Monday, August 22, 2011

Junk & Jonathan: Part 10—Chapter 7

This is part 10 of my review of The Myth of Junk DNA. For a list of other postings on this topic see the links below. For other postings on junk DNA check out the links in Genomes & Junk DNA in the "theme box" below or in the sidebar under "Themes."



Functions Independent of Exact Sequence

The title of Chapter 7 is "Functions Independent of Exact Sequence." This is potentially the most important chapter in the book because it should address some of the serious arguments for function in the genome. We already know that sequence is not conserved in the vast majority of the genome that we call junk so in order for it to have a function it must be due to the presence of built DNA. The chapter begins with a brief description of enhancers. Enhancers are DNA binding sites required for the regulation of transcription of a gene. In many cases a protein will bind to an enhancer and also make contact with the transcription initiation complex (RNA polymerase + factors). This contact can activate or repress transcription. DNA binding sites are small (less than 10 bp) and they've already been included under regulatory sequences in calculation of genome content. Nobody thinks they're junk. However, an enhancer sequence can often be some distance away from the binding sites of other proteins and their interactions create a loop of DNA. This mode of binding is well-known and has been extensively studied in many system including the lac operon [Repression of the lac Operon] The figure shows a model of the lac repressor boud to DNA to illustrate the minimum size of a DNA loop. This DNA should be included in the amount of sequence needed for an active promoter even though the sequence is irrelevant. When binding sites are 50 bp apart, that's sufficient to allow looping. Longer stretches are okay but not necessary. Most regulatory regions lie well within 1000 bp of the transcription start site and even if you include all of this sequence—which is unreasonable—it only amounts to less than 1% of the genome. There are some famous examples of enhancer sequences that are several hundred kb (>100,000 bp) from the start site but these are exceptions, not rules. There's no reason to suspect that all of the DNA in the loop is necessary for proper transcription regulation and Wells doesn't even attempt to offer one. Theme Genomes & Junk DNAThe next section of Chapter 7 discusses chromatin and the specific example is centromeres. There's no doubt in anyone's mind that a good part of centromeric regions are essential (i.e. not junk). I've estimated that it could be a high as 2% [Centromere DNA]. Nothing new here. He forgot to mention telomeres. The last section of the chapter is truly bizarre. It's title is "Non-Protein-Coding DNA Can Function as a Lens" and it quotes a 1979 study claiming that concentrations of heterochromatin in retinal cells can function as a lens in nocturnal animals. Presumably this heterochromatin consist mostly of non-sequence-specific DNA and it may explain why we have so much of it in our genome. I don't believe it because it doesn't explain why other animals have junk DNA and it isn't a very good explanation for large plant genomes. Wells concludes the chapter with,
So at all three levels of the genomic hierarchy, there is evidence for functions that are independent of the exact DNA (or RNA) sequence. Like the evidence for sequence-dependent functions, the evidence for sequence-independent functions is almost certain to grow as scientists continue to expand their research horizon beyond the limits of the Central Dogma. There is a lot more to the genome (not to mention the living cell) than the protein-coding sequences in DNA.
There certainly is more to the genome than protein coding DNA. We've known that for four decades and none of that essential DNA is called "junk." It's a shame that Wells doesn't mention this because his readers might get the false impression that Wells is on to something that scientists don't know. I'm sure he doesn't intend to deceive his readers, aren't you?

18 comments :

  1. One "function" of the simple amount of DNA is that it influences cell size. In a given cell type it seems to be that cell volume or mass is roughly proportional to the amount of DNA. Diploid cells in yeast are about 2x the volume of haploid and so on with tetraploid etc. This is a widely observed effect.

    An cell size is physiologically important because of the ratio of surface area to volume decreasing with size.

    Ryan Gregory (http://www.genomicron.evolverzone.com/ could tell us much more I'm sure.

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  2. The really obvious point is that DNA that does something independent of its sequence is obviously irrelevant for the claims about "specified complex information" that the IDists are making. The only information present is the length of the DNA and perhaps its base composition which would affect flexibility, which are trivial.

    It's not clear why Wells even bring the subject up at all.

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  3. "The last section of the chapter is truly bizarre. It's title is "Non-Protein-Coding DNA Can Function as a Lens" and it quotes a 1979 study claiming that concentrations of heterochromatin in retinal cells can function as a lens in nocturnal animals. Presumably this heterochromatin consist mostly of non-sequence-specific DNA and it may explain why we have so much of it in our genome. I don't believe it because it doesn't explain why other animals have junk DNA and it isn't a very good explanation for large plant genomes."

    Do you mean that you do not believe that "concentrations of heterochromatin in retinal cells can function as a lens in nocturnal animals"?

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  4. Anonymous writes:

    Do you mean that you do not believe that "concentrations of heterochromatin in retinal cells can function as a lens in nocturnal animals"?

