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Biotech Science

Scientists Discover How DNA Is Folded Within the Nucleus 152

Posted by timothy
from the very-small-laundries dept.
mikael writes "Sciencedaily.com is reporting that scientists have discovered how DNA is folded within the nucleus of a cell such that active genes remain accessible without becoming tangled. The first observation is that genes are actually stored in two locations. The first location acts as a cache where all active genes are kept. The second location is a denser storage area where inactive genes are kept. The second observation is that all genes are stored as fractal globules, which allows genes that are used together to be adjacent to each other when folded, even though they may be far apart when unfolded."
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Scientists Discover How DNA Is Folded Within the Nucleus

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  • How soon before we get folding-paper DNA model artwork?

  • The first observation is that genes are actually stored in two locations. The first location acts as a cache where all active genes are kept. The second location is a denser storage area where inactive genes are kept. The second observation is that all genes are stored as fractal globules, which allows genes that are used together to be adjacent to each other when folded, even though they may be far apart when unfolded.

    Well OBVIOUSLY.
    • by NotQuiteReal (608241) on Thursday October 15, 2009 @06:26PM (#29763501) Journal
      Well OBVIOUSLY

      Yeah now. Seriously, while your answer is a bit flip, I did have that thought as well. All I know about DNA is the usual buzzword stuff - double helix, Crick and Watson, ACGT... etc. I never really thought about what it actually might look like.

      But the diagram showing the tangled mess vs the "fractal" folding evoked a "duh" from me as well.

      The trick is to be the first to prove a non-trivial "duh" fact.
      • Re: (Score:2, Insightful)

        by nomadic (141991)
        I wasn't trying to be flip, I was trying to be sarcastically funny. This wasn't obvious to me at all, and sounded kind of complicated (but then again I'm not a biologist/geneticist/whatever).
      • by treeves (963993)
        I think (IANAMB) that the interesting part is that genes that are "used together" end up adjacent to each other when folded. I don't think that is to be expected.
    • Re: (Score:2, Interesting)

      by Anghwyr (1245932)

      The first observation is that genes are actually stored in two locations.

      This threw me off at first. It read like active genes have a backup stored somewhere in the inactive part. That is not the case =). We're not having and L1/2/3 cache in our genome.

  • Hilbert Curve (Score:3, Interesting)

    by ground.zero.612 (1563557) on Thursday October 15, 2009 @06:18PM (#29763423)
    So, life figured out a form of a Hilbert Curve [wikipedia.org] for storing data? Cool!
  • Obligatory (Score:5, Funny)

    by davidwr (791652) on Thursday October 15, 2009 @06:18PM (#29763431) Homepage Journal

    All your base-pair are belong to us.

    • Re: (Score:3, Insightful)

      by wexsessa (908890)
      "All your base-pair are belong to us" True in some cases, unfortunately, thanks to the USPTO allowing patents on naturally-occurring structures.
      • by Ant P. (974313)

        I wonder how you'd demonstrate prior art for that in court...

        Actually no, I don't want to imagine it.

  • OH YEAH!!!! (Score:4, Funny)

    by Red Flayer (890720) on Thursday October 15, 2009 @06:19PM (#29763437) Journal
    FTA:

    In the past, many scientists had thought that DNA was compressed into a different architecture called an "equilibrium globule," a configuration that is problematic because it can become densely knotted and does not easily open up.

    Key to deciphering the genome's structure was the development of the new Hi-C technique, which permits genome-wide analysis of the proximity of individual genes.

    When questioned about the research, Kool-Aid Man [google.com] could only sob dejectedly as his rival took the glory.

  • So.... (Score:3, Interesting)

    by RabidMoose (746680) on Thursday October 15, 2009 @06:22PM (#29763463) Homepage
    So, what you're telling me, is that DNA naturally defragments itself, in order to be usable even in an archived state?
  • Fascinating (Score:5, Insightful)

    by Taibhsear (1286214) on Thursday October 15, 2009 @06:33PM (#29763575)

    Could all the "junk" DNA that we supposedly don't use maybe have some sort of structural stabilization function? It wouldn't actively code for any proteins but the coding structure itself might allow it to make these shapes and/or allow the globule to move without causing knots in the structure.

