Comments on Birney’s blog.

Ewan Birney, lead coordinator of ENCODE, has a blog. I thought I might re-post a couple of comments from there on here.

First, a weird criticism of me from someone calling himself “TheMayan”. He has written similar things in the comments on my blog. (Don’t you just love the confidence that a pseudonym provides?)

You have T. Ryan Gregory complaining that function had already been known for years, yet on the other hand, complaining about the fact that a large amount of bio chemical function has been found. Which is it Gregory? Make up your mind! Of course what he refuses to admit, is that in the earlier years, the data that did indeed give hint to function, was largely ignored by the status quo, and now all those years of preaching the useless junk DNA paradigme to students and to the general public has now come back to bite them in the ass. Not to mention those all those sweet talking points given to ID theorist and creationist. No, we just couldn’t have that! (Sarcasm emphasized)

As for Larry Moran challenging the findings of ENCODE. My question is, why cant he do this in peer review? If the counter evidence is there, as he insist it is, then he wouldn’t even need funding. He could simply produce the data that already exist, but like Gregory, he chooses instead, to publicly ridicule and or marginalize the work of other very hard working researchers who have dedicated their precious time and effort into this project.

Again, it is easy to criticize from your a blog where your minions can shower you with praise and un-critical adulation. Do it the right way. Take it to the stage.

Hmmmmpf. First of all, I don’t have minions and my blog is definitely not a source of uncritical adulation, and neither is Larry‘s. We both allow open comments, including from the likes of TheMayan. Second, I do publish criticisms of ideas that I think are inaccurate in the primary literature. A few examples:

Linquist, S., B. Saylor, K. Cottenie, T.A. Elliott, S. Kremer, and T.R. Gregory (2012). Distinguishing ecological from evolutionary approaches to transposable elements. Biological Reviews, in press.

Gregory, T.R. and J.D.S. Witt (2008). Population size and genome size in fishes: a closer look. Genome 51: 309-313.

Gregory, T.R. (2004). Insertion-deletion biases and the evolution of genome size. Gene 324: 15-34.

Gregory, T.R. (2004). Genome size is not correlated positively with longevity in fishes (or homeotherms). Experimental Gerontology 39: 859-860.

Gregory, T.R. (2003). Is small indel bias a determinant of genome size? Trends in Genetics 19: 485-488.

My blog is an additional venue for discussing ideas that are of interest to a broader audience, in a more accessible and rapid format. It does not take the place of my publishing peer-reviewed critiques where warranted.

Anyway, here is the response that I posted on Birney’s blog:

It’s not complicated, Themayan. My complaint has three parts (and this isn’t unique to ENCODE, it’s so common as to be cliche in both the media and the primary literature).

First, there was never a time when non-coding DNA was *all* dismissed as “useless junk” such that functions were not considered. Quite the opposite — functions were seriously considered for every new type of non-coding DNA when discovered. The early authors of the “junk DNA” concept explicitly mentioned possible functions for *some* non-coding DNA. Comings (1972) suggested 20% of the genome is actively used, for example.

Second, the concept of non-functional, non-coding DNA was not based on ignorance or giving up and just calling it “junk”. There were (and still are) positive arguments for expecting much of the genome to be of little or no relevance to fitness. Mutational loads, variability in genome size, neutral evolution at the sequence level, 2/3 of the genome being transposable elements, etc. Several of these arguments have been around since the 1970s and they remain valid today.

Third, there is no evidence that a majority of the human genome is “functional” in any meaningful sense of that word. Of course some non-coding DNA is functional (regulatory regions, centromeres and telomeres, ribosomal RNA, etc.), but no one ever said otherwise. There are more examples coming up all the time, which is very interesting. But the total still hasn’t even approached Comings’s (1972) original figure of 20%. And even if some people are willing to interpret the current evidence as indicating that most DNA in the human genome will turn out to be functional, they still have to explain why a pufferfish does fine with only 1/10 as much whereas even the smallest salamander genome is 5x larger. This suggests that, even if 100% of the human genome is functional, a lot of eukaryotic DNA out there is not. That is, that the notion of non-functional, non-coding DNA remains valid. Claiming that humans are complex and so need more DNA is an expectation that was refuted in the 1950s. And, in any case, the human exceptionalism required to maintain the view that 100% is functional in people but the amount of non-coding DNA is irrelevant in pufferfishes and salamanders is biologically nonsensical.

There is nothing contradictory about these three arguments.

UPDATE: TheMayan was back, and here is my reply to his latest claims:

TheMayan:

“…the possibility that TEs could influence genetic polymorphism, and therefore genetic diversity, was, for the most part, ignored.”

