Epigenetics gives Darwin the Finger
Oh, hey guys, remember in my last post when I said I would tell you more about epigenetics at a later date? Well, turns out that day is today. Are you excited? I’m excited. Before we dive in, let’s take a step back and review what you learned about genetics in high school: remember Gregor Mendel? He bred a bunch of pea plants with different characteristics, like flower color and pod size, then tracked which characteristics were passed on to the next generation. He discovered the concept of dominant and recessive genes that interact when two animals/plants/what-have-you get it on. You probably did those little Punnett squares in middle school to see what color eyes an imaginary baby would have:
Mendel’s theories of genetic inheritance fit in nicely with Darwin’s theory of natural selection. Two animals get it on –>create babies with slightly different characteristics –>turns out one of those characteristics is much better at not getting you killed –>baby with the better characteristic lives long enough to make lots more babies with that characteristic –> gradual genetic change ensues. So when you combine Darwin’s theories with Mendel’s observations, you get genetic inheritance as we’ve understood it since the late 1800’s.
You have to understand just how ass-backwards theories of inheritance and evolution were before Darwin and Mendel. Before natural selection started gaining momentum, one of the most popular theories was that of Jean-Baptiste Lamarck. He suggested that animals modified their own bodies through experience and force of will, and the acquired changes they made were passed on to their offspring. For example, a giraffe has a long neck because this one time a giraffe with a normal sized neck decided the leaves at the top of the trees were way tastier, so it stretched its neck as high as it could to reach higher leaves, and then when it had a baby, that baby had a longer neck! And so on and so forth until eventually we got the modern giraffe.
You may recognize this as ridiculous, to say the least. If you dye your hair blonde (even if it does result in you having way more sex), that does not mean your children will be blonde. If you decide that pinky toes are superfluous and cut your pinky toes off, your children would still have ten toes. Acquired traits do not get passed on, genes do. That’s how Mendelian genetics works. Right?
Except that’s not right. It’s still mostly right, but it pains me to say that Lamarck may not have been such a dumbass after all. In comes epigenetics, or changes made to gene expression by environmental experience. OMG, you haven’t heard of it? It’s so hot right now. Everyone’s doing it.
Previously by Katie Bainbridge: The Vicious Cycle of Neglect
DISCLAIMER: Epigenetics is hella complicated. I wrote my thesis on it, and I still only barely understand it. I could go into a lot of detail about methylation and chromatin remodeling, but I would probably bore the hell out of you (and myself), and I don’t want you to leave, so instead I’ll give you a simile I once heard in Cancer Cytopathology: Genes are like a recipe in a cook book, and epigenetics are like the notes you put in the margins as you use the recipe. When you photocopy that page, the original recipe will still be there, but so will all of the changes you made along the way.
So: epigenetics controls the expression of DNA. It permits genetically identical cells to express a huge variety of phenotypes. Think about it: every single cell in your body has the same genetic information in it, and yet they all do vastly different and specialized tasks. What makes a skin cell a skin cell and a neuron a neuron? Methylation and chromatin remodeling, that’s what. Obviously the vast majority of this takes place during in-utero development, but what we’re realizing now is that this process happens throughout your life and has some crazy effects on who you are genetically.
Remember those mice with the terrible mothers I mentioned in my last post? In a similar study by Dr. Meaney et al, they found that baby mice of highly affectionate mothers had less a methylated glucocorticoid receptor in the hippocampus. That sounds super complicated, I know, but it basically means that they handled stress better later in life. Having an attentive, caring mother changed the genetic expression in these baby mice, which in turn made them less fearful and anxious as adults. This effect happened regardless of whether or not the mice were raised by their biological mother or a foster mother. So these are genetic changes made by a purely environmental factor.
So here’s the part where epigenetics bends Mendelian inheritance over a table and has its way with it: there is evidence that some of these changes may even be passed on to offspring. Meaning Lamarck was right. Kind of. Getting a boob job does not mean your daughters will have big tits, but some acquired characteristics may be passed on to your children.
For example, an epidemiology study of the Överkalix region in Sweden showed that if a paternal grandfather lived through a famine in the years immediately preceding puberty, his grandchildren were at a much lower risk of developing diabetes and cardiovascular disease. If the grandfather grew up during a big harvest year, and thus had surplus of food, cardiovascular disease and diabetes in his grandchildren were more common. It didn’t matter if the grandchildren had never been to Sweden. The grandchildren could have never even met their grandfather; the effect was the same. Let me just repeat that because I don’t think you’re grasping how earth-shattering this is: an environmental condition was imprinted on the genes and passed on to the next generation. This isn’t a genetic predisposition to diabetes, this is a behavioral action that has lasting consequences for generations to come. If your gramps pigged out a lot between the ages of eight and 12, you have a shorter life expectancy. What an asshole.
There’s a specific window of time in which the environment can leave a transgenerational mark on genes, where ‘nurture can turn into ‘nature.’ Notice how the above study specifies the age range as “immediately preceding puberty?” It’s because that’s when little boys start making their gametes (or jizz, if you want to be blunt about it. Which I do). In the maternal line, transgenerational effects only seem to occur when a female fetus is in utero, since girls make their gametes while they’re still fetuses.
This discovery has amazing implications for drug research, particularly in areas like cancer and psychiatric disease. Imagine if we could develop a targeted epigenetic drug that could “lock” a gene that is just one exposure to asbestos away from turning on a cancer-factory in your lungs. Sure, it wouldn’t be a cure for cancer, per se… more like an immunity. Whatever, I’ll take what I can get.
But in the meantime, it seems like this column is starting to develop a theme of “unexpected ways your family screwed you.” Sorry about that.
To learn more about epigenetics I highly recommend the short documentary The Ghost in your Genes or download my forthcoming ebook on epigenetics and schizophrenia next week (which goes into considerably more detail but also contains considerably less jokes).
G. Kaati, L. O. Bygren, & S. Edvinsson (2002). Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period European Journal of Human Genetics (10), 682-688 DOI: 10.1038/sj.ejhg.5200859