Intelligent Design Creationists Choose ENCODE Results as the #1 Evolution Story of 2012

The folks over at Evolution News & Views (sic) have selected the ENCODE papers as the Number 1 evolution-related story of 2012. Naturally, they fell for the hype of the ENCODE/Nature publicity campaign as you can see from the blog title: Our Top 10 Evolution-Related Stories: #1, ENCODE Project Buries "Junk DNA".

Most of the article is just the reposting of an article by Casey Luskin but some anonymous editor has added ...

Editor's note: For the No. 1 slot among evolution-related news stories of 2012, this one was an easy pick. The publication of the ENCODE project results detonated what had been considered among the sturdiest defenses that Darwinian evolutionary theory could still fall back upon: "Junk DNA." Casey Luskin's initial reporting is featured below. See also our response to the ensuing controversy over ENCODE ("Why the Case for Junk DNA 2.0 Still Fails").

Normally I would make fun of the creationists for misunderstanding the real scientific results in the papers that were published last September but, in this case, there are lots of real scientists who fell into the same trap.

Even Science magazine selected the ENCODE results as a top-ten breakthrough and noted that 80% of the human genome now has a function [Science Magazine Chooses ENCODE Results as One of the Top Ten Breakthroughs in 2012]. Oh well, I guess I'll just have to be content to point out that many scientists are as stupid as many Intelligent Design Creationists!

I can still mock the creationists for claiming that "Darwinian evolutionary theory" supports junk DNA.

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Science Writes Eulogy for Junk DNA

Elizabeth Pennisi is a science writer for Science, the premiere American science journal. She's been writing about "dark matter" for years focusing on how little we know about most of the human genome and ignoring all of the data that says it's mostly junk [see SCIENCE Questions: Why Do Humans Have So Few Genes? ].

It doesn't take much imagination to guess what Elizabeth Pennisi is going to write when she heard about the new ENCODE Data. Yep, you guessed it. She says that the ENCODE Project Writes Eulogy for Junk DNA.

THEME

Genomes & Junk DNALet's look at the opening paragraph in her "eulogy."

When researchers first sequenced the human genome, they were astonished by how few traditional genes encoding proteins were scattered along those 3 billion DNA bases. Instead of the expected 100,000 or more genes, the initial analyses found about 35,000 and that number has since been whittled down to about 21,000. In between were megabases of “junk,” or so it seemed.

Scientific American Chooses ENCODE Project as One of the Top Ten Science Stories in 2012

It's pretty hard to ignore the ENCODE papers if you're selecting the top ten science stories of 2012. This doesn't mean it's a "breakthrough" as Science magazine claims [Science Magazine Chooses ENCODE Results as One of the Top Ten Breakthroughs in 2012]. And it doesn't mean that the results overthrow Darwinian evolutionary theory as implied by the Intelligent Design Creationists [Intelligent Design Creationists Choose ENCODE Results as the #1 Evolution Story of 2013].

The Scientific American article was written by Bora Zivkovic, a long-time blogger who knows the difference between hype and reality. He apparently knows which scientists to believe and which ones to ignore [The Top 10 Science Stories of 2012: Publication of the ENCODE Encyclopedia: A Milestone in Genome Research].

Unfortunately, much of the discussion surrounding the publication of ENCODE failed to focus on the usefulness of the catalogue and the techniques that built it. Instead, much of the debate centered on the failure to understand that transcription does not necessarily imply meaningful biological function. Cells are messy biological entities, with lots of gunk and goo floating around, so mistakes happen all the time. Many DNA sequences get translated into RNA, only to have the cell degrade that RNA. Much, perhaps most, of the DNA in our genomes—despite being occasionally transcribed, and thus recorded in ENCODE—is still functionless “junk DNA.” That is actually not surprising; it is in fact expected from evolutionary theory. Thanks to ENCODE, though, we should eventually learn which sequences are the junk and which are the gems of cell activity.

This is a very different take on the subject than that published by the editors of Science and the Intelligent Design Creationists.

I wonder why?

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Ewan Birney: Genomics' Big Talker

My copy of Science arrived in the mail last week and I wasn't surprised to see the article by Elizabeth Pennisi on ENCODE Project Writes Eulogy for Junk DNA. Pennisi has long been skeptical about junk DNA. She advocates the position that what makes us human is hidden in the "dark matter" of the genome. She has never lost an opportunity to promote those scientists who claim to have discovered function in junk DNA so it was natural for her to fall hook-line-and-sinker for the recent ENCODE publicity campaign [see Science Writes Eulogy for Junk DNA].

What did surprise me was a three-page spread on Ewan Birney: Genomics' Big Talker, written by Elizabeth Pennisi. This is extraordinary. I don't know of another example where a leading science journal has promoted a young scientist in this manner. Of course, it's doubly extraordinary because, in this case, Science is promoting a scientist who just made some serious mistakes interpreting his own data! The man who is so prominently featured in the Sept. 7, 2012 issue of Science magazine is coming under serious criticism for letting publicity rule his science. He has almost single-handedly¹ damaged the reputation of 400 scientists in the ENCODE Consortium and he did it, in part, because he was not knowledgeable about his own field of expertise! [see ENCODE Leader Says that 80% of Our Genome Is Functional and The ENCODE Data Dump and the Responsibility of Scientists]

UPDATE:A reader has reminded me that Science published two pages (online) on Felicia Wolfe-Simon at the time of the arsenic affair. Hmmmm ... is this the beginning of a pattern?

