Thursday, September 06, 2012

You Just Knew This Was Coming, Didn't You?

Jonathan McLatchie must have hardly been able to contain himself when he wrote: Latest ENCODE Research Validates ID Predictions On Non-Coding Repertoire.
Readers will likely recall the ENCODE project, published in a series of papers in 2007, in which (among other interesting findings) it was discovered that, even though the vast majority of our DNA does not code for proteins, the human genome is nonetheless pervasively transcribed into mRNA. The science media and blogosphere is now abuzz with the latest published research from the ENCODE project, the most recent blow to the “junk DNA” paradigm. Since the majority of the genome being non-functional (as has been claimed by many, including notably Larry Moran, P.Z. Myers, Nick Matzke, Jerry Coyne, Kenneth Miller and Richard Dawkins) would be surprising given the hypothesis of design, ID proponents have long predicted that function will be identified for much of our DNA that was once considered to be useless. In a spectacular vindication of this hypothesis, six papers have been released in Nature, in addition to a further 24 papers in Genome Research and Genome Biology, plus six review articles in The Journal of Biological Chemistry.

...

This new research places a dagger through the heart of the junk DNA paradigm, and should give adherents to this out-dated assumption yet further cause for caution before they write off DNA, for which function has yet to be identified, as “junk".
Not much I can say right now. I'm up to my ears trying to convince sane people that the ENCODE papers are wrong. The IDiots are just going to have to wait.


39 comments :

  1. The Half Crazed Cleaning Lady from Sector &%@Thursday, September 06, 2012 5:16:00 PM

    "I'm up to my ears trying to convince sane people that the ENCODE papers are wrong."

    Spoken like a true science denier.

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    1. Spoken like a true ignoramus who doesn't understand the role of skepticism in science.

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  2. Wow, what a pathetic post. Despite being "up to your ears" trying to persuade people, you've nothing to say here other than to use abusive words like "IDiots" and infer that those who disagree are insane. This only gives away your own bias and adolescent agenda.

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    1. I agree. This blog is an embarrassment to science.

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    2. I see the concern trolls are out in force...

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  3. The ENCODE papers are not wrong, they misinterpreted their own data.

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    1. Just because a part of the genome is transcribed, binds to a transcription factor or has some activity associated with it, it does not follow that this genomic loci is not junk.

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    2. This is correct, but they make other assumptions too, e.g. DNAse hypersensitivity or transcription factor binding demonstrate function. These standards would lead us to infer function in randomly generated DNA sequences.

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    3. Alex is quibblimg.

      The main paper says that 80% of the genome has a function. That's just wrong.

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    4. The main paper says that 80% of the genome has a function. That's just wrong.

      The main paper mentioned biochemical function. If a segment of DNA that can serve as a substrate for RNA polymerase in the cell, then it has a clear biochemical function in the cell.

      Whether or not the product(s) of the particular reaction affect anything, well, that's a whole different semantic quibble.

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    5. It's not me who's quibbling about the meaning of the word "function." Up until a few days ago everyone had a pretty good understanding of what the word meant. Now we know that there are a handful of people who want tne word to mean something else.

      Those people have managed to get a lot of publicity by deliberately using the word in a non-standard way. They've fooled a lot of people who thought they were talkig about real function. That's shameful. I'm pretty sure that they knew exactly what they were doing.

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  4. How is the non-existence of junk even a proper prediction of ID? I can see that it's a prediction of YEC (no time to accumulate much junk), but even an OEC would need to postulate some sort of divine intervention to keep junk from entering the genome, and that's a hypothesis entirely separate from ID itself. I can see "God doesn't create junk", but how do you turn that into "God periodically cleans house"?

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  5. //How is the non-existence of junk even a proper prediction of ID? I can see that it's a prediction of YEC (no time to accumulate much junk//

    Good question, Dembski put it this way:

    “..design is not a science stopper..Indeed, design can foster inquiry where traditional evolutionary approaches obstruct it. Consider the term “junk”. Implicit in this term is the view that because the genome of an organism has been cobbled together through a long, undirected evolutionary process, the genome is a patchwork of which only limited portions are essential to the organism. Thus on an evolutionary view we expect a lot of useless DNA. If, on the other hand, organisms are designed, we expect DNA, as much as possible, to exhibit function.And indeed, the most recent findings suggest that designating DNA as “junk” merely cloaks our current lack of knowledge about function..Design encourages scientists to look for function where evolution discourages it."