    • Re:Fascinating (Score:5, Insightful)

      by wizardforce (1005805) on Thursday October 15, 2009 @06:45PM (#29763699) Journal

      That is possible, non-coding DNA is already known to be a source of raw material for the evolution of functional genes and contains some gene regulatory regions. The concept that it retains other functions outside of direct coding of proteins isn't a new one. Also, few in the biological scientific community really calls "junk DNA" junk DNA any more because of the inaccuracy of doing so.

    • Re:Fascinating (Score:5, Informative)

      by Daniel Dvorkin (106857) * on Thursday October 15, 2009 @07:03PM (#29763873) Homepage Journal

      the "junk" DNA that we supposedly don't use

      This idea seems to have become embedded in the pop-sci mythos nearly as firmly as the "we only use 10% of our brains" thing, and it's equally false. Absolutely everyone working in genetics these days understands that non-coding DNA has multiple biological functions.

      In answer to your question: yes, it's entirely possible. I just really felt the need to get the above out of the way first.

    • What /THE FUCK/ are the scare quotes for? Junk DNA is junk because it's content is useless, if it was there for structural purposes it would consist of the same base-pair repeated over and over. Instead junk DNA is compromised of a healthy dose of post-ad-hoc disabled vestigial genes and garbled ones. Since everything that affects your genome is in a sense part of your genotype it wouldn't be surprising if it is preserved but to suggest this DNA is not made of vestigial genes is, quite frankly, quite sick.

      • Re: (Score:3, Interesting)

        by wizardforce (1005805)

        Except that it isn't all junk. Yes there are vestigial genes and repeats such as Ala however, that does not mean that it serves no structural role. Some repeats especially GGG can distort the DNA coiling structure from the normal B form to other forms that are less useful (eg. Z).

        • Re: (Score:3, Interesting)

          by Requiem18th (742389)

          I don't mean that they are only vestigial and serve no structural purpose.

          But rather that if they were placed there deliberately for structural purpose only it would be obvious and they would be made of vestigial genes.

          They are junk, not "junk".

          • Re: (Score:1, Insightful)

            by Anonymous Coward

            You're acting as if we are really super sure about how they work and what purpose they serve. We have a very good idea of what is likely, but it's not as cut-and-dry as you make it sound.

      • Re: (Score:2, Informative)

        by mollusc (746594)
        Just because a section of DNA doesn't encode a protein doesn't make it useless. A lot of that stuff is transcribed, and I'm pretty sure cells don't transcribe garbled gibberish just for the hell of it.
        • Re: (Score:3, Insightful)

          by tftp (111690)

          Since /. requires a car analogy in every discussion, here is one:

          Engine, transmission and wheels are sufficient to move the car. However not many of us would buy a car that consists only of those three parts.

      • Re:Fascinating (Score:4, Insightful)

        by Daniel Dvorkin (106857) * on Thursday October 15, 2009 @10:06PM (#29765151) Homepage Journal

        What /THE FUCK/ are the scare quotes for? Junk DNA is junk because it's content is useless,

        You have no idea "What /THE FUCK/" you're talking about. Please stop spreading misinformation that even in the 70's, when the term "junk DNA" was coined, people had a vague idea probably wasn't right, and which we've known with certainty for 20+ years isn't true.

        • Re: (Score:2, Interesting)

          by Requiem18th (742389)

          I do, junk DNA, as well as other minerals and enzymes and pretty much anything that floats into the cytoplasm affects the functioning of DNA, they are as much part of your genotype as anything else, as should be expected, because the parts are there and interact, so the interaction must play a role in the expression of the phenotype.

