Tuesday, December 06, 2011

PZ Myers Talks About Junk DNA

 
PZ Myers has a blog called Pharyngula—perhaps you've heard of it?

He gave a talk on junk DNA at Skepticon IV in Sringfield, Missouri (USA) a few weeks ago. I disagree with a few thing he said,

1. Some intron sequences are essential for splicing whereas PZ implies that they are all junk.
2. Regulatory sequences make up less than 1% of your genome and not more than exons as PZ says [What's in Your Genome?].
3. Half or your genome is DEFECTIVE transposon, not active transposons. Active transposons are not junk. Defective transposons are a form of pseduogene and they are definitely junk. The distinction is important.

But the main point is that the IDiots predicted there wouldn't be any significant amount of junk in your genome and that prediction has been refuted.




37 comments :

  1. PZ is a molecular biology illiterate and buffoon. He hasn't published a research article since 1998. As well as having a role in AS, introns are known to contain many important enhancers and silencers that may have been donated through the insertion of transposable elements.

    However, I fundamentally disagree with Professor Moran too. "Defective" or "inactive" transposons can, of course, be reactivated by mutation or recombination - as indeed can all pseudogenes. Larry may regard them as junk whereas I regard it as dormant or latent.

    Also, even if not jumping around the genome, these repetitive sequences might play a regulatory or compensatory role over a long distance, as some papers have indeed revealed.We need to conduct more research, not less.

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  2. I may disagree with your claim #3, i.e. that active transposons aren't junk. From the point of view of the genome, they are, and we can tell this because their sequences are not conserved by selection. To the organism, they're junk. To themselves, they aren't, but the only selection they're subject to is a sort of population process within the genome: sequences that get inactivating mutations become inactive and stop reproducing.

    Maybe a slight disagreement on point #1 too. Those splice signals and occasional other regulatory sequences make up such a tiny part of the typical intron that as a first approximation we can ignore them.

    You're still allowing Atheistoclast to spew, eh?

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  3. Thank-you Atheistoclast for the "Junkyard Wars" view of biology.

    http://www.tv.com/shows/junkyard-wars/

    I'm sure Fugu and Drosophila will be sad to hear that they have less "latent" or "dormant" genetic material. (Funny - they seem to do quite well without it...). And why have the salamanders not become the pinnacle animal species?

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  4. Bullshit Clastie, this is just another example of you making up whatever shit you find convenient.

    You have been seen arguing in the past that evolution is only "degenerative" and that "natural selection can only conserve, it cannot create".

    Now suddenly you're arguing that nonfunctional sequence CAN become functional(which, I might add, still doesn't give it function now) by mutation and recombination, and thus you seem to have reversed your earlier position.

    Which is it then? Can evolution create or not?

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  5. While I can't speak to the biology involved here, I can certainly point out that one property of junk is that it can be recycled - so I don't quite see what the difference is supposed to be between calling it "junk" or "latent/dormant", unless you're trying to imply that there's some explicit mechanism that uses this to temporarily disable some sequences (as opposed to random processes producing this as a side effect) - an I don't think that's what you're trying to imply.

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  6. "Defective" or "inactive" transposons can, of course, be reactivated by mutation or recombination - as indeed can all pseudogenes."

    Can you please calculate the dFSCI for that? That would really great to know what a single mutation can do.

    And it´s always nice to see how IDiots are starting to soften their claim (there is no junk dna) by the introduction of latent or dormant specified complex information ^^ (LSCI would make a nice acronym)

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  7. I suspect much of the 3'UTR can be deleted without any consequence. Does that it make it "junk" too?

    Introns are useful spacer sequences. However, I think mutations in them can destablize the mRNA transcript.

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  8. Atheistoclast wrote: "Introns are useful spacer sequences. However, I think mutations in them can destablize the mRNA transcript."

    And you'd be working in a laboratory to explore the validity of this assertion, ready to accept the implications of you possibly being wrong on this, right? No? You're just another internet nobody why's main objective is to make rethorical, apoligist shit up to propagandize for doctrine you say? I'm so surprised.

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  9. "But the main point is that the IDiots predicted there wouldn't be any significant amount of junk in your genome and that prediction has been refuted."