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    1. So Dembski, who as usual doesn't actually state his position, is either a YEC or an OEC with some kind of auxiliary hypothesis of divine genome maintenance.

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    2. He is certainly making a "good design" argument. Normally ID types denounce bad-design arguments but then they turn around and make good-design arguments when it comes to junk DNA.

      This also makes clear where in ID arguments we find the prediction that there is no junk DNA: in the theology part.

      Jonathan McLatchie needs to be asked: so where exactly in ID theory does that prediction come from? If he is frank about it he will have to admit that it comes from religious doctrine.

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    3. What seems to excite ID commenters most is the widespread, mistaken belief that junk has been used to buttress evolutionary theory. I think it comes from this: Common Descent data pointing to a link in nonfunctional DNA is less readily wafted away by some 'common design' argument. But since nonfunctional is also likely to equate to nonconserved, these would be the signals that degrade most rapidly, so this is a fairly shallow probe, linking species that even ID-ers might accept could arise 'naturally'. Junk yes/no is hardly central to evolutionary theory.

      What is amusing is the uncritical eagerness with which ID latches on to this work - which hardly came out of ID 'encouragement' of scientists - when the vast body of other work produced by the mainstream is either chewed to bits or ignored by McLatchie et al.

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    4. If I remember correctly, this whole junk DNA "controversy" stated in the 1990s because the IDers had been long taunted about the fact that ID didn't make any predictions. Some (YEC, again IIRC) who had been employed in some postion (editor?) by Scientific Amwerican wrote something about how junk DNA would be disproven. When the first doubt was raised in the scientific literature about the amount of junk DNA, the IDers leapt on it as a "prediction" of ID, ignoring the fact that "Darwinism" didn't actually predict junk DNA (though it was pointed out that it was compatible with evolution and some people argued -- correctly or not -- that it was as incompatible with ID for the same reason as the panda's thumb). It is, no doubt, an interesting scientific question but the metaproblem is the ammunition it has given to the creationists.

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    5. Actually, I think that this "prediction" by ID/creationists is really a post-diction - they saw the hype of the Matticks of the world, saw that most scientists were not buying it, and decided to run with it.

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  6. Translation: the prediction is not a prediction and does not follow from ID. Rather it follows from Dembski's alleged ability to divine the mind of God, which is metaphysics at best, or plain appeal to authority at worst. In no case is it science nor a scientific prediction.

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  7. I can't get interested in who wins a ball game and who doesn't. Never could.

    Just because a part of the genome is transcribed, binds to a transcription factor or has some activity associated with it, it does not follow that this genomic loci is not junk. aplazzo

    Not that I care, because this seems to be a pissing match instead of something important, but how do you know that something that seems to be "junk" doesn't just have a function that you haven't understood yet? I'd be asking your foes how they know that what appears to be function but the function of which isn't defined is actually a function.

    And if it turns out that a lot of that "junk" is more than junk, is it going to force you to change your mind about the existence of God? I don't get how that would make a difference. Why can't God created "junk"? Keeping in mind that "junk" is something people define. Apparently not with 100% precision or unanimity, at that.

    Seems like a bad position to stake your faith on. In both cases.

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  8. I also don't see how this helps ID, but then again, ID is non-testable. I still hold that biologists need to abandon the term "junk" - it is too loaded a term and implies that the particular bit of DNA under discussion is known to be non-functional, by which I mean code that has no effect on phenotype. As has been pointed out, a lot of the non-coding DNA that was initially assumed to be "junk" has been revealed to have a function (promoters, etc.) and it was hubris then to suggest that all non translated code was junk, and it is hubris now to suggest the same just because we don't know what if anything some of the code does. However, the issue under discussion here is that it is pretty clear that some portion of the genome does not appear to affect phenotype in any measurable way. As with anything it is impossible to prove a negative, but there is a good amount of evidence that some is what I would call (or would have prior to yesterday, at least) "non-functional" DNA like retrotransposons (what would ENCODE have us call transposons?). So let's abandon the term "junk" given its fraught history, which might allow us the intellectual space to call upon the ENCODE scientists to explain to the science journalists the difference between functional regulatory non-coding DNA and repeated sequences, etc.

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    1. I prefer the term "scar DNA" because transposons etc. are analogous to scars from past infections.

