Here's the abstract of the original paper published in Nature in September 2012 (Birney et al. 2012). Manolis Kellis (see below) is listed as a principle investigator and member of the steering committee.
The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.Most people reading this picked up on the idea that 80% of the genome had a function.
Here's a video produced by Nature. It features Senior Editor Magdalena Skipper and ENCODE Consortium PR frontman Ewan Birney. Pay attention to what Magdalena Skipper says at 2:24 and decide for yourself whether she thinks most of our genome is junk. (I assume that Ewan Birney approved this video.) It looks like hype to me.
Here's an article published on Sept. 5, 2012 by Nature writer Brendan Maher: ENCODE: The human encyclopaedia.
After an initial pilot phase, ENCODE scientists started applying their methods to the entire genome in 2007. Now that phase has come to a close, signalled by the publication of 30 papers, in Nature, Genome Research and Genome Biology. The consortium has assigned some sort of function to roughly 80% of the genome, including more than 70,000 ‘promoter’ regions — the sites, just upstream of genes, where proteins bind to control gene expression — and nearly 400,000 ‘enhancer’ regions that regulate expression of distant genes (see page 57)1. But the job is far from done, says Birney, a computational biologist at the European Molecular Biology Laboratory’s European Bioinformatics Institute in Hinxton, UK, who coordinated the data analysis for ENCODE. He says that some of the mapping efforts are about halfway to completion, and that deeper characterization of everything the genome is doing is probably only 10% finished. A third phase, now getting under way, will fill out the human instruction manual and provide much more detail.It's hard to read that any other way than saying that 80% of our genome has a function and very little is junk. We now know that's wrong and Nature was colluding with the ENCODE Consortium to hype the results.
Speaking of hype. Ryan Gregory collected a bunch of articles on the ENCODE results from September 2012. Almost all of the focus is on the idea that junk DNA has been debunked. Many of them contain quotations from ENCODE Consortium leaders reinforcing that claim. [The ENCODE media hype machine]. My favorites are Elizabeth Pennisi's article in Science where she declares the end of junk DNA [ENCODE Project Writes Eulogy for Junk DNA] and where she devotes a special feature to Ewan Birney [Genomics' Big Talker].
Here's how Ed Yong reported on the ENCODE papers back in September 2012. Ed Yong is an excellent science writer. It's not likely that he would misquote or misrepresent the views of Ewen Birney and Tom Gingeras.
According to ENCODE’s analysis, 80 percent of the genome has a “biochemical function”. More on exactly what this means later, but the key point is: It’s not “junk”. Scientists have long recognised that some non-coding DNA probably has a function, and many solid examples have recently come to light. But, many maintained that much of these sequences were, indeed, junk. ENCODE says otherwise. “Almost every nucleotide is associated with a function of some sort or another, and we now know where they are, what binds to them, what their associations are, and more,” says Tom Gingeras, one of the study’s many senior scientists.I suppose it's possible that all these journalists misunderstood what the ENCODE Consortium leaders were saying about function and junk. On the other hand, I suppose it's also possible that most of the journalists got it right. One thing is very clear. Nature blew it.
And what’s in the remaining 20 percent? Possibly not junk either, according to Ewan Birney, the project’s Lead Analysis Coordinator and self-described “cat-herder-in-chief”. He explains that ENCODE only (!) looked at 147 types of cells, and the human body has a few thousand. A given part of the genome might control a gene in one cell type, but not others. If every cell is included, functions may emerge for the phantom proportion. “It’s likely that 80 percent will go to 100 percent,” says Birney. “We don’t really have any large chunks of redundant DNA. This metaphor of junk isn’t that useful.”
Now we've got a peculiar situation. With the publication of their latest paper (Kellis et al., 2014) the ENCODE Consortium is pretending that they didn't mean it after all. It's all a big misunderstanding.
An anonymous writer at Nature picks up on the story [ENCODE debate revived online]. Here's how he/she describes the current situation ...
In the social-media age, scientific disagreements can quickly become public — and vitriolic. A report from the ENCODE (Encyclopedia of DNA Elements) Project consortium proposes a framework for quantifying the functional parts of the human genome. It follows a controversial 2012 Nature paper by the same group that concluded that 80% of the genome is biochemically functional (Nature 489, 57–74; 2012). Dan Graur, who studies molecular evolutionary bioinformatics at the University of Houston in Texas and is a vocal ENCODE critic, weighed in on this latest report. ENCODE's “stupid claims” from 2012 have finally come to back to “bite them in the proverbial junk”, Graur wrote on his blog. The targets noticed. “Some people seek attention through hyperbole and mockery,” says the report's first author Manolis Kellis, a computer scientist at the Massachusetts Institute of Technology in Cambridge. “We should stay focused on the issues.”
Kellis says that ENCODE isn't backing away from anything. The 80% claim, he says, was misunderstood and misreported. Roughly that proportion of the genome might be biochemically active, he explains, but some of that activity is undoubtedly meaningless, leaving unanswered the question of how much of it is really 'functional'. Kellis also argues that focusing on the portion of the genome that is shaped by natural selection can be misleading. For example, he says, genes that cause Alzheimer's disease or other late-in-life disorders may be largely immune to evolutionary pressure, but they are still definitely functional.If the ENCODE Consortium leaders really meant something different that what was being reported in the media then they should have spoken up loud and clear in September 2012. They should have disavowed all the quotations that were attributed to them and they should have made it very clear that their results did not mean the end of junk DNA.
But I don't believe for a second that the 80% claim was misunderstood and misreported. I believe that most Consortium leaders really believed that there was almost no junk in our genome. I think most of them still believe this.
But there's another issue. No matter how you look at it, Nature was wrong. Either they were wrong because most of our genome is junk (as I believe) or they were wrong because they misrepresented the ENCODE results (as Kellis claims).
I wonder when we can expect an apology and a retraction from Nature? Or Science?
(Not holding my breath ....)
[Hat Tip: Dan Graur: Misunderstanding & Misreporting? Perjury? An NP_Complete Problem?]
Birney et al. (The ENCODE Consortium) 2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74. [doi: 10.1038/nature11247]
Kellis, M. et al. (2014) Defining functional DNA elements in the human genome. Proc. Natl. Acad. Sci. (USA) April 24, 2014 published online [doi: 10.1073/pnas.1318948111 ]