    Won't matter to the IDiots, they have fingers in both ears while they chant NA NA NA NA NA NA NA ...

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  10. Rumraket said...

    You have been seen arguing in the past that evolution is only "degenerative" and that "natural selection can only conserve, it cannot create". Now suddenly you're arguing that nonfunctional sequence CAN become functional... by mutation and recombination... Which is it then? Can evolution create or not?

    FTW. :)

    The kind of ass tread marks Roadkilloclast acquires in every discussion here, per my previous observation.

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  11. Introns do affect gene expression. A mutation in an intron is responsible for the reduced expression of melanin in the eye - resulting in a blue appearance.

    Surveys have shown that intronic sequences (which include retrotransposon insertions) are evolutionary conserved.

    Sorry, but I am right.

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  12. @Atheistoclast ... Yeah, I'm a latent millionaire. I'm just not a millionaire right at this moment ... I'm also a latent homosexual. I'm just not a homosexual right now ... and I'm a latent member of Al Quaeda ... my garbage is a latent sculpture. And so on.

    Regardless, whoever advocated conducting less research?

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  13. Predictably, perhaps, the folks at Uncommon Descent have picked up on this again.

    However, their argument against PZ's case for junk DNA begins and ends with Myers's self-description as the Paris Hilton of athiesm.

    Good arguing, guys.

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  14. Against my better judgment...

    Atheistoclast, that bit about blue eyes is interesting. Can you provide a citation for that?

    And the bit about conservation of intron sequence is either garbled or false. Can you provide a citation for that?

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  15. Hey, atheistoclast actually provided a couple of interesting citations.

    An upstream regulatory sequence for a gene affecting eye color is located in an intron of another gene, and as much as 28% of the sequence in some mammalian introns is conserved more than expected under a neutral model and is therefore probably under some degree of selective constraint. Cool.

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  16. John,

    It doesn't matter how many papers I cite. Larry just isn't interested. He is 'Professor Junk DNA' and will remain so until further notice.

    Most competent researchers in the field are in fact deeply interested in the functional potential (however peculiar) of both intragenic ncDNA (introns) and intergenic ncDNA which contains lots of retrotransposon insertions.

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  17. John Harshman says,

    An upstream regulatory sequence for a gene affecting eye color is located in an intron of another gene, and as much as 28% of the sequence in some mammalian introns is conserved more than expected under a neutral model and is therefore probably under some degree of selective constraint. Cool.

    I agree that those are cool examples of functional sequences within introns.

    There are even better examples. There are some introns in some genes in some species that contain entire functional genes.

    None of this changes the conclusion that most intron sequences are junk and that most of our genome is junk. It's this last part that the creationists have trouble with. They get really confused about the difference between forests and trees.

    I don't want to censor anyone on Sandwalk but that doesn't mean I have to pay attention to them. Neither should you.

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  18. Larry says:None of this changes the conclusion that most intron sequences are junk and that most of our genome is junk. It's this last part that the creationists have trouble with. They get really confused about the difference between forests and trees.

    This epitomizes Larry's complete lack of any understanding. Just because large swathes of ncDNA have no apparent function does not mean that they can necessarily be considered "junk". They needn't be as critical as the protein-coding stuff.

    How much of the Untranslated region (UTR) - which Larry does not regard as junk - can be deleted without consequence? Probably quite a bit. Does it mean it is junk? No. The benefits it bestows are more subtle, such as in conferring mRNA stability etc.

    I am flabbergasted by Dr. Moran's anti-scientific attitude. He wants to preclude any investigation into the possible functions of most of the genome on the grounds that it must be junk because he is not smart enough to see how it could be anything other than junk.

    Larry will almost certainly be proved wrong, but it will take a lot of time and effort. In the meantime, he continues to mis-educate his students and his readers here. This is absolutely appalling. I intend to make a formal complaint to his university.

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  19. I advise anyone who is actually interested in introns (and their evolution) to read this excellent summary about the known, and possible, functions for the intragenic elements:

    Introns in gene evolution

    A little science goes a long way.

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  20. PZ is a molecular biology illiterate and buffoon.