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  9. It's people like this that make me glad some science goes past the diplomatic process. You have more people wanting to hear the sound of their voice, than you do people who want to see things move forward. And talking down to your peers, is not moving FWD.

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  10. I'm a laymen trying to understand Laurence's viewpoint on this.

    Basically, the discrepancy is in the definition of "functional".

    ENCODE says 80% of DNA is functional and leaves it at that.

    Laurence says functional should be better defined to really be understood as "meaningful DNA" and that only 10% is meaningful to human development (oversimplified - making a liver, setting hair color, etc). Therefore, anything not meaningful is "junk" and 90% of our DNA is still "junk". It maybe doing something as Encode shows, but it doesn't really matter.

    Before 2007, the debate was that most of our DNA wasn't doing anything, it was just there. Then around 2007 it was determined most DNA is indeed doing something, but it's irrelevant to humans. Now, with ENCODE, lack of clarity has made it sound like 80% is truly relevant but Laurence disagrees.

    Sorry if my post shows up twice, I posted and nothing happened so I had to retype it.

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    1. You've got it exactly right. The junk/non-junk distinction has always been about whether DNA was important for the development and maintenance of an adult and healthy organism.

      The ENCODE project has merely succeeded in showing that large portions of DNA has some kind of activity. But it could still have absolutely no effect on the organism. They have NOT managed to show that any of the new DNA they now say has function, is in any way important to the human organism.

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    2. Bjørn Østmand has a nice little post on his blog, Pleiotropy too:
      http://pleiotropy.fieldofscience.com/2012/09/encode-what-defines-genomic-function.html

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  11. Define "doing something". I think Larry's position is that binding a protein is "doing something" only if there is some effect on phenotype, or visibility to selection, or if it's something that completely random sequences wouldn't do to the same degree. Sounds like a reasonable position to me.

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  12. Regarding the suggestion that "even an OEC would need to postulate some sort of divine intervention to keep junk from entering the genome"

    I think you're neglecting a rather important process called "natural selection". If you blast a couple of cosmic rays at a bacterium an mutate to junk part of its genome, a genome that is already tightly packed with code for useful proteins, odds are high that you'll end up eradicating something associated with respiration, food collection, reproduction, or some other critical life support system. Even if you don't, you'll knock out of operation their photosensitive spot or another useful add on.
    As a result, that bacterium is very likely to die. Even if it doesn't die immediately, its descendents aren't going to compete very well with all the other bacteria in the area.
    Therefore the accumulation of "junk" is quickly halted.

    This is actually part of the reason that very low levels of Junk is part of the ID hypothesis and not part of the naturalistic evolutionary one. It would be very hard to evolve a new feature if all your otherwise beneficial mutations break the features that you've already got, and are thus strongly selected against. It would be much easier to evolve a new feature if most of the genome is junk. By way of an old and famous analogy, you may be able to evolve "Methinks it is like a weasel" if your starting text is "XIOJOAJOBVHIBOIQWOIJOGIHBOIHWOIBOWBHEOHBOWIHBOUFOSJFOHWOBHWOIFUWE", or even "By the mass, and ’t is like a camel, indeed.WOIBOWBHEOHBOWIHBOUFOSJFOHWOBHWOIFUW" However if your starting text is "ASBNeither a borrower nor a lender be: For loan oft loses both itself and friendAOIJ", you'll be very likely to destroy some useful text (and be selected against) long before you get to that weasel phrase.

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    1. I think the fuller context of John's comment would be "[given the existence of meiosis/diploidy, reduced net metabolic costs, packaging mechanisms, multiple origins of replication and smaller population sizes in eukaryotes vs prokaryotes all leading to reduction of the selection pressure against 'extra' DNA,] even an OEC would need to postulate some sort of divine intervention to keep junk from entering the [eukaryote] genome".

      As soon as you open up a region that cannot suffer a deleterious mutation, you create a space where the bacterial 'deletion' argument loses traction. Such regions can grow, subject only to counter-selection on metabolic cost.

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    2. And in which case, in order to even make the metabolic cost-argument, that cost would have to be calculated in order to determine whether it was in fact strong enough to be selected against under "normal" living conditions of the organism.

      This also seems to highlight an area of potential study: Has anyone actually tried long-term evolution experiments with say, Yeast (like Saccharomyces cerevisiae), under close to starving conditions, to see if there is gradual genome shrinkage due to loss of junk regions? Is that even a feasible experiment or am I missing something?