Chapter 9: The ENCODE Publicity Campaign

In September 2012, the ENCODE researchers published a bunch of papers claiming to show that 80% of the human genome was functional. They helped orchestrate a massive publicity campaign with the help pf Nature— a campaign that succeeded in spreading the message that junk DNA had been refuted.

That claim was challenged within 24 hours by numerous scientists on social media. They pointed out that the ENCODE researchers were using a ridiculous definition of function and that they had completely ignored all the evidence for junk DNA. Over the next two years there were numerous scientific papers criticizing the ENCODE claims and the ENCODE researchers were forced to retract the claim that they had proven that 80% of the genome is functional.

I discuss what went wrong and lay the blame mostly on the ENCODE researchers who did not behave as proper scientists when presenting a controversial hypothesis. The editors of Nature share the blame for not doing a proper job of vetting the ENCODE claims and not subjecting the papers to rigorous peer review. Science writers also failed to think critically about the results they were reporting.

Click on this link to see more.
Chapter 9: The ENCODE Publicity Campaign

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The ENCODE Data Dump and the Responsibility of Scientists

A few hours ago I criticized science journalists for getting suckered by the hype surrounding the publication of 30 papers from the ENCODE Consortium on the function of the human genome [The ENCODE Data Dump and the Responsibility of Science Journalists].

They got their information from supposedly reputable scientists but that's not an excuse. It is the duty and responsibility of science journalists to be skeptical of what scientists say about their own work. In this particular case, the scientists are saying the same things that were thoroughly criticized in 2007 when the preliminary results were published.

I'm not letting the science journalists off the hook but I reserve my harshest criticism for the scientists, especially Ewan Birney who is the lead analysis coordinator for the project and who has taken on the role as spokesperson for the consortium. Unless other members of the consortium speak out, I'll assume they agree with Ewan Birney. They bear the same responsibility for what has happened.

Jonathan Wells illustrates zombie science by revisiting junk DNA

Jonathan Wells has written a new book (2017) called Zombie Science: More Icons of Evolution. He revisits his famous Icons of Evolution from 2000 and tries to show that nothing has changed in 17 years.

I wrote a book in 2000 about ten images images, ten "icons of evolution," that did not fit the evidence and were empirically dead. They should have been buried, but they are still with us, haunting our science classrooms and stalking our children. They are part of what I call zombie science.

I won't bore you with the details. The icons fall into two categories: (1) those that were meaningless and/or trivial in 2000 and remain so today, and (2) those that Wells misunderstood in 2000 and are still misunderstood by creationists today.

Philip Ball strikes back

Philip Ball believes that we are in the middle of a revolution in our way of thinking about how life works. His ideas are complex but part of his case involves molecular biology and how things work at the molecular level. Ball believes that the old view of molecular biology placed far too much emphasis on coding DNA and ignored all the other functional regions of genomes. He also says that most of our genes specify non-coding RNA instead of mRNA and implies to his readers that a very large fraction of our genome is functional (i.e. not junk).¹

In order to build the case for revolution, he tries to demonstrate a paradigm shift in our view of molecular biology by showing a huge gap between the understanding of previous generations of molecular biologists and the post-genomic view. I believe he is wrong about this for two reasons: first, he misrepresents the views of older molecular biologists and, second he misrepresents the discoveries of the past twenty years. I tried to explain why he was wrong about these two claims in a previous post where I discussed an article he published in Scientific American in May 2024: Philip Ball says RNA may rule our genome.

Philip Ball responded to my criticism in a comment under that article.

Older molecular biologists were really stupid

I said ...

Ball begins with the same old myth that writers like him have been repeating for many years. He claims that before ENCODE most molecular biologists were really stupid. According to Philip Ball, most of us thought that coding DNA was the only functional part of the genome and most of the rest was junk DNA.

In the comment section of my earlier post, Philip Ball says,

I’m sorry to say that Larry’s commentary here is dismayingly inaccurate.

Let’s get this one out of the way first:

“He claims that before ENCODE most molecular biologists were really stupid.”

I have never made this claim and never would – it is a pure fabrication on Larry’s part. I guess this is what John Horgan meant in his comment to Larry: credible writers don’t just make up stuff.

I admit that Philip Ball never said those exact words. I'll leave it to the readers to decide whether my characterization of his position is accurate.

I stand by the statements I made although I admit to a bit of hyperbole. Ball has said repeatedly that the molecular biologists of my generation were wedded to the idea that coding regions were the only important part of the genome and he often connects that to the Central Dogma of Molecular Biology. He also claims that the experts in molecular biology dismissed all non-coding DNA as junk. Here's how he puts it in another article that he published recently in Aeon: We are not machines.

Only around 1-2 per cent of the entire human genome actually consists of protein-coding genes. The remainder was long thought to be mostly junk: meaningless sequences accumulated over the course of evolution. But at least some of that non-coding genome is now known to be involved in regulating genes: altering, activating or suppressing their transcription in RNA and translation into proteins.

I interpret that to mean that older molecular biologists, like me, didn't know about functional non-coding DNAs such as centromeres, telomeres, origins of replication, non-coding genes, SARs, and regulatory sequences in spite of the fact that thousands of papers on these sequences were published in the 30 years that preceded the publication of the first draft of the human genome sequence. This is not true, we did know about those things. I don't think it's too much of an exaggeration to say that Philip Ball thinks we were really stupid.