    Agreed. He has got a nice beard though, and you can't argue with that.

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  21. Larry,

    Actually the annoying one's second citation (Hare & Palumbi 2003) makes the case that only a bit over 2/3 of the average intron is junk. Would you call 2/3 "most"? Perhaps. But not as much "most" as I had previously supposed. (Caveat: small sample.) A stopped clock is right twice a day; well, that used to be true before everything went digital.

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  22. John says: "a bit over 2/3 of the average intron is junk."

    No, that is not what it means. Just because the sequence of an intron is not conserved does not make it "junk". You might as well say that the exons of many duplicate genes are "junk" because there is appreciably less selective constraint on them than there is in the case of singletons.

    My hypothesis is that introns are primarily spacer sequences used to divide genes up and so facilitate both exon shuffling and alternative splicing (i.e. exon skipping). They need to be fairly long. They probably also protect the protein-coding part against retroviral attacks though their mere presence. As such, much of their sequence is flexible.

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  23. My hypothesis is that introns are primarily spacer sequences used to divide genes up and so facilitate both exon shuffling and alternative splicing (i.e. exon skipping). They need to be fairly long.

    Introns in most eukaryotes are not "fairly long". They are, however, discarded like so much, um, er, junk.

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  24. @Atheistoclast;

    RE: introns and eye colour. You know well that in biology all things, regardless how weird, are possible. Of course genomes littered introns will end up using them.But the fact that any molecular event can have a "function", it does not mean that all of them do.

    I would hope that everyone would point out my logical flaw if I started talking about overthrowing the "central dogma of meiosis" due to the oddities of meiosis in some Diptera.

    Journal of Heredity (1988) 79, 3 Pp. 190-199.
    Abstract
    Chromosome number and morphology in the germ line of the Hessian fly, Mayetiola destructor(Say), were examined with orcein- and silver-staining and C-banding techniques. Spermatogenesis and oogenesis through early prophase I also were examined. The germ-line genome consisted of a set of S (somatic) chromosomes and a group of E (eliminated) chromosomes, as defined by their morphology and cellular distribution. The S chromosomes in both male and female germ lines had a distinctive, negatively heteropycnotic centromere in the median position, stained intensely with orcein, and were entirely C-positive except for their centromeres. Four S chromosomes were consistently found in spermatogonial cells and secondary spermatocytes. Eight S chromosomes were found consistently in oogonial cells. These observations and the results of mating experiments indicated that the germ-line S chromosomes correspond to the somatic genome (n=4). S chromosome morphology, which was distinctly different between germ-line and somatic cells, Indicated that only the matermally derived S genome is physically modified in the male germ line, whereas both parental S genomes are modified in the female germ line. E chromosomes, which were variable in morphology and number, were restricted to the germ line and did not correspond to any part of the somatic genome. Spermatogenesis was atypical in that all E chromosomes were eliminated at meiosis I, and only the maternally derived haploid set of S chromosomes was transmitted in the sperm. Ova probably contributed a haploid set of S chromosomes and a complete set of E chromosomes to each zygote.

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  25. I would be interested to see any research on the conservation, or otherwise, of intron size rather than the actual sequence. Hang on! Real scientists have already explored this:

    Evidence for intron length conservation

    Conservation of the sizes of introns

    Oops! I did it again....I guess I'm not that ignorant after all.

    It is time for Larry to accept he is wrong...graciously. But he is a stubborn Irishman who is set in his ways (as is Sean Carroll).

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  26. Dear a clast:
    What you present as evidence are simply to isolated examples. Those papers do not privide evidence for widespread conservation of intron position or leghth.
    In fact, the paper by Ala-Kokko et al. indicates that their findings are peculiar to COL2A1 gene: intron sizes are NOT conserved in other collalen genes.

    What this discussion is about is the prevalence of such functions for introns. ¿Is intron leght conserved for a significant part (>30%) of an species genes? Isolated examples of this or that function are expected: once introns are there hitchhiking any functions, random functions, is only natural.

    What you should look for is not examples of several, various, different, functions for introns, but a single function present and conserved among all introns (or a significant part of them).