    Reading in context, it appears Dr. Moran is expressing disbelief about the italicized portion of the following quote:

    "Presumably this heterochromatin consists mostly of non-sequence-specific DNA and it may explain why we have so much of it in our genome."

    Disbelief about this as an explanation makes sense in light of the presence of large amounts of heterochromatin in the genomes of diurnal animals and plants, to which Dr. Moran refers.

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  5. http://www.scribd.com/doc/17676936/Physics-World-How-Physics-is-Changing-Biology-200907
    "If this is already a surprising adaptation, then the second discovery is nothing short of stunning. Below the layers bridged by the Müller-cell array is the outer nuclear layer of the retina that the light still has to traverse. It turns out that, in nocturnal animals, the nuclei in these layers have an arrangement of chromatin – the material that forms chromosomes – that is unlike the one found in nuclei of any other cell type in the body or even in the same cells in diurnal animals. The DNA contained in a single nucleus is about 2 m long when stretched out. To fit into a 10 µm nucleus it is tightly wrapped around proteins and coiled up into chromatin. The chromatin with the genes not currently needed, called heterochromatin, is especially densely packed and stowed away at the nuclear periphery; while eu- chromatin, containing often-used genes, is more ac- cessible and found at the centre. This arrangement of chromatin is so universal that it can be called “conventional”. However, in the outer nuclear layer in nocturnal animals, the heterochromatin is at the centre and the euchromatin is on the outside. Given that denser heterochromatin has a higher refractive index, this unique inversion turns the nuclei from scattering ob- stacles into little microlenses that focus the light through the outer nuclear layer without much scatter- ing while maintaining a high signal-to-noise ratio. The improved transmission leads to an optical advantage for seeing at low light levels, which has apparently caused this massive rearrangement to occur during evolution. The complete restructuring is even more surprising given that the relative position of the genes with respect to the location of hetero- and euchro- matin is heavily implicated in the way that the cell regu- lates gene expression. This means that these nuclei have thrown the entire conventional nuclear machin- ery (tried and tested for hundreds of millions of years and conserved in all other cells) overboard in order to optimize their optical properties. There is no light- guiding gene in cells. The refractive index is a collec- tive property emerging at a different conceptual level – physics – and we are increasingly finding that the same applies to many other case studies of the cell."

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  6. http://cshperspectives.cshlp.org/content/2/3/a003889.full
    "A striking example of CT reorganization during terminal differentiation was recently shown by Solovei et al. (2009) in a study of the mammalian retina. In mammals adapted to nocturnal life, all heterochromatin becomes located in the nuclear interior during postmitotic terminal differentiation of rod cells, whereas all euchromatin is shifted toward the nuclear periphery. This transformation starts around day 6 post partum and takes several weeks for completion. Rod cells of mammals with diurnal life styles do not show such a chromatin reorganization. Their nuclei reveal the conventional pattern with heterochromatin enriched at the nuclear periphery and around the nucleoli, whereas euchromatin is mostly distributed in the nuclear interior. This global nuclear reorganization in rod cells of nocturnal species necessitates a profound reorganization of radial chromatin arrangements rather than a change of CT proximity patterns. Unexpectedly, the inverted pattern of rod cell nuclei in nocturnal mammals reflects an adaptation to vision in low light conditions. Because of the somewhat higher refractive index of heterochromatin compared with less condensed euchromatin, inverted nuclei act as micro-lenses, which help to channel photons to the photoreceptors."

    Moran seems to be saying that Wells mentioning this phenomena is "bizarre". Hard to say why Moran says that.
    But we are probably stuck with others speculating what Moran meant, because Moran (the mythical unicorn) has stopped answering the simple, basic questions he is asked.

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  7. Possibly Larry isn't answering because any moderately intelligent person without creationist blinders on can see the answer. Hint: is Wells trying to explain a reorganization of chromatin or the presence of lots of DNA in the genome? Additional hint: which is different between nocturnal and diurnal mammals?

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  8. The title of the chapter apparently is "Functions Independent of Exact Sequence"

    For some reason, Moran found it "bizarre" that the phenomena of heterochromatin in nocturnal animals should be found in such a chapter.
    This is another of those Moran bait and switch tricks.
    Does anybody get it?

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  9. Let's explain a bit further. Wells is trying to explain the origin of large amounts of DNA by bulk function. Claiming a particular bulk function for some DNA in some species doesn't explain the origin if other related species have the same sort of bulk DNA without that bulk function. If, for example I were to explain the existence of the bridge of my nose by saying it's there to support my glasses, which it does quite well, you could counter by noting that other people, even those without glasses, still have bridges on their noses. See now?

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  10. It is nice of John Harshman to fill in for Moran.
    And if all I wanted was John Harshman's opinion, that would be sufficient. But it isn't.