Here's what he says in his book, "How Life Works" (p. 85) when he's talking about the beginning of the human genome project.

Even at its outset, it faced the somewhat troubling issue that just 2 percent or so of our genome actually accounts for protein-coding genes. The conventional narrative was that our biology was all about proteins, for each of which the genome held the template. ... But we had all this other DNA too! What was it for? The common view was that it was mostly just junk, like the stuff in our attics: meaningless material accumulated during evolution, which our cells had no motivation to clear out.

Again, his claim is that in 1990 at the beginning of the human genome project the experts in molecular biology thought that non-coding DNA was mostly junk (98% of the genome). I have repeatedly refuted this myth and challenged anyone to come up with a single scientific paper arguing that all non-coding DNA is junk. I challenge Philip Ball to find a single molecular biology textbook written before 1990 that fails to discuss regulation, non-coding genes, and other non-coding functional elements in the human genome.

The truth is that the molecular biology experts concluded in the 1970s that we had about 30,000 genes and that 90% of our genome is junk and 10% is functional. That 10% consisted of about 2% coding DNA (now thought to be only 1%) and 8% functional non-coding DNA. So the "conventional narrative" was that there was a lot more functional non-coding DNA than coding DNA.

The human genome is full of genes for regulatory RNAs.

"Ball is one of the most meticulous, precise science writers out there. He is the antithesis of hypey, "dumb-it-down" reporting. He is MUCH more credible than you are, Laurence."

John Horgan July, 2024The title of the article I was discussing is "Revolutionary Genetics Research Shows RNA May Rule Our Genome." In that article Ball says that ENCODE was basically right and there are many more non-coding genes than protein-coding genes. I pointed out that Ball mentions some criticism of this idea but only to dismiss it. I said that "[Ball] wants you to believe that almost of all of those transcripts are functional—that's the revolution that he's promoting." Philip Ball objects to this statement ...

This too is sheer fabrication. I don’t say this in my article, nor in my book. Instead, I say pretty much what Larry seems to want me to say, but for some reason he will not admit it – which is that there is controversy about how many of the transcripts are functional."

Ball states that "ENCODE was basically right" when they claimed that 75% of our genome was transcribed and he goes on to say that ...

Dozens of other research groups, scoping out activity along the human genome, also have found that much of our DNA is churning out 'noncoding' RNA.

He says that ENCODE has identified 37,000 noncoding genes but there may be as many as 96,000. After making these definitive statements, he mentions that there are "still doubters" but then discuss why these discoveries are revolutionary. Later on he quotes John Mattick suspecting that there may be more that 500,000 non-coding genes.

Toward the end of the article, after discussing all kinds of functional RNAs, he brings up the Ponting and Haerty review where they say that most lncRNAs are just noise. He also mentions that the low copy number of non-coding RNAs raises questions about whether they are functional but immediately counters with the standard excuses from his allies.

Ball closes the article with ...

Gingeras says he is perplexed by ongoing claims that ncRNAs are merely noise or junk, as evidence is mounting that they do many things. "It is puzzling why there is such an effort to persuade colleagues to move from a sense of interest and curiosity in the ncRNA field to a more dubious and critical one," he says.

Perhaps the arguments are so intense because they undercut the way we think our biology works. Ever since the epochal discovery about DNA's double helix and how it encodes information, the bedrock idea of molecular biology has been that there are precisely encoded instructions that program specific molecules for particular tasks. But ncRNAs seem to point to a fuzzier, more collective, logic to life. It is a logic that is harder to discern and harder to understand. ut if scientists can learn to live with the fuzziness, this view of life may turn out to be more complete.

What's remarkable about the quote from a leading ENCODE worker (Gingeras) is that he is "puzzled" by scientists who are dubious and critical about claims in the ncRNA field. Isn't that what good scientists are supposed to do? Isn't that exactly what we did when we successfully challenged the dubious claims about junk DNA made in 2012?

There is no doubt in my mind that Philip Ball has fallen hook-line-and-sinker for the ENCODE claims that our genome is buzzing with non-coding genes. He only brings up the counter-arguments to dismiss them and pretend that he is being fair. Nobody who was truly skeptical about the function of transcripts would write an article with the title, "Revolutionary Genetics Research Shows RNA May Rule Our Genome."

However, as Ball points out in other comments, he does have a sentence in his book where he mentions that perhaps only 30% of the genome is functional. He says in the comment that what he believes is that the amount of functional DNA lies somewhere between 10% and 30%. That's not something that he mentions in the Scientific American article but, if he's being honest, it does mean that I was unfair when I said he believes that "almost of all of those transcripts are functional" but I only know that from what he now says, not from the published article.

If I were to take Philip Ball at his word—as expressed in the comment—then he must believe that most of the ENCODE transcripts are junk RNA. That's not a belief that you get from reading his published work.² Furthermore, if I were to take him at his word, then he must believe that there are some reasonable criteria that must be applied to a transcript in order to decide whether it has a biologically relevant function. So, when he says that ENCODE identified 37,600 non-coding genes he must have these criteria in mind but he doesn't express any serious skepticism about that number. We all know that there's no solid evidence that such a large number of transcripts are functional but that doesn't bother Philip Ball. He thinks we are in the middle of an RNA revolution.