Surely you jest.

http://www.nobelprize.org/nobel_prizes/medicine/laureates/1983/

It may very well be that your undergraduate instructors told you that junk DNA was all useless. It does not follow that researchers working on non-coding DNA dismissed the idea of function. That is what I have tried to show — they published ideas on potential function all the time in the primary literature throughout the 1970s and 1980s. Every new type of non-coding DNA that was discovered (satellite DNA, LINEs, SINEs, ERVs, introns, and pseudogenes) had functions considered from the outset.

It also does not follow from whaty you heard in class or what you saw in Scientific American that the authors of the original junk DNA papers argued that all non-coding DNA is useless. Read Comings (1972), which is the first detailed treatment of the topic. Moreover, both the junk DNA and selfish DNA papers were met with strong resistance — the prevailing view was that most genomic DNA must have a function or else it would have been deleted.

Ohno’s version of “junk DNA” referred to pseudogenes, which is the context for the line you quoted. He did acknowledge non-sequence specific functions such as spacing among genes.

Of course, all of this is secondary to the fact that the ENCODE results do not, in fact, suggest anything like 80% “functional” non-coding DNA in the human genome under any biologically meaningful definition.

Finally, for an “oh, snap!” kind of comment, it’s hard to beat the one posted by Diogenes:

Birney: “For me, the driving concern was to avoid over-hyping the medical applications…”

Really? You mean like when you helped Nature produce a video cartoon in which ENCODE is presented as a mega-robot that destroys cancer and heart disease by punching it very hard?

Is that what you meant by avoiding over-hyping of medical applications? What, then, WOULD be hype by your definition? Immortality? Free nose jobs for ugly children? The ability to fly? What?

Birney: “With hindsight, we could have used different terminology to convey the concepts…”

True, you could have used accurate terminology.

Birney: “I do think we got our point to the general public: that there is a staggering amount of activity in the genome…”

No, no. You told the general public that there was 80% FUNCTION in the genome, FUNCTION not activity, and you told Ed Yong at Discover that would go to 100%. And almost all of the media interpreted function to mean “necessary”, “needed”, “essential”. Was that accurate?

NPR reported John Stam as saying:

NPR: “Most of the human genome is out there mainly to control the genes,” said John Stamatoyannopoulis, a geneticist at the University of Washington School of Medicine, who also participated in the project.

Was John Stam telling the truth or lying, Ewan?

This is from the Independent:

The Independent: “Scientists have once and for all swept away any notion of “junk DNA” by showing that that the vast majority of the human genome does after all have a vital function by regulating the genes that build and maintain the body.”

Does the vast majority of the human genome have a vital function by regulating the genes, Ewan?

This is from the New York Times:

NY Times: “As scientists delved into the “junk” — parts of the DNA that are not actual genes containing instructions for proteins — they discovered a complex system that controls genes. At least 80 percent of this DNA is active and needed.

Is 80% of human DNA active and needed, Ewan?

This is from the Washington Post:

Wash Post: “Indeed, the vast majority of human DNA seems to be involved in maintaining individuals’ well being — a view radically at odds with what biologists have thought for the past three decades”

Is the vast majority of human DNA involved in maintaining individuals’ well being, Ewan?

This is from USA Today:

USA Today: “International research teams have junked the notion of “junk” DNA, reporting that at least 80% of the human genetic blueprint contains gene switches, once thought useless, that control the genes that make us healthy or sick.”

Is 80% of human DNA gene “switches” that control genes, Ewan?

Birney: “ENCODE also had the chance of making our results comprehensible to the general public…”

Ewan, did you succeed or fail?


4 comments to Comments on Birney’s blog.

  • TheMayan’s criticism that you and Larry don’t put your complaints in peer-reviewed publications misses the point that the problem is not so much with the actual ENCODE publications. The problem is with the statements to the media and commentaries written about ENCODE. There is no need for a peer-reviewed rebuttal to the actual ENCODE papers.

    The papers themselves are pretty much straightforward reporting of results of the various [X]-seq assays, without much controversial interpretation. Is it really surprising or controversial or radical that 60% of the genome is represented in a transcript in some cell type? No.

      (Quote)

  • Well, the “we can assign biochemical function to 80% of the genome” is very, very misleadingly worded, but I don’t have a problem with the analyses themselves.

      (Quote)

  • David Marjanović

    <i>As for Larry Moran challenging the findings of ENCODE. My question is, why cant he do this in peer review?</i>
     
    …Whut? How fast does TheMayan believe the publication process works?
     
    Fairly common example: I had a manuscript accepted for publication several months ago. I’ll get the page proofs in January, and publication is scheduled for March, around a year after acceptance.

      (Quote)

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