Wednesday, July 08, 2009

Junk DNA and the Scientific Literature

 
A discussion about junk DNA has broken out in the comments to Monday's Molecule #128: Winners.

Charlie Wagner, an old talk.origins fan, wonders why junk DNA advocates are still around given that there have been several recent papers questioning the idea that most of our genome is junk.

Charlie asks ...
So why are Larry and many others still clinging to the myth of "junk DNA"? Do they not read the literature?
Of course we read the literature, Charlie, but unlike you we read all of the literature. You can't just pick out the papers that support your position and assume that the question has been settled.

The skill in reading the scientific literature is to put things into perspective and maintain a certain degree of skepticism. It's just not true that everything published in scientific journals is correct. An important part of science is challenging the consensus and many scientists try to make their reputation by coming up with interpretations that break new ground. The success of science depends on the few that are correct but let's not forget that most of them turn out to be wrong.

THEME

Genomes & Junk DNA
The trick is to recognize the new ideas that may be on to something and ignore those that aren't. This isn't easy but experienced scientists have a pretty good track record. Inexperienced scientists may not be able to distinguish between legitimate challenges to dogma and ones that are frivolous. The problem is even more severe for non-scientists and journalists. They are much more likely to be sucked in by the claims in the latest paper—especially if it's published in a high profile journal.

Lots of scientists don't like the idea of junk DNA because it doesn't fit into their view of how evolution works. They gleefully announce the demise of junk DNA whenever another little bit of noncoding DNA is discovered to have a function. They also attach undue significance to recent studies showing that a large part of mammalian genomes are transcribed at one time or another in spite of the fact that this phenomenon has been known for decades and is perfectly consistent with what we know about spurious transcription.

I've addressed many of the specific papers in previous postings. You can review my previous postings by clicking on the Theme Box URL. The bottom line is "don't trust everything you read in the recent scientific literature."

Another good rule of thumb is never trust any paper that doesn't give you a fair and accurate summary of the "dogma" they are opposing. When you challenge the concept of junk DNA, for example, it's not good enough to just present a piece of new evidence that may not fit the current "dogma." You also have to deal with all the evidence that was used to create the consensus view in the first place and show how it can be better explained by your new model. A good place to start is The Onion Test.


The figure is from Mattick (2007), an excellent example of what I'm talking about. This is a paper attacking the current consensus on junk DNA but in doing so it uses a figure that reveals an astonishing lack of understanding of genomes. This makes everything else in paper suspect. The figure was chosen by Ryan Gregory to be the classic example of a Dog's Ass Plot.

Mattick, J.S. (2004) The hidden genetic program of complex organisms. Sci Am. 291:60-67.

33 comments :

  1. Nature Genetics 41, 563 - 571 (2009)
    Published online: 19 April 2009 | doi:10.1038/ng.368

    The regulated retrotransposon transcriptome of mammalian cells

    Geoffrey J Faulkner1, Yasumasa Kimura2, Carsten O Daub2, Shivangi Wani1, Charles Plessy2, Katharine M Irvine3, Kate Schroder3, Nicole Cloonan1, Anita L Steptoe1, Timo Lassmann2, Kazunori Waki2, Nadine Hornig4,5, Takahiro Arakawa2, Hazuki Takahashi2, Jun Kawai2, Alistair R R Forrest2,6, Harukazu Suzuki2, Yoshihide Hayashizaki2, David A Hume7, Valerio Orlando4,5, Sean M Grimmond1 & Piero Carninci2

    Abstract

    Although repetitive elements pervade mammalian genomes, their overall contribution to transcriptional activity is poorly defined. Here, as part of the FANTOM4 project, we report that 6–30% of cap-selected mouse and human RNA transcripts initiate within repetitive elements. Analysis of approximately 250,000 retrotransposon-derived transcription start sites shows that the associated transcripts are generally tissue specific, coincide with gene-dense regions and form pronounced clusters when aligned to full-length retrotransposon sequences. Retrotransposons located immediately 5' of protein-coding loci frequently function as alternative promoters and/or express noncoding RNAs. More than a quarter of RefSeqs possess a retrotransposon in their 3' UTR, with strong evidence for the reduced expression of these transcripts relative to retrotransposon-free transcripts. Finally, a genome-wide screen identifies 23,000 candidate regulatory regions derived from retrotransposons, in addition to more than 2,000 examples of bidirectional transcription. We conclude that retrotransposon transcription has a key influence upon the transcriptional output of the mammalian genome.