    Harshman, are you saying that you have read Wells and you have formed your opinion based on what he said?

    I have not read Wells, so we are all hostage to Moran's biased reporting of what is said.
    But I mention again that this is in a section entitled "Functions Independent of Exact Sequence".
    Presumably Wells is saying that the
    heterochromatin function in nocturnal animals is an example of a "Function Independent of Exact Sequence". And presumably his point is that Functions that are Independent of Exact Sequence can be non-junk.

    Which I take it is a very significant idea as it could apply to a lot of other sequences of DNA that we have not yet deciphered and have incorrectly classified as "junk".

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  11. @anonymous I have not read Wells, so we are all hostage to Moran's biased reporting of what is said.

    Unintentional humour I'm sure.

    So run along and read it.

    Don't hurt yourself in traffic. Remember to wear a helmet. Look both ways at intersections. Don't drool in public. Chew with your mouth closed. Light coloured clothing stains more easily.

    I mean really, what a doofus.

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  12. I can see why Larry gave up. IDiot.

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  13. This sounds reasonable:
    "So at all three levels of the genomic hierarchy, there is evidence for functions that are independent of the exact DNA (or RNA) sequence. Like the evidence for sequence-dependent functions, the evidence for sequence-independent functions is almost certain to grow as scientists continue to expand their research horizon beyond the limits of the Central Dogma. There is a lot more to the genome (not to mention the living cell) than the protein-coding sequences in DNA."

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  14. Anonymous writes:

    Presumably Wells is saying that the heterochromatin function in nocturnal animals is an example of a "Function Independent of Exact Sequence". And presumably his point is that Functions that are Independent of Exact Sequence can be non-junk.

    Oooh, very good. Now go back to Dr. Moran's post and see where his "biased reporting" says exactly that. Gosh, only a few days and you've managed to understand a part of Dr. Moran's original post. If you keep working for a month or so, maybe you'll grasp the rest of what Dr. Moran said, and what John Harshman and I tried to explain to you (unsuccessfully, it appears - what a surprise) in our comments.

    Let me try again here, trying not to use words with too many syllables: The trouble with Wells' "explanation" is that living things that *don't* use heterochromatin for night vision have lots of it in their genomes, too - animals that are active during the day and sleep at night, and plants also.

    So when Wells says DNA can be functional independent of sequence, he's right in the specific instance he points to, but this won't work as an overall explanation that "junk" is actually functional, since the very same junk is present in living things where it is non-functional.

    This actually supports the point from evolutionary theory that because DNA sequence isn't designed, living things must make do with what the history of mutation has given them, including finding the occasional use for some old bits of evolutionary "junk." Wells isn't nearly the first to point to sequence-independent functions in DNA. There are other well-known examples, such as the natural "antifreeze" of certain cold water fish.

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  15. Presumably Wells is saying that the
    heterochromatin function in nocturnal animals is an example of a "Function Independent of Exact Sequence". And presumably his point is that Functions that are Independent of Exact Sequence can be non-junk.

    Which I take it is a very significant idea as it could apply to a lot of other sequences of DNA that we have not yet deciphered and have incorrectly classified as "junk".

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  16. Anonymous writes:

    And presumably his point is that Functions that are Independent of Exact Sequence can be non-junk.

    That's very acute, Anonymous. Here, I'll make it even more simple for you by cutting out the garbage you have in the middle of your sentence: Anything with a function is by definition not junk.

    Wells has given an example of sequence-independent functional DNA. Notice, though, that since the function Wells uses as an example is so specific (night vision), it doesn't support widespread extension of the principle of sequence-independent functionality across all living things. For instance, Wells' particular example doesn't apply to humans, since we aren't nocturnal. The other examples of sequence-independent function that have been found so far are similar, in that they are very specific functions applicable only in particular species (e.g., fish "antifreeze"), so they really say nothing about non-conserved DNA in other species.

    Might we find sequence-independent functional DNA in humans? Sure. You might even hope to eventually account for a few hundredths of a percent of the human genome that way. And if we did find such functions, I guess that would show we can get non-random functionality out of a random DNA sequence, wouldn't it?

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  17. Jud has posted:
    "Might we find sequence-independent functional DNA in humans? Sure. You might even hope to eventually account for a few hundredths of a percent of the human genome that way."

    Can anyone provide any evidence for the opinion that ONLY a few hundredths of a percent of the human genome might be sequence-independent functional DNA?
    That would be very helpful.
    I am interested in evidence.

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  18. Anonymous writes:

    I am interested in evidence.

    See Matthew 7:16 regarding your claim that you are interested in evidence, while you have steadfastly ignored the reams of evidence Dr. Moran has posted on this very blog over a period of several years, along with many peer-reviewed academic research articles cited by commenters.

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