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1. In commenting to my previous post, Ball says he believes that somewhere between 70% and 90% of our genome is junk but he doesn't say this in the Scientific American article. Instead, he says that scientists were surprised to learn that 75% of the human genome is transcribed implying that there's a lot of function. He goes on the say that "ENCODE was basically right." But what the ENCODE publicity campaign actually said was that junk DNA is dead and there's practically no junk DNA. If Ball really believes that up to 90% of the genome is junk then to me this means that ENCODE was spectacularly wrong not "basically right."

2. Ball says that 75% of the genome is transcribed. If Ball believes that as little as 10% may be functional then he must believe that less than 10% is transcribed to produce functional RNAs since he has to allow for regulatory sequences and other functional DNA elements. Let's say that 8% is a reasonable number. Ball seems to be willing to admit that 67% of the genome might be transcribed to produce junk RNA.

Required reading for the junk DNA debate

This is a list of scientific papers on junk DNA that you need to read (and understand) in order to participate in the junk DNA debate. It's not a comprehensive list because it's mostly papers that defend junk DNA and refute arguments for massive amounts of function. The only exception is the paper by Mattick and Dinger (2013).¹ It's the only anti-junk paper that attempts to deal with the main evidence for junk DNA. If you know of any other papers that make a good case against junk DNA then I'd be happy to include them in the list.

If you come across a publication that argues against junk DNA, then you should immediately check the reference list. If you do not see some of these references in the list, then don't bother reading the paper because you know the author is not knowledgeable about the subject.

Brenner, S. (1998) Refuge of spandrels. Current Biology, 8:R669-R669. [PDF]

Brunet, T.D., and Doolittle, W.F. (2014) Getting “function” right. Proceedings of the National Academy of Sciences, 111:E3365-E3365. [doi: 10.1073/pnas.1409762111]

Casane, D., Fumey, J., et Laurenti, P. (2015) L’apophénie d’ENCODE ou Pangloss examine le génome humain. Med. Sci. (Paris) 31: 680-686. [doi: 10.1051/medsci/20153106023] [The apophenia of ENCODE or Pangloss looks at the human genome]

Cavalier-Smith, T. (1978) Nuclear volume control by nucleoskeletal DNA, selection for cell volume and cell growth rate, and the solution of the DNA C-value paradox. Journal of Cell Science, 34(1), 247-278. [doi: PDF]

Doolittle, W.F. (2013) Is junk DNA bunk? A critique of ENCODE. Proc. Natl. Acad. Sci. (USA) published online March 11, 2013. [PubMed] [doi: 10.1073/pnas.1221376110]

Doolittle, W.F., Brunet, T.D., Linquist, S., and Gregory, T.R. (2014) Distinguishing between “function” and “effect” in genome biology. Genome biology and evolution 6, 1234-1237. [doi: 10.1093/gbe/evu098]

Doolittle, W.F., and Brunet, T.D. (2017) On causal roles and selected effects: our genome is mostly junk. BMC biology, 15:116. [doi: 10.1186/s12915-017-0460-9]

Eddy, S.R. (2012) The C-value paradox, junk DNA and ENCODE. Current Biology, 22:R898. [doi: 10.1016/j.cub.2012.10.002]

Eddy, S.R. (2013) The ENCODE project: missteps overshadowing a success. Current Biology, 23:R259-R261. [10.1016/j.cub.2013.03.023]

Graur, D. (2017) Rubbish DNA: The functionless fraction of the human genome Evolution of the Human Genome I (pp. 19-60): Springer. [doi: 10.1007/978-4-431-56603-8_2 (book)] [PDF]

Graur, D. (2017) An upper limit on the functional fraction of the human genome. Genome Biology and Evolution, 9:1880-1885. [doi: 10.1093/gbe/evx121]

Graur, D., Zheng, Y., Price, N., Azevedo, R. B., Zufall, R. A., and 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 published online: February 20, 2013 [doi: 10.1093/gbe/evt028

Graur, D., Zheng, Y., and Azevedo, R.B. (2015) An evolutionary classification of genomic function. Genome Biology and Evolution, 7:642-645. [doi: 10.1093/gbe/evv021]

Gregory, T. R. (2005) Synergy between sequence and size in large-scale genomics. Nature Reviews Genetics, 6:699-708. [doi: 10.1038/nrg1674]

Haerty, W., and Ponting, C.P. (2014) No Gene in the Genome Makes Sense Except in the Light of Evolution. Annual review of genomics and human genetics, 15:71-92. [doi:10.1146/annurev-genom-090413-025621]

Hurst, L.D. (2013) Open questions: A logic (or lack thereof) of genome organization. BMC biology, 11:58. [doi:10.1186/1741-7007-11-58]

Kellis, M., Wold, B., Snyder, M.P., Bernstein, B.E., Kundaje, A., Marinov, G.K., Ward, L.D., Birney, E., Crawford, G. E., and Dekker, J. (2014) Defining functional DNA elements in the human genome. Proc. Natl. Acad. Sci. (USA) 111:6131-6138. [doi: 10.1073/pnas.1318948111]

Mattick, J. S., and Dinger, M. E. (2013) The extent of functionality in the human genome. The HUGO Journal, 7:2. [doi: 10.1186/1877-6566-7-2]

Five Things You Should Know if You Want to Participate in the Junk DNA DebateMorange, M. (2014) Genome as a Multipurpose Structure Built by Evolution. Perspectives in biology and medicine, 57:162-171. [doi: 10.1353/pbm.2014.000]

Niu, D. K., and Jiang, L. (2012) Can ENCODE tell us how much junk DNA we carry in our genome?. Biochemical and biophysical research communications 430:1340-1343. [doi: 10.1016/j.bbrc.2012.12.074]

Ohno, S. (1972) An argument for the genetic simplicity of man and other mammals. Journal of Human Evolution, 1:651-662. [doi: 10.1016/0047-2484(72)90011-5]

Ohno, S. (1972) So much "junk" in our genome. In H. H. Smith (Ed.), Evolution of genetic systems (Vol. 23, pp. 366-370): Brookhaven symposia in biology.