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  2. This comment has been removed by the author.

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  3. Thanks for your reply. It didn't say what I would have liked it to say, but the advice is sound.
    Above is another paper dealing with retrotransposons.

    (note the recent date)

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  4. Reading the very brief links would have yielded a particularly pointed clue:
    'Some non-coding DNA certainly has a function at the organismal level, but this does not justify a huge leap from "this bit of non-coding DNA [usually less than 5% of the genome] is functional" to "ergo, all non-coding DNA is functional".'

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  5. Yet another symptom of what should be called "Evolutionary Creationism" -- this belief, quite common even in the scientific community, that evolution has 'designed' everything with goals and plans in mind. Essentially replacing the 'Intelligent Designer' with a less intelligent one. I don't see it fundamentally as much of an improvement...

    "But how could there be crap in our genomes! Nature has a purpose for everything! Look how well-designed the bird's wing is!" Etc... blergh.

    Of course, one mustn't dismiss things too quickly, so perhaps 'junk' was a bit of a dangerous term (media at work again). Perhaps 'evolutionary/genomic noise' could have been less dismissive?

    Cheers,
    -Psi-

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  6. "Can I explain why an onion needs about five times more non-coding DNA for this function than a human?

    It doesn't NEED it...

    It's STORING it.

    Why does a yeast cell have >6000 genes?

    Evolution draws from (or has drawn from) a pool of pre-existing genetic materials.

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  7. Look, sure i don't NEED those 2000 empty beer bottles in my house... but they're not junk, i'm just STORING them! That's right hon', the kids might need 'em.

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  8. "Reading the very brief links would have yielded a particularly pointed clue:"

    Where can these "very brief" links be found?

    Where does this quote come from?

    Cite, please.

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  9. "Look, sure i don't NEED those 2000 empty beer bottles in my house... but they're not junk, i'm just STORING them! That's right hon', the kids might need 'em."

    Right. And Windows XP doesn't "need" all that excess code.

    Until it needs it.

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  10. You're kidding right? I mean, if you had read the page on the onion test, "cited" in the article we're discussing, it's a quote right there from footnote 2. You don't even have to scroll much. Yes, they are brief articles.

    And look, stop being silly. *You* drew a disctinction between needed and stored, and you said that those genes weren't all needed. I just happened to point out you were dancing around the word junk. I don't care if those sequences were put in there by aliens from Xanax 3, if they're not needed by that organism they're junk. They might be useful junk for later generation or might happen to activate in some future mutation or were once useful to its owning organism, but again that's just cute footwork.

    And your analogy with windows fails on several levels. First, windows does contain junk code--not just technically "dead code" that's entirely useless, but it's also because it really is a lot of bloated junk code that's useless. It also happens to be a piece of junk. A better but still lacking analogy is to consider the OS when it's loaded in memory (live). If you were to scan the whole executable memory, you'd find lots of bytes with valid operator. Yet most by far would never be executed or be executable.

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  11. ...(some ancestral)* owning organism...

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  12. T. Ryan Gregory is an evolutionary biologist. I read some of his papers and looked at his website. I don't get the impression that he is unbiased, rather I get the impression that he is a darwinian zealot. He (or you) should feel free to correct this impression if it is wrong.

    More to the point, I read (with great difficulty, I might add because my 65 year old eyes are failing) the linked paper and I discovered that it is from 2000.

    A lot has happened since then.

    There is now sufficient evidence to conclude that most of the DNA and RNA is functional and necessary for effective genome function.

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  13. Anonymous wrote:

    "'Some non-coding DNA certainly has a function at the organismal level, but this does not justify a huge leap from "this bit of non-coding DNA [usually less than 5% of the genome] is functional" to "ergo, all non-coding DNA is functional".'



    "There's been a quiet revolution taking place in biology during the past few years over the role of RNA," says Dr Alexandre Akoulitchev, a Senior Research Fellow at the University of Oxford. "Scientists have begun to see 'junk' DNA as having a very important function. The variety of RNA types produced from this "junk" is staggering and the functional implications are huge."