          Two thins are I know are, it wasn't placed there deliberately by some supernatural entity, it does not look even remotely designed, in fact we know exactly what it looks like, v

          • Re: (Score:3, Interesting)

            by Chris Burke (6130)

            I didn't see one scrap of "ID drone" in the OP. I saw someone who showed a surprising amount of open-mindedness and insight for someone carrying around a 30 year old misconception about seemingly unused section of DNA. The "scare quotes" were to imply that what we call "junk" wasn't "junk." Which of course is true even if he didn't know it. It's a tremendous and unjustified leap to go from that to assuming he's say "HAHA GOD DID IT EAT THAT SCIENCE." Do you assume that someone is anti-science any time

            • And none of that is new to me the only news is that I'm running short on temper for creationists, probably caused by reading youtube comments.

    • by d474 (695126) on Thursday October 15, 2009 @07:17PM (#29764031)

      Could all the "junk" DNA that we supposedly don't use maybe have some sort of structural stabilization function?

      That isn't "junk" DNA, that's God's comments inside the code you insensitive heretic!

    • Probably not - it's doing something far more important than that.

      It's already been known for a few years now that the "junk" scales directly with complexity of the organism - unlike number of genes, which does not. It's becoming increasingly apparent that huge numbers of "junk" sections of DNA are actually transcribed to RNA, and play essential roles in regulating what gets made into protein.

      The new hypothesis is that RNA is the computational engine of the cell, allowing it to rapidly process information

      • by Machupo (59568)

        good point -- though the DNA is non-coding, it's structural conformation alone can affect the expression of other factors in the coding DNA.

        • by mollusc (746594)
          It's got nothing to do with the DNA structure: the DNA is transcribed to RNA, usually very small pieces of RNA, and they regulate proteins and other bits of RNA in complex and still poorly understood ways.
    • by v1 (525388)

      considering how things interact with DNA, and how subtle changes in one place can cause unimaginably large changes in other unexpected places ("butterfly effect" of sorts) I believe very little of "junk" DNA is actually "junk", by the conceptual definition. Running over a pebble on the highway may seem irrelevant until you 're not allowed to move the steering wheel. Then see what a different outcome you get ten miles down the road when someone removes the pebble.

    • Re: (Score:3, Interesting)

      by Hurricane78 (562437)

      The idea of "junk DNA" is waaayyy outdated. At least by a decade! It was the old error of arrogance, that led some scientists to believe, that when they could not find a use for it, it must be "junk". Until someone found it to be in heavy use, defining the details of what you become. (There was a very interesting article in the German version of the Scientific American [called "Spektrum der Wissenschaft"] about it, some years ago.)

      It's what also caused people to believe that the spleen (the standing army he

  • how exactly did the DNA get folded in this manner?
    • Re: (Score:3, Informative)

      by MozeeToby (1163751)

      Ok, I'll bite. I'll start by positing that this kind of structure is more efficient or accurate but not 100% necissary to life. An assumption, granted but with a bit of research it should be possible to confirm or deny that hypothesis.

      Given that it isn't necissary and is quite complex primitive life probably didn't have it, but due to the fact that is is more efficient or accurate it became more and more common in the gene pool. You know, the exact same way that any feature evolves.

      • by reverseengineer (580922) on Thursday October 15, 2009 @09:39PM (#29765037)
        I would guess that the development of this sort of fractal packing was a watershed moment in the development of eukaryotic life, but the process itself can be logically seen as an extension of existing processes. Most bacteria, which lack a nucleus, arrange their DNA in a simple circle.

        This has advantages: the entire genome is always accessible for transcription and replication, there aren't telomeres to deal with, and it requires less maintenance. There are disadvantages: if every gene is accessible to the cytoplasm, you have actively keep the 99% you aren't currently using shut off, which is why bacteria use the operon system, and a big circular strand floating around is liable to tie itself in an awful knot. Bacteria have the equipment to fix small topologically issues in their genome, but overall, bacterial genomes are limited in their potential size. Some more complex bacteria have found a partial solution: they draw folds of their circular genome around proteins, to make a single circle more manageable as a group of pinched off loops. So you can see that there's an intermediate stage between "circle" and "our DNA has Hausdorff dimension 3."