Palazzo, A.F., and Gregory, T.R. (2014) The Case for Junk DNA. PLoS Genetics, 10:e1004351. [doi: 10.1371/journal.pgen.1004351]

Rands, C. M., Meader, S., Ponting, C. P., and Lunter, G. (2014) 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage. PLOS Genetics, 10:e1004525. [doi: 10.1371/journal.pgen.1004525]

Thomas Jr, C.A. (1971) The genetic organization of chromosomes. Annual review of genetics, 5:237-256. [doi: annurev.ge.05.120171.001321]

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1. The paper by Kellis et al. (2014) is ambiguous. It's clear that most of the ENCODE authors are still opposed to junk DNA even though the paper is mostly a retraction of their original claim that 80% of the genome is functional.

The 20th anniversary of the human genome sequence: 6. Nature doubles down on ENCODE results

Nature has now published a series of articles celebrating the 20th anniversary of the publication of the draft sequences of the human genome [Genome revolution]. Two of the articles are about free access to information and, unlike a similar article in Science, the Nature editors aren't shy about mentioning an important event from 2001; namely, the fact that Science wasn't committed to open access.

By publishing the Human Genome Project’s first paper, we worked with a publicly funded initiative that was committed to data sharing. But the journal acknowledged there would be challenges to maintaining the free, open flow of information, and that the research community might need to make compromises to these principles, for example when the data came from private companies. Indeed, in 2001, colleagues at Science negotiated publishing the draft genome generated by Celera Corporation in Rockville, Maryland. The research paper was immediately free to access, but there were some restrictions on access to the full data.

NIH and UCSF ENCODE researchers are on Reddit right now!

Check out Science AMA Series: We’re Drs. Michael Keefer and James Kobie, infectious .... (Thanks to Paul Nelson for alerting me to the discussion.)

Here's part of the introduction ...

Yesterday NIH announced its latest round of ENCODE funding, which includes support for five new collaborative centers focused on using cutting edge techniques to characterize the candidate functional elements in healthy and diseased human cells. For example, when and where does an element function, and what exactly does it do.

UCSF is host to two of these five new centers, where researchers are using CRISPR gene editing, embryonic stem cells, and other new tools that let us rapidly screen hundreds of thousands of genome sequences in many different cell types at a time to learn which sequences are biologically relevant — and in what contexts they matter.

Today’s AMA brings together the leaders of NIH’s ENCODE project and the leaders of UCSF’s partner research centers.

Your hosts today are:

Nadav Ahituv, UCSF professor in the department of bioengineering and therapeutic sciences. Interested in gene regulation and how its alteration leads to morphological differences between organisms and human disease. Loves science and juggling.
Elise Feingold: Lead Program Director, Functional Genomics Program, NHGRI. I’ve been part of the ENCODE Project Management team since its start in 2003. I came up with the project’s name, ENCODE!
Dan Gilchrist, Program Director, Computational Genomics and Data Science, NHGRI. I joined the ENCODE Project Management team in 2014. Interests include mechanisms of gene regulation, using informatics to address biological questions, surf fishing.
Mike Pazin, Program Director, Functional Genomics Program, NHGRI. I’ve been part of the ENCODE Project Management team since 2011. My background is in chromatin structure and gene regulation. I love science, learning about how things work, and playing music.
Yin Shen: Assistant Professor in Neurology and Institute for Human Genetics, UCSF. I am interested in how genetics and epigenetics contribute to human health and diseases, especial for the human brain and complex neurological diseases. If I am not doing science, I like experimenting in the kitchen.

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Was ENCODE Worth It?

Michael Eisen is in a good position to ask whether the $200,000,000 spent on the ENCODE project was worth the money: Blinded by Big Science: The lesson I learned from ENCODE is that projects like ENCODE are not a good idea.

Here's part of what he says.

As I and many others have discussed, the media campaign around the recent ENCODE publications was, at best, unseemly. The empty and often misleading press releases and quotes from scientists were clearly masking the fact that, despite publishing 30 papers, they actually had very little of grand import to say, today, about what they found. The most pensive of them realized this, and went out of their way to emphasize that other people were already using the data, and that the true test was how much the data would be used over the coming years.

I'm not in a good position to judge whether the American investment was worthwhile but I can echo Michael Eisen's point about the importance of the data. We didn't learn anything new about the functional organization of the human genome. The conclusion that was most often attributed to the ENCODE result; namely, that almost all the genome is functional, is wrong.

I think this is a case where the misleading publicity campaign, aided and abetted by Nature and science journalists, has backfired. It has caused many people like Michael Eisen to question the value of ENCODE. Such questions might not have arisen if the consortium hadn't tried to put an improper spin on their results.

I feel sorry for the hundreds of graduate students, postdocs, and PI's involved in the consortium. The importance of their work, and the years of effort it took, are being overshadowed by the decision of a few leaders to make claims about it that don't hold up to scientific scrutiny.