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  14. Cite for the quote above:

    http://www.wellcome.ac.uk/News/Media-office/Press-releases/2007/WTX035515.htm

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  15. A list of papers contradicting Larry's view here: http://biopinionated.com/2008/10/28/hammering-nails-in-the-junk-dna-coffin/

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  16. Nils Reinton says,

    A list of papers contradicting Larry's view here: ...

    We've discussed this list before.

    I find it very interesting that you say ...

    Also and importantly, I have not myself had the time to review these articles as thoroughly as I would have wanted to, – some have been read carefully, others lightly and yet others just skimmed through.

    In other words, you've just collected a bunch of papers that express some degree of skepticism about junk DNA but you couldn't be bothered to read them carefully to see if they meet the criteria of good science.

    Nils, nobody is denying that there is a controversy in the scientific literature. Pointing that out by publishing a list of papers that agree with you isn't very helpful, especially since I've already posted discussions on some of those papers.

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  17. Charlie Wagner says,

    T. Ryan Gregory is an evolutionary biologist. I read some of his papers and looked at his website. I don't get the impression that he is unbiased, rather I get the impression that he is a darwinian zealot. He (or you) should feel free to correct this impression if it is wrong.

    Gregory is not a "Darwinian zealot" by any reasonable definition of that term. As a matter of fact, the concept of junk DNA is anti-Darwinian and it's the opponents of junk DNA who tend to be Darwinian zealots.

    A lot has happened since then.

    Not really. That's the whole point of my post. There has always been opposition to the concept of junk DNA and that hasn't changed. The only thing that's changed is that recent opposition papers are worse than those published ten or twenty years ago. Back then there was a much more legitimate controversy because we didn't have eukaryotic genome sequences.

    Modern opposition papers are deliberately ignoring much more evidence in support of junk DNA than their predecessors. This makes them worse.

    There is now sufficient evidence to conclude that most of the DNA and RNA is functional and necessary for effective genome function.

    I don't agree and neither do lots of other scientists. Do you really think we're too stupid to recognize the evidence?

    There is still a very active controversy over this issue. I have a very strong opinion about which side is correct and I'm more than willing to debate anyone who is reasonable.

    But it's completely unreasonable to simply declare that junk DNA opponents have won the day and the controversy is over. You don't convince anyone by just publishing a list of opinions from the other side.

    That's something that you need to stop doing if you want to engage in serious discussion. Same goes for that kook, András Pellionisz.

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  18. "As a matter of fact, the concept of junk DNA is anti-Darwinian

    Huh? NOT!

    For decades, darwinian evolutionists argued that "junk DNA" was "molecular
    garbage, junk left over from millions of years of evolution". ...

    "Not really. That's the whole point of my post."

    Huh?

    You simply cannot read the current literature and say that.
    My conclusions are informed by the peer-reviewed literature and reflect the most recent work.

    You seem to be stuck in some kind of time warp.

    Can you cite any papers in the last 5 years that support the notion that most of the genome is non-coding?

    "I have a very strong opinion about which side is correct and I'm more than willing to debate anyone who is reasonable.

    It's hard to debate with someone who claims that up is down and black is white and refuses to acknowledge the facts.

    It would be like debating with a creationist or cult member.

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  19. Larry. Yes, we have discussed this before, and I find these discussions scientifically rewarding. The list isn't really meant for you, but to serve as background for others that otherwise would be buying into your junk-argumentation. I am reasonably certain that there's some pretty good science in that list !! If anyone feels otherwise on any or all of the listed papers, they are most welcome to comment on the post and I'll gladly publish that comment. I can also link to any/all of the sandwalk-posts you feel should be mentioned - just send me the links if you think including those will make the list more "helpful". This idea of 90 % junk that you keep clinging on to will fade away regardless, I'm sure.

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  20. Nils-- I'm curious about the "90% junk" comment. If this hints that it's just quibbling about different non zero/trivial percentage then that's of very little interest to me.