        Of course, if you're going to head down the road of DNA folding, you would really benefit from a plan. The beauty of fractals, and a reason they are found so often in the natural world, is that very complex behavior can come from the repeated iteration of very simple rules. Your cells don't need to understand Hilbert curves; all they need is a protein complex that grabs a strand of DNA, then puts a short, specific sequence of folds in it. As that happens along the entire strand, you make a space filling curve that would impress a mathematician.
    • Re: (Score:3, Insightful)

      It's all fractal. All the turtles. All the way down.

      So look at the large scale, and it is clearly evident that the DNA folding is simply a self-similar scaling of the Flying Spaghetti Monster.

    • Anyone with an interest in evolution and what modern studies of evolution are all about really should read this:

      Darwinian Evolution in the light of Genomics [oxfordjournals.org], EV Koonin, Nucleic Acids Research 2009 37(4):1011-1034; doi:10.1093/nar/gkp089

      Does it directly answer your question? No, it does not. However it will give you the framework necessary for understanding answers when they come along. And it is a good overview of where we are in the studies of evolution, what has been refuted in older theories, and what

  • How is DNA folded into the nucleus of a cell without being tangled?

    Very carefully.
  • Great (Score:3, Funny)

    by thewils (463314) on Thursday October 15, 2009 @06:36PM (#29763611) Journal

    Now maybe Apple could apply this structure to my iPod earphones. They're _always_ getting tangled.

    • Re: (Score:3, Informative)

      by troylanes (883822)
      I used to have this problem, too, until I discovered that little white collar on the wire. When not in use, simply slide it all the way up. This prevents the majority of the knotting. Or, just get a pair that occupy 4 dimensional space -- that way it's impossible for them to get tangled up!
      • by thewils (463314)

        The little white collar on 4Gen Shuffles doesn't go all the way up now, the controller gets in the way.

        • by thewils (463314)

          Hey!!!

        • by rsborg (111459)

          The little white collar on 4Gen Shuffles doesn't go all the way up now, the controller gets in the way.

          Which is why they suck. In addition to the rubbery feel which tangles even worse than the iPhone/iPod headphones. I got one of these with my 3GS, and I immediately stole my wife's old pair of 2G headphones.

      • Or, just get a pair that occupy 4 dimensional space -- that way it's impossible for them to get tangled up!

        Ever see a klein bottle? You have no idea the nasty tangles an extra dimension can get you into.

    • Re: (Score:3, Funny)

      by LoverOfJoy (820058)
      I hate it when my schwartz gets tangled.
    • Get yourself some real earphones then. They sound like crap anyway.

  • origami. I hope they can fold my DNA into crane... or a box.
  • My take-away:

    DNA looks like a rubik's cube made out of colored spaghetti.

    Under the old theory, the rubik's spaghetti-sphere looks like it hasn't been solved yet.
    But under the new theory, the puzzle is solved and all the blue shit is next to all the other blue shit, and so on.

    http://web.mit.edu/newsoffice/2009/3d-genome.html [mit.edu]

    • by DynaSoar (714234)

      My take-away:

      DNA looks like a rubik's cube made out of colored spaghetti.

      I was reading all the responses to see if just this one comment got made. It's an excellent starting point to describe the function of the structure.

      Both are designed so components can be far apart at one time, and after a manipulation (or X of them) are adjacent (or have some specific spatial relationship). Both require the manipulations follow a set of rules based on the structure. Most people know how the cube works, with its central rotating axis.

      Imagine first that instead of that amazing little widget,

  • Nice to see 2 familiar names in one article (Grosberg/Mirny)...

