The case of "junk DNA" and why it shouldn't be called junk: Epigenetics.

(This is part 3 of 4 in a series dedicated to "junk DNA". Links to the previous parts: Part 1, and Part 2.)

Last year I was diagnosed with thyroid disease. Despite feeling pretty crappy, I found the phenomenon extremely fascinating. Okay, I'll admit, I found it fascinating after my doc told me worst case scenario they'd remove the thyroid and I'd be as good as new (minus the thyroid, that is). Here's what happened: somehow, my immune system decided that my thyroid was some kind of foreign object that did not belong, and it started producing antibodies to destroy it. And I mean literally destroy it: left untreated, the antibodies will keep attacking the thyroid until it's gone.

How the immune systems knows "self" from "non-self" (and hence attacks foreign objects but, under normal conditions, not its own cells) is a fascinating topic and worth a post in itself (and I promise it'll come, just give me a few more weeks!).

For now, though, I want to focus on this: thyroid disease is a purely genetic disease. So, if it was encoded in my DNA, why did I end up getting it last year instead of having it since birth?

Epigenetics  holds the answer to my question (for the veterans in the field, please see my note below).

There was a nice article in the Time magazine a few months ago that described the concept really well: if you compare our body to a computer, genetics is the hardware and epigenetics is the software. Or, to use another analogy that my friend and fellow scientist/writer Ian Tregillis coined, if the genome is a four-note musical score, then the epigenome is the musician who interprets and executes the music.

"Epigenetics" is an umbrella term that encompasses all processes that regulate gene expression. In other words, what decides which genes are "turned on" and which are "turned off."

Think of en encrypted message. You don't know the meaning of the message until I give you the key. Depending on what key I give you, the message may change dramatically. DNA is the encrypted message. In order to "read" the message, i.e. the instructions on how to make proteins, we need a system capable of "translating" the message. It's a very delicate and complex system. And while our DNA is exactly the same in every cell of our body, the epigenetics is different.

Well, that's kind of obvious, isn't it? Think about it: how does a brain cell know to behave like a brain cell, and a skin cell to behave like a skin cell? After all, they have the same DNA. What differentiates them is the epigenetic processes that translate the DNA in each type of cell. The brain cell will have "brain genes" activated, and the skin cell will have the "skin genes" activated, while the others will be turned off.

So far so good. Still, how do you explain genetic diseases like diabetes showing up in adults rather than from birth? They are indeed encoded in the individual's DNA, but in a very subtle way. Mutations that sit there, waiting to go off. Waiting for the right change in the epigenetic process that will suddenly activate them.

Yes, that's exactly what happens: our DNA stays the same throughout our lifetime, but the way we express the genes can and does in fact change. Environmental stress is one of the major reasons affecting these changes [1]. Example: drought can cause certain plants to switch on pseudogenes regulating their capability of survival with less water [2]. The availability of food can induce analogous epigenetic changes in animals. Studies have shown that a pregnant woman's diet can activate pseudogenes not only on the baby, but the changes are actually inherited by the baby's babies as well [3]. Even though these are not genetic changes, hence they do not alter the DNA, still, they are in fact inheritable and it takes a few generations for the switches in gene expression to wear off [4].

So, think about it: (1) DNA doesn't quite dictate who or what we are. And (2) good ol' Lamarck was not so far from the truth after all, was he?

Back to my original question: thyroid disease was indeed "encoded" in my genome, but it was an epigenetic change in the way my genes were expressed that one day set my immune system off to an anti-thyroid mission.

What does this have to do with junk DNA?

Well, remember what junk DNA really is: it's non-coding DNA. Genes that are "turned off." But wait, we just learned that "turned off" or "turned off" is something that can change during one's lifespan. So, what we call "junk DNA" is something dynamical, something that when we look again tomorrow may have suddenly become functional because of the way DNA gets translated.

More and more studies are finding a link between cancer and mutations that sit in pseudogenes (non-functional genes that are part of the so-called junk DNA). At first this was quite surprising. If these genes aren't translated, how can they affect our body? Well, it turns out they are indeed expressed in cancer patients, giving origin to the term oncogene. In other words, the mutation is there, and it's not until an epigenetic change occurs and the pseudogene gets activated, that the disease takes off.

So, don't call non-coding DNA junk.

We need to study this part of our DNA, because it holds important information about our health. It also holds the key to our survival as a species by allowing us to adapt and change as the environment around us changes. And, finally, it holds our evolutionary history: we carry our ancestors, from viruses to bacteria to monkeys in our DNA.

Technical note: I am using the term "epigenetics" in a broad way, to include any of the following scenarios: post-replication DNA changes; post-transcription RNA changes; and, finally, changes in protein translation. The association between thyroid disease and epigenetics is purely my own, but an analogous conclusion has been reached for similar autoimmune disorders, where the immune systems fails to recognize self from non-self -- see this paper.   

REFERENCES:
[1] Inheritance of Stress-Induced, ATF-2-Dependent Epigenetic Change. Ki-Hyeon Seong, Dong Li, Hideyuki Shimizu, Ryoichi Nakamura, Shunsuke Ishii. Cell - 24 June 2011 (Vol. 145, Issue 7, pp. 1049-1061)

[2] Epigenetics in the extreme: prions and the inheritance of environmentally acquired traits. Halfmann R, and Lindquist S. Science. 2010 Oct 29;330(6004):629-32.

[3] Epigenomic disruption: the effects of early developmental exposures. Bernal AJ, Jirtle RL. Birth Defects Res A Clin Mol Teratol. 2010 Oct;88(10):938-44.

[4] Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution. Eva Jablonka and Gal Raz, The Quarterly Review of Biology. Vol. 84, No. 2 (June 2009), pp. 131-176

Picture: Rock. Canon 40D, focal length 85mm, exposure time 1/100.