    The discussion really is about something else. Do you think the percentage of junk sequence is 0%? In other words, is it your position that all DNA of all living things only includes sequences that are active and useful. If so, do you suppose that this implies a weeding mechanism with near perfect efficiency? Or that no sequence once acquired in a lineage ever become obsolete or useless?

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  21. Anonymous. This is a question for Larry really, - he's the one who holds the 90% junk position. Yes this is "quibbling about different non zero/trivial percentage", but I do not think Larry's 90%-junk arguments are trivial. I am confident that there's "junk" in our genome (my guess would be 10% or less, but that's just a guess), - I am confident that the majority isn't junk, - and that much of what has been believed to be junk will be proven to have some kind of function. This is what the references in the above mentioned list aims to document, and what Larry refuses to acknowledge. My main criticism towards the junk-people though, is that calling something "junk" stands in the way of doing potentially interesting experiments to find novel functions for these pieces of DNA.

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  22. Dear, 10%, 90%, the basic idea is the same and we're basically debating vanilla vs chocolate. Personally i would imagine that this would vary tremendously between different species (ie some can have lots of junk and some might have very little, all semi-random). So what if it's on the low end or the high end for some particular species? It's the people that argue perfect efficiency (/wink purpose & design), usually exclusively for humans, that puzzle me.

    I disagree that the "junk" label has had a negative impact. I'd argue quite the reverse actually. It's been a great gauntlet thrown down and that attracts people. There is a certain fame that attaches all the more to discoveries of some function or usefulness to sequences previously labeled junk. Anyway, lots of people argue for the term "noncoding" (perhaps with loss of some scope), and it wouldn't be the first misleading term in science... a word in the linguistic register of science is free to have a different meaning than it does in plain english.

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  23. Sorry, couldn't put my finger on something and then figured it out. I don't think you can have it both ways here:
    (1) "calling something "junk" stands in the way of doing potentially interesting experiments to find novel functions for these pieces of DNA"
    (2) "much of what has been believed to be junk will be proven to have some kind of function" combined with all "the references in the above mentioned list"

    If point (1) is the main criticism, then it's severely undercut by your point (2). The on going research and publications are evidence for my argument against (1).

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  24. So do transposons qualify as 'junk'? I believe I've heard some organisms have shitloads of those!


    Some non-coding DNA can carry structural function, so perhaps in that way that particular sequence can be classified as non-junk (although if that sequence wasn't there in the first place, perhaps the structural problem would have been dealt with in some other way?)

    A good argument against 'most DNA has function' is the ciliate genome rearrangement case. Ciliates have two types of nuclei - germline (heritable) and somatic (destroyed upon each conjugation and reformed). Interestingly, upon forming the somatic 'macronucleus' (MAC) from the germline 'micronucleus' (MIC), vast expanses of the MIC genome are deleted, known as IESs (internal eliminated sequences) vs ones that remain behind - MDSs (MAC destined sequences). To some extent, the IES and MDS act analogously to introns and exons, respectively, albeit on the genomic level.

    Furthermore, what is excised upon the formation of the new MAC depends on the MDSs present in the old MAC. If you insert a foreign gene into the MIC, it will not make its way to the MAC; whereas if you stick an IES into the old MAC, it will no longer be excised.

    This mechanism uses strikingly similar machinery to epigenetic silencing, which has partly evolved (and also enabled) due to transposon invasions. Ciliates can be viewed as a case of transposon defense gone haywire!

    Their close relatives dinoflagellates also have screwed up genomes - about 10x the size of the human one in cases. (and not as many genes, by far) This means we don't yet have any dino genome sequences, but it would be very interesting to see whether they too are some transposon defense mechanism gone wild - some have speculated that the non-coding DNA has a structural role. Perhaps the dino strategy was to use the parasitic sequence invasion for structural purposes.

    Both cases show strong evidence that some, if not much of, non-coding DNA could be lived without; probably just a byproduct of replication errors and transposon activity (some of which can become 'useful' by evolutionary accident). However, I don't see what the point of the fierce argument above is. The terms 'useful' and 'useless' have very little significance in evolution, unless we recognise that they're just shorthand for "we found'/'haven't found and likely never will' an evolutionary cause for this feature being conserved". Evolution lacks intentionality, and thus any usefulness and uselessness is just an artefact of human reasoning.