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ENCODE & Junk and Why We Call Them IDiots

The Intelligent Design Creationists have been following the debate over the ENCODE results. For them this is a serious issue since they are committed to the idea that well-designed genomes should not be full of junk. You'd think that the IDiots would make an attempt to learn the real scientific issues at stake.

Let's see how andyjones does on Uncommon Descent: Function, the evolution-free gospel of ENCODE. He says,

Apparently, ENCODE are to be criticised for using an ‘evolution-free’ definition of function. Yep, you heard that right. You thought that function was function was function, but oh no, you must use a evolution-y definition or you will not get the ‘correct’ evolution-y answer. It seems awfully like you need to presuppose Darwinism or you will not find Darwinism. Can that be right?

The excuse for this is some interesting Darwinian philosophy (or do I mean sophistry? – make up your mind below): the authors believe that function means nothing (is purely subjective) unless it is selected for. For example, the heart causes the pericardium (the membrane around the heart) to not collapse by filling space, so we could call that a function, but it is selected for pumping blood.

....

Amongst other things the ENCODE authors are lambasted for not distinguishing between ‘Junk DNA’ and ‘Garbage DNA’. No seriously, ‘junk’ now means stuff that is functional, but not used very often, but could be used, like stuff in your attic is ‘junk’. It is different from ‘garbage’, which is the stuff that you would put straight in the bin. ‘junk’ is now a rather misleading word for ‘functional’. So our genome is full of ‘junk’ that is useful and functional, but to a Darwinian it does not count until it starts getting used so that natural selection can get the credit. How convenient! The possibility of design is sidestepped by careful choice of language. Welcome to 1984! A better word might be ‘archived’ rather than ‘junk’.

...

I, and many of us, hold to an ID worldview firstly and most securely because of what we know about prebiotic chemistry and thus the origin of the first life form. Based on that, because I know there has been a designer involved, I think probably a lot of ‘junk’ will turn out to be ‘brought down from the attic’ at various stages of an organisms life, especially in the developing stages. Time will tell.

Scientific means finding out what is actually there. ENCODE are to be praised for doing that. Darwinism has always been about telling creation myths from the point of view of naturalism (roughly, physics only), and shoehorning every fact into the story. ENCODE are now receiving scorn because they did not wait for the Darwinian imprimatur. Intelligent Design people and creationists (in fact everyone who is not a Darwinist) should take courage from this, jump in and start driving forward ordinary mainstream science, but just make sure they sidestep the attempts to sign them up to that cult.

Does anyone still wonder why I refer to Intelligent Design Creationists as IDiots?

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Junk DNA is so last century!

My copy of John Parrington's new book, The Deeper Genome: Why there is more to the human genome than meets the eye, is due to arrive in about three weeks. However, we already have a number of clues about what's in the book [see How the genome lost its junk according to John Parrington]. The excerpt on Amazon [How the genome lost its junk] tells us that Parrington is aware of the controversy surrounding the ENCODE project but comes down on the side of ENCODE.

That view is shared by science writer Claire Ainsworth who wrote a review in New Scientist: Its' so last century.¹ Ainsworth is a freelance science writer with a Ph.D. in developmental genetics from Oxford (Oxford, UK). She is co-founder of SciConnect, a company that teaches science communication skills to scientists.

Here's what she says in her review ....

John Parrington is an associate professor in molecular and cellular pharmacology at the University of Oxford. In The Deeper Genome, he provides an elegant, accessible account of the profound and unexpected complexities of the human genome, and shows how many ideas developed in the 20th century are being overturned.

Take DNA. It's no simple linear code, but an intricately wound, 3D structure that coils and uncoils as its genes are read and spliced in myriad ways. Forget genes as discrete, protein-coding "beads on a string": only a tiny fraction of the genome codes for proteins, and anyway, no one knows exactly what a gene is any more.

A key driver of this new view is ENCODE, the Encyclopedia of DNA Elements, which is an ambitious international project to identify the functional parts of the human genome. In 2012, it revealed not only that the protein-coding elements of DNA can overlap, but that the 98 per cent of the genome that used to be labelled inactive "junk" is nothing of the sort. Some of it regulates gene activity, some churns out an array of different kinds of RNA molecules (RNAs for short), some tiny, some large, many of whose functions are hotly debated. Parrington quotes ENCODE scientist Ewan Birney as saying at the time, "It's a jungle in there. It's full of things doing stuff." And that is one of the most apt genome metaphors I've ever read.

People, including science writers, can have different opinions about the validity of the ENCODE results and whether most of our genome is junk. They can also have different opinions about whether many of the ideas developed in the 20th century are still valid. However, I think it's only fair to at least acknowledge that others may have different opinions.

Ainsworth must be aware of the controversy over ENCODE's claim that most of our genome has a function. She could have pointed out that Parrington supports the function side but many prominent scientists support the junk DNA side. She could have noted that there have been several scientific papers published since 2012 that defend the concept of junk DNA—and defend it very well.

A good science journalist can express an opinion on a scientific controversy but good science journalists are obliged to point out to their readers that this is just an opinion and there are many expert scientists who disagree.

The readers of this New Scientist book review will think that ENCODE was the last word on the debate and that's not good science reporting.

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1. The title of the online version is "DNA is life's blueprint? No, there's far more to it than that."

