic code, they would say that your DNA was still exactly the same as that other person. That is to say, if your genome is a paragraph, all of the letters would be in the exact same order. But on another level, there would be a huge difference. And if we extend this metaphor, we can say that the letters are in the same order, but the spaces and the punctuation are all in different places. Of course completely potentially changing the message of that paragraph.

The study of this genetic punctuation that I'm talking about is called epigenetics, which literally means "above genetics". The epigenome doesn't change your DNA, but it decides how much or whether some genes are expressed in different cells in your body. Epigenetics looks at what happens to your genes over the course of your life, and whether those changes could be passed down to your children or even your grandchildren.

So here's the way epigenetics works. You have billions of cells in your body, and they each contain your DNA. The same exact blueprint of your genetic code. But just because they have the DNA doesn't mean they know what to do with it. They need outside instructions from these little carbon and hydrogen compounds called methyl groups. The way these methyl groups control the genome is by binding to a gene and saying, "do not express this gene". Methyl groups bind differently to your genome and a skin cell versus, say, a tongue cell or an eyeball cell. And that is one of the ways a cell knows that, "hey, I'm a skin cell", or "hey, I'm an eyeball cell", or "hey, I'm a muscle cell".

In addition to methyl groups, epigenetics is also controlled by histones, which are proteins that are basically the spools that DNA winds itself around. Histones can change how tightly or loosely the DNA is wound around them. If they're more loosely wound, the genes can express more, and if they're more tightly wound, they express less. So whereas the methyl groups are more like a switch, the histones are more like a knob.

Every cell in your body has a distinct methylation and histone pattern. And that is what gives every cell its marching orders.

Think of your genome—the DNA—as the actual hardware of the computer, while the epigenome is more like the software which tells the hardware what to do.

The genome is what's going to be doing all the work. But the epigenome is going to be telling it what to do. So the hardware of your DNA is going to be the same throughout your entire life. But these epigenetic tags do change throughout your life. And they decide what genes get expressed or not.

Now, epigenetic information in a cell isn't permanent. It can change throughout your life, and it can be hereditary. And it can change over time, especially when your body is going through a lot of changes, like, say, during puberty. A bunch of methyl groups kick in there like, "okay, you guys over here, you're gonna have to start growing hair, and you guys over here, I really need you guys to get behind, giving this guy some really horrible acne". Or, like, when you get pregnant, which, hopefully, I won't, but when you do, your epigenome has to be like, "alright guys, everything's about to get a whole lot bigger in here, and we're going to have to pass something the size of like a Merriam-Webster's Dictionary through that little pipe over there, so let's get this thing done!"

But it's not just these dramatic times when the epigenome is changing. It changes subtly throughout our entire lives. And it changes based on a lot of environmental factors. Like what we do, what we eat, what we smoke, and how stressed out we are on a daily basis. Scientists have found that things like a bad diet can actually lead to methyl groups binding to the wrong place and making mistakes. And with those bad instructions, cells become abnormal, and become a disease. And then basically all hell breaks loose, and you get cancer or something.

Epigenetics is a very young science, though we've known about the epigenome since the 1970s. It's only been for the last 20 years we've known what effect these epigenetic tags are having on our DNA. And even after they got all of that business straight, scientists still thought that all of our epigenetics tags were stripped off of our genome before they were passed on to our children. So if you started smoking ten packs a day when you were ten years old, that would certainly be a horrible health decision for you, but you wouldn't necessarily be harming your unborn children in any measurable way. However, the thinking on that is changing pretty rapidly. Because it's true that a lot, even most, of the epigenetic information from a parent is stripped off of the embryo's genome in the first few days, and fresh ones are created specifically for this new person, however some of these tags get stuck on the genome and are passed down from generation to generation. And it just so happened that the more they study this, the more it looks like bad epigenetic information is being passed from generation to generation. And this is a whole new way to think about how we pass information between generations. Your grandmother was making dietary decisions that affect you today.

As we experience all these new strange epidemics: diabetes, autoimmune disorders, cancers, that weren't appearing in previous generations, it's starting to look like these may be caused by epigenetic information passed down from our parents. I know, it's such an unbelievable buzzkill, there's no point in our lives when we can do anything without guilt anymore!

The discovery that the environmental factors of parent experiences can be passed down from generation to generation was sparked in the 1980s. And this happened when some scientists were looking at the birth and death records of some people who lived in 19th century Sweden. It's a weird place to find a genetic revolution, but there it is. It wasn't just any place in Sweden. It was in Norrbotten, which is the northern most county in Sweden, which is literally in the Arctic Circle. And despite the fact that Norrbotten was literally the worst place you could possibly choose to live in Sweden, there were some people living there in the 1800s. And they were completely cut off from the rest of the world. Let me clarify. These people were isolated. Like, if they didn't have a good crop year, people died. No, it wasn't ideal, but you know, they didn't ask me my opinion so I'm not giving it. So anyway, these people subsisted entirely on what they grew and the animals that they raised. And like I said, sometimes they starved. But sometimes they had huge bountiful years of plenty. And when that happened, people totally went ape crackers. I mean, of course they did, because they were so freaking hungry, and then all of a sudden there was all this damn food everywhere. Anyway, there was a public health specialist who was looking at the effects of the people who grew up in the really bad starving periods of time versus the people who grew up in the eat-all-you-can-at-the-smorgasbord years. And you might already be guessing what they found out.

People who went from relatively slim pickings to feed your face until you have to barf and then do it all over again in a single season, those people died and average of six years sooner than their starved-out counterparts. And you know what sucks? So did their kids. And so did their kids' kids. Boo epigenetics! So of course, now we all know, and we're all going to stop doing unhealthy things, starting today. Unless the damage is already done. The damage is almost certainly already done. But hey, epigenetics brings good tidings along with bad ones. For instance, we now know that certain types of cancer are caused by misplaced epigenetic tags. And scientists are now developing drugs that can silence the bad genes that were supposed to be turned off in the first place. Additionally, until recently, we thought that genes were the end all and be all of who you got to be. They were your blueprint, and you couldn't escape them. This outlook is not just kind of pressing, it also leads to a yucky sort of social prejudice. Because when you look at data without considering social and epigenetic factors, it might look like people with less money are less intelligent. So just, like, fifteen years ago, there were scientists saying things—in public, mind you—like "some people just have good genes for intelligence and it just so happens that the poor people don't. Oh, it's so sad, too bad poor people, but you have bad genes". Well, turns out that that is not even a little bit true. Not only are there a huge variety of social factors that affect how well people do on intelligence tests, but a genetic trait is also not just a product of genes. It's also a product of environment. Any one person's genome is determined by any number of decisions made by any number of their ancestors. And right now, you are making decisions that are going to affect people who are alive long after you are dead. No pressure or anything. And so I'm glad you could watch this. Because when you and your clone are in your 60s and you sit down and have lunch and he brings his son and his son has a tattoo on his face, he did not inherit that from you.

This is Hank Green for the SciShow. We hope you learned something.