  • by angrytuna (599871) on Thursday October 15, 2009 @07:57PM (#29764385)

    I'm confused, here. I'm certainly no biology expert, but I have taken a few courses, one of which the prof seemed to describe exactly how DNA folds. Indeed, it's spelled out in detail on this Wikipedia page on chromatin [wikipedia.org].

    Is this information now obsolete?

    • by Anonymous Coward on Thursday October 15, 2009 @08:34PM (#29764619)

      No it's not, as I understand the paper, the important work was in determining the structure of the folding of heterochromatin. All other theories still apply, we just know more about the folding itself. You can see using electron microscopy that there are discrete locations for heterochromatin and euchromatin inside the nucleus, that theory still apples as well.

      The "beads (histones) on a string (DNA)" architecture is one step above the double helix organizational order, this is also the form of more highly transcribed or "active" DNA (called euchromatin). From there, that string is then wrapped into a much more complex structure which significantly reduces the transcription levels of the mRNAs that this DNA encodes for (called heterochromatin).

      The who field of epigenetics deals with regulating expression of DNA to cause cellular differentiation and changes in cells throughout their lives. One of those ways of regulation is the cell controlling which genes are found in euchromatin and which are found in heterochromatin for certain types of cells at a certain point in their life cycles.

      The post below me about the Hilbert curves is also accurate, thermodynamics is at the heart of all DNA and protein folding.

    • Re: (Score:1, Informative)

      by Anonymous Coward

      the folding referred to in that Wikipedia article is the folding that takes place when cells are about to divide. those X shapes you see under the microscope are two compressed copies of the gene. one copy goes into each cell. then the neat package is unzipped. the folding that is referred to in in this Slashdot post is how it is stored in the cell while it is actively in use.

    • Re: (Score:3, Informative)

      by Anonymous Coward

      No it is more complete.

      This describes genome order at scale larger than the nucleosome. Even the wikipedia article gets a bit vague as you go from the 10nm structures up to the 30nm structures. Notice the change in tone as the section changes from the nucleosome, which is very well described to the "here are a bunch of proposed models" in the next few paragraphs. There really isn't much to tell you where any two genes (separated along the length of a chromosome) should be relative to one-another in space

  • It looks like a Hilbert space filling curve [wikipedia.org] to me.
  • by virtualXTC (609488) on Thursday October 15, 2009 @08:24PM (#29764543) Homepage
    Anyone else wish they could read the actual publication? It's sad considering this is partly taxpayer funded and given the NIH's and Harvard's push toward open access that the authors didn't choose a more accessible journal for such a groundbreaking piece of work.
  • by Dausha (546002)

    The guy who came up with this storage system was pretty damn smart. RAM with a swap drive, parity. Quite intelligent. Not at all random, if I may say so myself.

    • Re:Wow... (Score:5, Informative)

      by Dr. Manhattan (29720) <sorceror171@gmai[ ]om ['l.c' in gap]> on Thursday October 15, 2009 @09:34PM (#29764993) Homepage

      Quite intelligent. Not at all random, if I may say so myself.

      Actually, fractals generate arbitrarily complex structures with very simple rules (e.g. the Mandelbrot Set [wikipedia.org] - take a complex number, square it, add the original number, repeat.) That's pretty much exactly the kind of structure you'd expect an evolutionary process to come up with. If I may say so myself.

    • by Machupo (59568)

      On the surface, it is very easy to attribute the complexity produced by natural selection as a non-random or directed process. Unfortunately, if you look at the number of failures which were required to come up with this arrangement (and the subsequent spread of the most fit type), it's still just as random as any other natural mutation process.

    • You are ignorant about evolution. Anyone who says evolution is "random" doesn't know the first thing about evolution.

      • Re: (Score:1, Flamebait)

        by Dausha (546002)

        And somebody who focuses on my using the word random doesn't understand the first thing about sarcasm. I'm quite aware of evolution; I just don't accept a certain premise upon which it is based. I also don't accept a certain premise about the opposing viewpoint.

