Ewan BIrney
Image: John Spinks
In Brief
WHO
Ewan Birney
VOCATION | AVOCATION
“Cat herder in chief” of the ENCODE consortium of 400 geneticists from around the world
WHERE
European Bioinformatics Institute, Cambridge, England
RESEARCH FOCUS
Creating an encyclopedia detailing what the most mysterious parts of the human genome do
BIG PICTURE
“I get this strong feeling that previously I was ignorant of my own ignorance, and now I understand my ignorance.”
More In This Article
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Overview
Voices of ENCODE [Video]
In the 1970s, when biologists first glimpsed the landscape of human genes, they saw that the small pieces of DNA that coded for proteins (known as exons) seemed to float like bits of wood in a sea of genetic gibberish. What on earth were those billions of other letters of DNA there for? No less a molecular luminary than Francis Crick, co-discoverer of DNA’s double-helical structure, suspected it was “little better than junk.”
The phrase “junk DNA” has haunted human genetics ever since. In 2000, when scientists of the Human Genome Project presented the first rough draft of the sequence of bases, or code letters, in human DNA, the initial results appeared to confirm that the vast majority of the sequence—perhaps 97 percent of its 3.2 billion bases—had no apparent function. The “Book of Life,” in other words, looked like a heavily padded text.
Now, in a series of papers published in September in Nature (Scientific American is part of Nature Publishing Group) and elsewhere, the ENCODE group has produced a stunning inventory of previously hidden switches, signals and sign posts embedded like runes throughout the entire length of human DNA. In the process, the ENCODE project is reinventing the vocabulary with which biologists study, discuss and understand human inheritance and disease.
Ewan Birney, 39, of the European Bioinformatics Institute in Cambridge, England, led the analysis by the more than 400 ENCODE scientists who annotated the genome. He recently spoke with Scientific American about the major findings. Excerpts follow.
Scientific American: The ENCODE project has revealed a landscape that is absolutely teeming with important genetic elements—a landscape that used to be dismissed as “junk DNA.” Were our old views of how the genome is organized too simplistic?
BIRNEY: People always knew there was more there than protein-coding genes. It was always clear that there was regulation. What we didn’t know was just quite how extensive this was.
Just to give you a sense here, about 1.2 percent of the bases are in protein-coding exons. And people speculated that “maybe there’s the same amount again involved in regulation or maybe a little bit more.” But even if we take quite a conservative view from our ENCODE data, we end up with something like 8 to 9 percent of the bases of the genome involved in doing something like regulation.
Thus, much more of the genome is devoted to regulating genes than to the protein-coding genes themselves?
And that 9 percent can’t be the whole story. The most aggressive view of the amount we’ve sampled is 50 percent. So certainly it’s going to go above 9 percent, and one could easily argue for something like 20 percent. That’s not an unfeasible number.
Should we be retiring the phrase “junk DNA” now?
Yes, I really think this phrase does need to be totally expunged from the lexicon. It was a slightly throwaway phrase to describe very interesting phenomena that were discovered in the 1970s. I am now convinced that it’s just not a very useful way of describing what’s going on.
What is one surprise you have had from the “junk”?
There has been a lot of debate, inside of ENCODE and outside of the project, about whether or not the results from our experiments describe something that is really going on in nature. And then there was a rather more philosophical question, which is whether it matters. In other words, these things may biochemically occur, but evolution, as it were, or our body doesn’t actually care.
That debate has been running since 2003. And then work by ourselves, but also work outside of the consortium, has made it much clearer that the evolutionary rules for regulatory elements are different from those for protein-coding elements. Basically the regulatory elements turn over a lot faster. So whereas if you find a particular protein-coding gene in a human, you’re going to find nearly the same gene in a mouse most of the time, and that rule just doesn’t work for regulatory elements.
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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.