Hidden Treasures in Junk DNA

What was once known as junk DNA turns out to hold hidden treasures, says computational biologist Ewan Birney

Now that we are retiring the phrase “junk DNA,” is there another, better metaphor that might explain the emerging view of the genetic landscape?
What it feels like is genuinely a jungle—a completely dense jungle of stuff that you have to work your way through. You’re trying to hack your way to a certain position. And you’re really not sure where you are, you know? It’s quite easy to feel lost in there.

Over the past 20 years the public has been repeatedly told that these big genomic projects—starting with the Human Genome Project and going on through various other projects—were going to explain everything we needed to know about the “book of life.” Is ENCODE simply the latest in this sequence?
I think that each time we always said, “These are foundations. You build on them.” Nobody said, “Look, the human genome bases, that’s it. It’s all done and dusted—we’ve just got a bit of code breaking to do here.” Everybody said, “We’re going to be studying this for 50 years, 100 years. But this is the foundation that we start on.” I do get the feeling that the ENCODE project is the next layer in that foundational resource for other people to stand on top of and look further. The biggest change here is in our list of known unknowns. And I think people should understand that although finding out how much you don’t know can feel regressive and frustrating, identifying the gaps is really good.

Ten years ago we didn’t know what we didn’t know. There is no doubt that ENCODE poses many, many, many more questions than it directly answers. At the same time, for Crohn’s disease, say, and lots of other things, there are some effectively quick wins and low-hanging fruit—at least for researchers—where you start to say to people, “Oh my gosh, have you looked there?”

It’s just one more step. It’s an important step, but nowhere near the end, I’m afraid.

You sometimes refer to yourself as ENCODE’s “cat herder in chief.” How many people were involved in the consortium, and what was it like coordinating such a massive effort?
This is very much a different way of doing science. I am only one of 400 investigators, and I am the person who is charged to make sure that the analysis was delivered and that it all worked out. But I had to draw on the talents of many, many people.

So I’m more like the cat herder, the conductor, necessarily, than someone whose brain can absorb all of this. It comes back to that sense that it’s a bit of a jungle out there.

Well, you deserve a lot of credit. It’s more than just cats. They’re pretty opinionated cats.
Yeah, they are. What scientists are not are dogs. Dogs naturally run in packs. Cats? No. And I think that sums up the normal scientific phenotype. And so you have to cajole these people sometimes into sort of taking the same direction.

Do you see a point where all this complex information will resolve into a simpler message about human inher­itance and human disease? Or do we have to accept the fact that complexity is, as it were, in our DNA?
We are complex creatures. We should expect that it’s complex out there. But I think we should be happy about that and maybe even proud about it.

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This article was originally published with the title "Journey to the Genetic Interior."

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