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.
This article was originally published with the title Journey to the Genetic Interior.
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8 Comments
Add CommentI always had a feeling that “Junk DNA” is not junk at all. If you look at computer “.exe” file with code browser you will find some subroutines and a lot of data between them. Subroutines can be easily decoded and understood but data looks like a junk unless you know its origin – a picture, a sound, etc.
Reply | Report Abuse | Link to thisI forwarded this article to a colleague who works on the basic structures of organic entities and he replied (summary of my translation): "Isn't it strange that until very recently it was believed that only 20% of the genes were useful, these being mostly the genes that produced proteins, which would be roughly the equivalent of bosons producing mass (Higgs) and that the rest of the genes was considered junk, whereas in physics they know what 80% of the stuff is for except that they can't figure out what exactly produces mass? I was proposing to think along those lines three years ago and nobody wanted to even consider the idea (or did a few and never told me?). And look at this now."
Reply | Report Abuse | Link to thisI should add his POV is that if physics is nature's hardware then biology is its software and that we should see each as the two sides of the same coin. Maybe he is right when he says he has a ten-year headstart on elementary research and that he suffers not so much from social comparision bias but from reviewers' tunnelvision?
Amusing also that dark matter is said to be about 80% of all matter.
Reply | Report Abuse | Link to thisPresumably this is why the erstwhile junk is "now often referred to as the dark matter." (http://www.nytimes.com/2012/09/06/science/far-from-junk-dna-dark-matter-proves-crucial-to-health.html?pagewanted=all)
yes, congrats... you've managed to discover what many other researchers could have told you ten years ago.
Reply | Report Abuse | Link to thisI have suspected for a long time that this so-called 'Junk DNA' (present in ALL living organisms) is actually 'Gaia DNA'. There definitely is some co-ordinating mechanism that regulates the biosphere of this planet. What more obvious place could it be?!?!
Reply | Report Abuse | Link to thisWe are FAR MORE than just the sum of our parts!
http://blogs.nature.com/news/2012/09/fighting-about-encode-and-junk.html
Reply | Report Abuse | Link to thisBirney concurs with deprecating the term "junk DNA", but is conservative on how much non-protein-coding DNA may be functional ("between 9 and 80 per cent"). The fact that the entire genome is copied at every cell division suggests that close to 100% of DNA must be functional. Had any significant portion of DNA been non-functional in the past, evolutionary pressure to evolve an editing-out mechanism, and thus increase the cell’s energy efficiency, would have been tremendous: cells that could do this would dominate the biosphere. It is a reasonable assumption that, if such editing had ever been needed, then it would have arisen and would continue to operate, leaving only functional DNA.
Reply | Report Abuse | Link to thisBirney also uses the conservative term "regulation" to describe how the 98.8% of non-protein-coding DNA interacts with the 1.2% of protein-coding segments. A more useful terminology is to describe the entire genome as software – instructions for cells to build copies of themselves and, in multicellular lifeforms, assemble cells into lifeforms. In this view, the protein-coding segments are thought of as fixed-value strings within the code – a more useful initial hypothesis.
If we could send a personal computer back in time to Alan Turing, loaded with an application like Microsoft Excel and with a copy of the sourcecode, it seems unlikely that, on comparing the screen output with the sourcecode, Turing would conclude that fixed values in the code like "File", "Edit", and "View" were the essence of the software and that the other 99% merely "regulates" the operation of the fixed values when they are transcribed to the screen.
Instead of "regulatory elements" why not use the name Metagenes since they regulate genes? The turing machine analogy works well. Protein encoding genes are the constants in the system and the Metagenes control which constants get read via the transcription proteins and the exon / intron RNA selection processes and all the incredibly complex feedback mechanisms which regulate the supply and demand processes within the cell machinery not to mention the messaging which goes no between neighbouring cells and environmental response mechanisms!!!!!!
Reply | Report Abuse | Link to thisMy guess is that we will discover a complex hierarchy or Metagenes similar to the hierarchy of the hormonal control and regulatory system.