The apophenia of ENCODE or Pangloss looks at the human genome

This is a paper in French by Casane et al. (2015). Most of you won't be able to read it but the English abstract gives you the gist of the argument. I had to look up "apophenia": "Apophenia has come to imply a universal human tendency to seek patterns in random information, such as gambling."

In September 2012, a batch of more than 30 articles presenting the results of the ENCODE (Encyclopaedia of DNA Elements) project was released. Many of these articles appeared in Nature and Science, the two most prestigious interdisciplinary scientific journals. Since that time, hundreds of other articles dedicated to the further analyses of the Encode data have been published. The time of hundreds of scientists and hundreds of millions of dollars were not invested in vain since this project had led to an apparent paradigm shift: contrary to the classical view, 80% of the human genome is not junk DNA, but is functional. This hypothesis has been criticized by evolutionary biologists, sometimes eagerly, and detailed refutations have been published in specialized journals with impact factors far below those that published the main contribution of the Encode project to our understanding of genome architecture. In 2014, the Encode consortium released a new batch of articles that neither suggested that 80% of the genome is functional nor commented on the disappearance of their 2012 scientific breakthrough. Unfortunately, by that time many biologists had accepted the idea that 80% of the genome is functional, or at least, that this idea is a valid alternative to the long held evolutionary genetic view that it is not. In order to understand the dynamics of the genome, it is necessary to re-examine the basics of evolutionary genetics because, not only are they well established, they also will allow us to avoid the pitfall of a panglossian interpretation of Encode. Actually, the architecture of the genome and its dynamics are the product of trade-offs between various evolutionary forces, and many structural features are not related to functional properties. In other words, evolution does not produce the best of all worlds, not even the best of all possible worlds, but only one possible world.

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Casane, D., Fumey, J., et Laurenti, P. (2015) L’apophénie d’ENCODE ou Pangloss examine le génome humain. Med. Sci. (Paris) 31: 680-686. [doi: 10.1051/medsci/20153106023]

The quality of the modern scientific literature leaves much to be desired

Lately I've been reading a lot of papers on genomes and I've discovered some really exceptional papers that discuss the existing scientific literature and put their studies in proper context. Unfortunately, these are the exceptions, not the rule.

I've discovered many more authors who seem to be ignorant of the scientific literature and far too willing to rely of the opinions of others instead of investigating for themselves. Many of these authors seem to be completely unaware of controversy and debate in the fields they are writing about. They act, and write, as if there was only one point of view worth considering, theirs.

How does this happen? It seems to me that it can only happen if they find themselves in an environment where skepticism and critical thinking are suppressed. Otherwise, how do you explain the way they write their papers? Are there no colleagues, post-docs, or graduate students who looked at the manuscript and pointed out the problems? Are there no referees who raised questions?

When philosophers talk about genomes

Postgenomics is a compendium of twelve scholarly articles by philosophers and sociologists who write about the implication of the human genome sequence and subsequent work on interpreting the results. The volume is edited by Sarah Richardson, a professor in Social Sciences (History of Science) at Harvard University (Boston, Massachusetts, USA), and by Hallam Stevens, a professor of History at Nanyang Technology University in Singapore (Singapore).


The first essay is by Stevens and Richardson and it outlines the goal of the book.

Junk DNA in New Scientist

I just got my copy of the July 14th issue of New Scientist so I can comment on the article Why 'junk DNA' may be useful after all by Aria Pearson. RPM at evolvgen thinks it's pretty good [Junk on Junk] and so does Ryan Gregory at Genomicron [New Scientist gets it right]. I agree. It's one of the best articles on the subject that I've seen in a long time.

First off, Aria Pearson does not make the common mistake of assuming that junk DNA is equivalent to non-coding DNA. The article makes this very clear by pointing out that we've known about regulatory sequences since the 1970's. The main point of the article is to discuss recent results that reveal new functions for some of the previously unidentified non-coding DNA that was classified as junk.

One such result is that reported Pennacchio et al. (2006) in Nature last year. They analyzed sequences in the human genome that showed a high degree of identity to sequences in the pufferfish genome. The idea is that these presumably conserved sequences must have a function. Pennacchio et al. (2006) tested them to see it they would help regulate gene expression and they found that 45% of the ones they tested functioned as enhancers. In other words, they stimulated the expression of adjacent genes in a tissue specific manner. The authors estimate that about half of the "conserved" elements play a role in regulating gene expression.

There are a total of 3,124 conserved elements and their average length is 1,270 bp. This accounts for 3.9 × 10⁶ bp out of a total genome size of 3.2 × 10⁹ bp or about 0.1% of the genome. The New Scientist article acknowledges, correctly, that more than 95% of the genome could still be junk.

Is this all junk DNA? Unlike most other science journalists, Pearson addresses this question with a certain amount of skepticism and she makes an effort to quote conflicting opinions. For example, Pearson mentions experiments claiming that ~90% of the genome is transcribed. Rather than just repeating the hype of the researchers making this claim, Pearson quotes skeptics who argue that this RNA might be just "noise."

Most articles on junk DNA eventually get around to mentioning John Mattick who has been very vocal about his claim that the Central Dogma has been overturned and most of the genome consists of genes that encode regulatory RNAs (Mattick, 2004; Mattick, 2007). This article quotes a skeptic to provide some sense of balance and demonstrate that the scientific community is not overly supportive of Mattick.