    Stuff just is -- evolution could care less whether there is some use for it or not; the organism either reproduces and thus still exists, or fails to reproduct, and thus no longer exists. Everything else is just a byproduct of our 'intentional stance'.

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  25. Anonymous. Yes, "we're basically debating vanilla vs chocolate". Further, I'll assume you are right that "[junk] has been a great gauntlet thrown down and that attracts people.". Those are good points and I'll stop debating, as it seems this discussion has come to the right conclusion: we currently do not know how much of our genome we can define as junk, and we'll keep on doing experiments to find out. Hopefully Larry reaches this conclusion as well and stops his sometimes unfair verbal attacks on those publishing results of such experiments.

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  26. Nils Reinton says,

    I am confident that the majority isn't junk, - and that much of what has been believed to be junk will be proven to have some kind of function. This is what the references in the above mentioned list aims to document, and what Larry refuses to acknowledge.

    It's not correct to say that I have "refused to acknowledge" the claims you reference.

    I believe I have addressed all of the significant claims purporting to show that most of our genome is functional. If you can think of an important claim that I've ignored then this is your chance to mention it.

    If you can't, then I'll accept your apology.

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  27. Larry. I am saying that you refuse to acknowledge the conclusion most others are drawing from my list of references which is: "most of our genome is not junk", - you keep drawing the opposite conclusion.

    I assume you do not need an apology for me saying this.

    "I believe I have addressed all of the significant claims purporting to show that most of our genome is functional."

    I too believe you have done this. My apologies if you interpreted my comment as saying that you are not thorough - I honestly think you are, ...too much so when it comes to this subject.

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  28. I do not draw the conclusion that "most of our genome is not junk"; to quote someone i read: "In the absence of any reasonable functional explanation [...] it is reasonable to adopt the working hypothesis that they are junk. That's not a science stopper. It's just common sense." Starting with the presumption that things we have no clue as to their function has one seems to be the opposite way of doing science right.

    If we go about this the way it seems you're suggesting, you say it has function, i ask why... and you say because we'll find one eventually? The way i take Larry to be suggesting, i say it has no function, you ask why; i can say it's because it's non-coding, eg.

    At this point you can come back and show that it does transcribe in some weird cases, or that it creates spacers in between gene sequences that allow room for enzymes, or have some brilliant novel explanation. And we can discuss the evidence for that then.

    So much for approach. Ultimately however, i'm puzzled. What does it matter if the human genome has 10%, 45%, 55%, 90% junk? What useful information do we get from particular number? Are there theories that would be proven right or wrong based on that?

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  29. Nils Reinton says,

    Larry. I am saying that you refuse to acknowledge the conclusion most others are drawing from my list of references which is: "most of our genome is not junk", - you keep drawing the opposite conclusion.


    OK, I see the distinction you are making.

    But what's the point? I assume you would say the same thing about the people who published the papers in your list. Don't they "refuse to acknowledge" the opinions of junk DNA proponents?

    How helpful is it to point out that nobody on either side is prepared to concede victory at this time?

    BTW, among those people who have kept up with the literature and the debate, I'm not sure it's correct to say that "most others" agree with your position.

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  30. When I saw the phrase "onion test", I assumed it had something to do with whether the idea would show up on The Onion website. I'm sure I've seen at least one dog's ass plot there?

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  31. When a scientist finds a function for a piece of DNA formerly dismissed as "junk," that's cool science!! Why not celebrate it? Who cares what it means for ID-ers or whether use of the term "junk" is appropriate or whether x, y, or z is "Darwinian"? We're going to be seeing a lot more of these discoveries in the coming years. There is some very cool work being done with transposable elements in particular.

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  32. Anonymous asks,

    When a scientist finds a function for a piece of DNA formerly dismissed as "junk," that's cool science!! Why not celebrate it?

    I have no problem with that. I think it's cool.

    However, when the authors of the paper go on to say that all DNA must have a function, that's not cool. I don't celebrate such statements because it's bad science.

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  33. However, when the authors of the paper go on to say that all DNA must have a function, that's not cool. I don't celebrate such statements because it's bad science.

    Does this ever happen? The authors actually say "all DNA must have a function" or equivalent language? Got a citation for a paper that says that?

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