        However, I do think the issue itself is petty. It's a fundamentally useless controversy that does nothing to improve the quality of man; but at least reduces us to pointless bickering.

        • Re:Unfortunately (Score:4, Insightful)

          by Nazlfrag (1035012) on Friday October 16, 2009 @12:11AM (#29765709) Journal

          To which premise do you refer? That it is carried out by the passing of genetic information to offspring, or that it is driven by competitively succesful adaption? I'm not sure of any other premises, and while the first seems undeniable (the 'how') the second is more questionable (the 'why'). I'm a bit hesitant that we even have the first clue why, and are barking up the wrong tree entirely. The sheer marvel and scale of the extrodinarily diverse forms that life takes needs a damn good 'why', 'natural selection' just passes the buck to the invisible hand of mother nature. It's not a petty question as to why evolution happens, indeed most of the answers explored so far have given us great insight into all life on Earth. So without invoking omnipotent beings (which evolution doesn't even speak of anyway) or pointlessly bickering could I politely enquire what premise troubles you?

          • sheer marvel and scale

            Both Sanford's "Genetic Entropy" and Behe's "The Edge of Evolution" contain back-of-the-envelope order-of-magnitude musings on "scale" related to the random-mutation-fantasy. David Swift's "Evolution Under the Microscope" stands out for repeatedly marveling over the "folding" issue, including the snip-and-rejoin magic needed to copy a helix. I mean I have repeatedly had the experience of spending tens of minutes unraveling a 50-meter stretch of 11-millimeter Edelrid perlon climbing rope, which is specif

  • by Jah-Wren Ryel (80510) on Thursday October 15, 2009 @11:06PM (#29765441)

    It seems to me that Benoit Mandelbrot's discovery of fractal math is at least as important as Buckminster Fuller's obsession with geodesics. If Fuller got "Bucky Balls," I think fractal globules really ought to be called Benoit Balls.

  • This concept has been the subject of several review articles in the scientific journal Nature - as early as 2007to my knowledge.

  • More information (Score:3, Informative)

    by 93 Escort Wagon (326346) on Friday October 16, 2009 @01:21AM (#29765979)

    While it's not mentioned in the submitted article, I found this explanatory video helpful [youtube.com] in understanding the folding concepts.

  • does the wording of the post sound like a computer geek trying to explain science. So you have this dense storage medium and the bus that runs through it to compile components that ultimately get displayed as proteins.
  • With all these mentions of folding, has this research taken advantage of the Folding@home project? I'm just curious.
    • by physburn (1095481)
      Folding @ home is designed to solve the problem of protein folding. There are 21 different amino acid units that can make up a protein, and each of the amino acid has a very different shape and electrical (or hydrogen-bonding) structure. DNA only has 4 base, is tide to a primary helix form, and so it much much easier to work out how DNA folds. The DNA folding guys wrote the own program and didn't need the huge amount of computers Folding @ home needs.

      ---

      Genetic Engineering [feeddistiller.com] Feed @ Feed Distiller [feeddistiller.com]

  • machina ex Deus :-)

    • by subbyUK (922488)

      what really?

      you think nature is going to get lifted down on a crane and conveniently save the world for us in a lazy script-writer kind of way?

      do you have a newsletter subscription on offer by any chance? :D

  • The first location acts as a cache where all active genes are kept. The second location is a denser storage area where inactive genes are kept.

    "Cache" suggests a rapidly accessible copy, but that's not what's happening.

    It's simply that active genes are accessible while inactive genes are inaccessible. That's not a new insight; that's been known for many years.

    The paper does make valuable contributions, in that it describes the statistics of how genes relate to each other in 3D better than previously known

    • by Chris Burke (6130)

      "Cache" suggests a rapidly accessible copy, but that's not what's happening.

      Only to computer geeks. :)

      Most other uses of 'cache' imply that they are hidden out of the way, saved for a rainy day or guerrilla insurgency. :)

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