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    3. I actually managed to find a study trying to determine the adaptive benefit of gene-loss in Yeast:
      http://www.pnas.org/content/102/49/17670.full.pdf+html
      Loss of dispensable genes is not adaptive in yeast

      Abstract
      A substantial share of genes identified in yeast can be deleted without visible phenotypic effects. Current debate concentrates on the possible roles of seemingly dispensable genes. The costs of maintaining unnecessary functions has attracted little attention. The hypothesis of antagonistic pleiotropy postulates that adaptations to different constituents of the environment are likely to interfere with each other, and therefore loss of unnecessary functions is potentially advantageous. We tested an entire collection of nonessential yeast gene deletions in a benign and nutritionally rich environment in which the number of dispensable genes was particularly high. We applied a series of competition experiments that could detect differences in relative fitness of ~0.005. No beneficial deletions were found, except perhaps for the deletion of about a dozen genes that slightly improved competitive ability; however, a functional explanation of the fitness advantage is lacking. The paucity of beneficial gene deletions is striking because genetic adaptations to laboratory conditions are regularly observed in yeast. However, it accords with the finding that the gene contents of four species of Saccharomyces are nearly identical, despite up to 20 million years of independent evolution and extensive DNA sequence divergence. Such extreme conservation of functions would be improbable if there were periods of selection promoting the loss of temporarily dispensable genes. The evident cohesion of the yeast genomes may be their evolved feature or an intrinsic property of complex genetic systems.

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    4. So they were just looking at genes not neccessarily loss of non-translated / non regulatory bits? (Seems to me that whole genome analysis would be necessary to analyze the benefits of getting rid of excess sequence. Those would be very interesting experiments indeed!)

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    5. Yeah they were only looking at genes. But genes are, like junk would be, just more DNA sequence with metabolic cost of production and maintenance. If getting rid of excess DNA would yield an adaptive benefit, it should have shown up in this study.
      Well, I guess you could always ask whether they removed enough of it to make a difference. But then the IDiot arguments would become even more convoluted, because ID would then have to accept the possibility of *some* amount of junk being possible, below a certain threshold. So how much junk does ID allow and how does this amount of junk invariably follow from ID and not merely an evolutionary mechanism?

      That's the million dollar question they'll never answer.

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    6. Possibly, but I can see the argument that you should look first at noncoding sequence for evidence of adaptive loss if the main metabolic cost of the "junk" is in replication (or possibly transcription - it would be equally interesting to see if there is a change in the % of the "junk" genome that is transcribed - we know that certain genes are down regulated in starvation conditions, but do we know whether any of this seemingly extraneous junk is blocked at the transcription level under poor conditions? (Again, I'm not a molecular biologist, so my knowledge of the literature is fairly cursory)

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    7. Testing these deletions in a nutritionally rich environment would potentially mask a selective effect on the DNA cost itself. Of course, even if such an effect were observed, one would have to assume that nutritional limitation was the norm for long periods of evolutionary history before the 'intuitive' expectation, that DNA is sufficiently costly to select for significant losses of nonfunctional regions, could be supported.

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  13. @coco
    That's another interesting possibility, and indeed, if there is already regulation of this junk in place, you'd expect downregulation of junk transcriptions before you start seeing large amounts of deletions just due to random mutations.

    @Allan Miller
    Yes the thing about the nutritionally rich environment caught my eye too. To really try and "bring out" the possible effect selection could have on replicating, maintaining and transcribing junk, you'd have to limit the nutrients used for this. But as you say, since you'd expect there to have been lots of periods of limited nutrients during the course of evolution, the fact that there is any junk at all suggests whatever metabolic cost this junk has, is so low as to be almost invisble to selection.

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  14. JM at ENV: “the prized 98% sequence-identify figure between humans and chimpanzees relates to the 2% of DNA that codes for the production of proteins. The non-protein-coding regions of DNA are far more species-specific. If these stretches of non-coding DNA really are functional, then what becomes of this sequence-identity figure and its significance with respect to shared ancestry?”

    Since overall figures of 98%+ have been coming out since pre-sequencing DNA hybridisation studies, which cannot distinguish anything but raw sequence, I'd say that 'proteins-only' claim is wrong.

    He also says that the genome is pervasively transcribed into mRNA

    Sigh.

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