The ENCODE (Encyclopedia Of DNA Elements) project received quite a bit of attention when its results were publicized last year. This project involved a very large consortium of scientists with the goal to identify all the functional elements in the human genome. In September 2012, 30 papers were published in a coordinated release and their extraordinary claim was that roughly 80% of the human genome was “functional”. This was in direct contrast to the prevailing view among molecular biologists that the bulk of human DNA was just “junk DNA”, i.e. sequences of DNA for which one could not assign any specific function. The ENCODE papers contained huge amounts of data, collating the work of hundreds of scientists who had worked on this for nearly a decade. But what garnered most attention, among scientists, the media and the public was the “80%” claim and the supposed “death of junk DNA“.

Soon after the discovery of DNA, the primary function ascribed to DNA was its role as a template from which messenger RNA could be transcribed and then translated into functional proteins. Using this definition of “function”, only 1-2% of the human DNA would be functional because they actually encoded for proteins. The term “junk DNA” was coined to describe the 98-99% of non-coding DNA which appeared to primarily represent genetic remnants of our evolutionary past without any specific function in our present day cells.

However, in the past decades, scientists have uncovered more and more functions for the non-coding DNA segments that were previously thought to be merely “junk”. Non-coding DNA can, for example, act as a binding site for regulatory proteins and exert an influence on protein-coding DNA. There has also been an increasing awareness of the presence of various types of non-coding RNA molecules, i.e. RNA molecules which are transcribed from the DNA but not subsequently translated into proteins. Some of these non-coding RNAs have known regulatory functions, others may not have any or their functions have not yet been established.

Despite these discoveries, most scientists were in agreement that only a small fraction of DNA was “functional”, even when all the non-coding pieces of DNA with known functions were included. The bulk of our genome was still thought to be non-functional. The term “junk DNA” was used less frequently by scientists, because it was becoming apparent that we were probably going to discover even more functional elements in the non-coding DNA.

In September 2012, everyone was talking about “junk DNA” again, because the ENCODE scientists claimed their data showed that 80% of the human genome was “functional”. Most scientists had expected that the ENCODE project would uncover some new functions for non-coding DNA, but the 80% figure was way out of proportion to what everyone had expected. The problem was that the ENCODE project used a very low bar for “function”. Binding to the DNA or any kind of chemical DNA modification was already seen as a sign of “function”, without necessarily proving that these pieces of DNA had any significant impact on the function of a cell.

The media hype with the “death of junk DNA” headlines and the lack of discussion about what constitutes function were appropriately criticized by many scientists, but the recent paper by Dan Graur and colleagues “On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE” has grabbed everyone’s attention. Not necessarily because of the fact that it criticizes the claims made by the ENCODE scientists, but because of the sarcastic tone it uses to ridicule ENCODE.

There have been so many other blog posts and articles that either praise or criticize the Graur paper, so I decided to list some of them here:

1. PZ Myers writes “ENCODE gets a public reaming” and seems to generally agree with Graur and colleagues.

2. Ashutosh Jogalekar says Graur’s paper is a “devastating takedown of ENCODE in which they pick apart ENCODE’s claims with the tenacity and aplomb of a vulture picking apart a wildebeest carcass.”

3. Ryan Gregory highlights some of the “zingers” in the Graur paper

Other scientists, on the other hand, agree with some of the conclusions of the Graur paper and its criticism of how the ENCODE data was presented, but disagree with the sarcastic tone:

1. OpenHelix reminds us that this kind of “spanking” should not distract from all the valuable data that ENCODE has generated.

2. Mick Watson shows how Graur and colleagues could have presented their key critiques in a very non-confrontational manner and foster a constructive debate.

3. Josh Witten points out the irony of Graur accusing ENCODE of seeking hype, even though Graur and his colleagues seem to use sarcasm and ridicule to also increase the visibility of their work. I think Josh’s blog post is an excellent analysis of the problems with ENCODE and the problems associated with Graur’s tone.

On Twitter, I engaged in a debate with Benoit Bruneau, my fellow Scilogs blogger Malcolm Campbell and Jonathan Eisen and I thought it would be helpful to share the Storify version here. There was a general consensus that even though some of the points mentioned by Graur and colleagues are indeed correct, their sarcastic tone was uncalled for. Scientists can be critical of each other, but can and should do so in a respectful and professional manner, without necessarily resorting to insults or mockery.

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Graur D, Zheng Y, Price N, Azevedo RB, Zufall RA, & Elhaik E (2013). On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE. Genome biology and evolution PMID: 23431001