Others are less convinced. Ewan Birney of the European Bioinformatics Institute in Cambridge, UK, has bet Mattick that of the processed RNAs yet to be assigned a function - representing 14 per cent of the entire genome - less than 20 per cent will turn out to be useful. "I'll get a case of vintage champagne if I win," Birney says.

Under the subtitle "Mostly Useless," Pearson correctly summarizes the scientific consensus. (I wish she had used this as the title of the article. The actual title is somewhat misleading. Editors?)

Whatever the answer turns out to be, no one is saying that most of our genome is vital after all. "You could chuck three-quarters of it," Birney speculates. "If you put a gun to my head, I'd say 10 per cent has a function, maybe," says Lunter. "It's very unlikely to be higher than 50 per cent."

Most researchers agree that 50 per cent is the top limit because half of our genome consists of endless copies of parasitic DNA or "transposons", which do nothing except copy and paste themselves all over the genome until they are inactivated by random mutations. A handful are still active in our genome and can cause diseases such as breast cancer if they land in or near vital genes.

The ENCODE project made a big splash in the blogosphere last month (ENCODE Project Consortium, 2007). This study purported to show that much of the human genome was transcribed, leading to the suggestion that most of what we think is junk actually has some function. Aria Pearson interviewed Ewan Birney (see above) who is involved in the ENCODE project.

The real surprise is that ENCODE has identified many non-coding sequences in humans that seem to have a function, yet are not conserved in rats and mice. There seem to be just as many of these non-conserved functional sequences as there are conserved ones. One explanation is that these are the crucial sequences that make humans different from mice. However, Birney thinks this is likely to be true of only a tiny proportion of these non-conserved yet functional sequences. Instead, he thinks most are neutral. "They have appeared by chance and neither hinder nor help the organism."

Put another way, just because a certain piece of DNA can do something doesn't mean we really need it to do whatever it does. Such DNA may be very like computer bloatware: functional in one sense yet useless as far as users are concerned.

This is a perspective you don't often see in popular articles about junk DNA and Pearson is to be commended for taking the time and effort to find the right scientific perspective.

The article concludes by reporting the efforts to delete large amounts of mouse DNA in order to test whether they are junk or not. The results show that much of the conserved bits of DNA can be removed without any harmful effects. Some researchers urge caution by pointing out that very small effects may not be observed in laboratory mice but may be important for evolution in the long term.

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ENCODE Project Consortium (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816. [PubMed Abstract]

Mattick, J.S. (2004) The hidden genetic program of complex organisms. Sci. Am. 291:60-7.

Mattick, J.S. (2007) A new paradigm for developmental biology. J. Exp. Biol. 210:1526-47. [PubMed Abstract].

Pennacchio, L.A., Ahituv, N., Moses, A.M., Prabhakar, S., Nobrega, M.A., Shoukry, M., Minovitsky, S., Dubchak, I., Holt, A., Lewis, K.D., Plajzer-Frick, I., Akiyama, J., De Val, S., Afzal, V., Black, B.L., Couronne, O., Eisen, M.B., Visel, A., Rubin, E.M. (2006) In vivo enhancer analysis of human conserved non-coding sequences. Nature 444(7118):499-502.

ENCODE, Junk DNA, and Intelligent Design Creationism

andyjones has replied to my earlier posting on ENCODE and junk DNA. You can read his response at: (More) Function, the evolution-free gospel of ENCODE. Here's part of what he says ...

Larry Moran has sort-of replied to my previous blogpost but disappoints with only one substantive point. And even that one point is wrong: ID is not committed to the idea that individual genomes be well-designed; that is just an expectation some of us derive based on belief in a designer which is established on other evidence. ID would still be true if only globular proteins were designed (lookup Axe), or even if only the flagellum was designed (lookup Behe), or even if only the first life form was designed (lookup Meyer – and please read their actual work, not cheap reviews, because reviewers often dont pick up on the salient points – more below). I just say this lest readers get the impression that this is ID’s strongest point, or in any sense a weak point. It is neither.

It's true that there are some IDiots who are distancing themselves from a commitment to junk DNA. There are probably some who claim that they could live with the fact that 90% of our DNA is junk.

But let's not forget that Jonathan Wells is a prominent IDiot and he wrote a book on The Myth of Junk DNA. It sounded very much like Intelligent Design Creationism is staking its reputation on finding function for most of our genome.

James Shapiro Never Learns

One of the remarkable things about kooks is that they are incredibly resistant to learning from their mistakes. James Shapiro gives us a fine example in one of his latest articles on The Huffington Post where he tries to convince us that the old definition of "gene" has outlived its usefulness. According to Shapiro, "DNA and molecular genetics have brought us to a fundamentally new conceptual understanding of genomes, how they are organized and how they function."

Really? While we all can agree that there's no definition of "gene" that doesn't have exceptions, we can surely agree that some definitions work pretty well. I've argued that defining a gene as, "a DNA sequence that is transcribed to produce a functional product" works well in most cases [What Is a Gene?].

Let's see how James Shapiro handles this problem.¹ He says,

The identification of DNA as the key molecule of heredity and Crick's Central Dogma of Molecule Biology [Crick 1970] initially seemed to confirm Beadle and Tatum's "one gene -- one enzyme" hypothesis.

I've already explained that Shapiro doesn't understand the Central Dogma of Molecular Biology even though he quotes the Francis Crick papers that explain it correctly [Revisiting the Central Dogma in the 21st Century]. I also made this point in my review of his book: Evolution: A View from the 21st Century.