    We all agree that introns are spacers, and that they allow exon shuffling. But function is within exons, or the whole system anyhow, not in introns specifically. Centromeric DNA also has a function, but not a sequence-dependent one. That's not what the discussion is about, I think.

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  27. Wow, Failclast is STILL here and at it?

    Wish I had this kind of tenacity in life and science...

    The again, perhaps it correlates somewhat negatively with relevance and meaningfulness of one's statements.

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  28. Enrique,

    You seem to be, like Larry, accusing me of not seeing the forest from the trees. I am not stating that introns are as important as exons or in any way subject to the same degree of conservation. What I am saying is that there is growing evidence for multiple functions among introns and for a broad, albeit not widespread, conservation of both their sequence and length. I don't think we can establish a single universal function for introns other than for exon skipping/shuffling.

    This discussion arose because a certain gentleman called Paul Zachary Myers asserted that introns are useless junk that are spliced out prior to translation.

    Of course, anyone with any knowledge of molecular biology knows that the cell wouldn't be as stupid as to employ complex spliceosomes to remove sequences that served no purpose at all. Selection would handle this by simply favoring their deletion.

    Larry Moran is of the opinion that all the "junk" that has accumulated in the genome, and which presumably entails a metabolic cost associated with its replication, cannot be whittled down by mutations that delete it. Presumably he thinks that the genome will continue to acquire junk ad infinitum and that the percentage of coding DNA will continue to decline.

    He is just plain wrong.

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  29. The large abundance of defective transposons and the like in genomes of mammals indicate that the load of DNA replication or transcription is NOT a major selection constraint for those species.

    I cannot see a selective pressure for intron size reduction either in those organisms. Many recent gene duplications and inactivations indicate that generation of junk is not stopped at all.

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  30. Enrique,

    Gene duplicates that become inactive can remain fixed in the genome. However, many of these pseudogenes (including retrogenes) can also be reactivated. It is too soon to call them "junk". However, natural selection will generally ensure that chromosomes do not become excessively large as this would affect stability and the replication process.

    The fact is that large swathes of the genome are conserved among taxa - including introns and intergenic regions.

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  31. Hi Larry,

    Is the linked review a good article to read to get up to speed on this?

    http://genome.cshlp.org/content/early/2011/08/26/gr.116814.110

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  32. Atheistoclast said...
    "The fact is that large swathes of the genome are conserved among taxa - including introns and intergenic regions."

    Yet their loss in Fugu does not bother you? The fact they can be despensed with, but are not always deleted by a random process is not really a good arguement for conserved function...

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  33. Heh. The 3% regulatory DNA figure comes from developmental biologists, who have an interest in inflating that figure. I also think they are over-generous in the estimate, but for this talk I was bending over backwards to emphasize the amount that was functional.

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  34. @PZ,

    I usually don't pay much attention to developmental biologists. I'd advise you to do the same! :-)

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  35. Developmental biologists provide a great deal of insight into the mechanisms of genomic function (intron, exon; regulatory elements, transcripts, proteins, etc.). Most in the literature work on proteomics or, shown here regarding intronic sequences, comes from the use of cell lines or Drosophila (which im cool with). The way any of these work in vivo in a 3D environment may be significantly different from what in vitro experiments show.

    And introns do have a function, a regulatory function. I see there is no mention here of any non-coding miRNAs.... this intronic junk is very important for regulating gene expression, splicing, etc. 3'UTR interactions with intronically expressed microRNAs is knee deep in the literature. intronic sequences regulationg hox genes and thus axial patterning of vertebrates is also a biggie. All branches of biology integrate for a deeper story. Im a developmental biologist who also works on noncoding RNAs, gene regulation and also study the ecology of organisms in the jungle.. its hard to take these arguments on this page when they are supported by single examples... all different mechanisms and definitions for junk DNA are context dependent.. maybe junk in one intron but not another, thats the beauty of the complex genome (even if a junk-regulatory element is 250kb upstream of a target gene... you must also remember that they are temporally and spatially regulated to function in several ways)

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  36. anonymous says,

    And introns do have a function, a regulatory function. ... etc.

    Could you give me an estimate of how much intron DNA is functional in a typical mammalian genome, in your opinion?

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