Scientists Discover How DNA Is Folded Within the Nucleus 152
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."
Re:Great (Score:3, Informative)
Re:Fascinating (Score:5, Informative)
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.
Re:An obvious question arises... (Score:3, Informative)
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.
"Junk" = regulatory RNA (Score:2, Informative)
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 and react appropriately, and the non-protein-coding "junk" sections are what it uses to do this.
There's a guy called John Mattick [uq.edu.au] from the University of Queensland who has done a lot of really exciting work in this area, and gives a fantastic talk on the subject - here's an abstract for a version of it. [cam.ac.uk] Sample quote:
the extent of non-protein-coding DNA increases with increasing complexity, reaching 98.8% in humans, suggesting that much of the information required to program development may reside in these sequences. Moreover it is now evident the majority of the mammalian genome is transcribed, mainly into non-protein-coding RNAs (ncRNAs), and that there are tens if not hundreds of thousands of long and short RNAs in mammals that show specific expression patterns and subcellular locations. Our studies indicate that these RNAs form a massive hidden network of regulatory information that regulates epigenetic processes and directs the precise patterns of gene expression during growth and development.
Using the argument that cells are RNA machines, there is most likely no junk whatsoever in the human genome.
Re:Fascinating (Score:2, Informative)
Re:Fascinating (Score:3, Informative)
Re:What about beads on a string? (Score:5, Informative)
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:Wow... (Score:5, Informative)
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.
Re:An obvious question arises... (Score:5, Informative)
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:What about beads on a string? (Score:1, Informative)
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:What about beads on a string? (Score:3, Informative)
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.
This study shows that DNA is packed into the nucleus in an ordered fashion, by direct observation of all the spatially close bits. These end up not being random at all. Instead they are consistent with a fractal globule. I'd never heard of these before, but they have some interesting properties with regard to tangling. Which is probably the best thing about this for me, polymers of this length should tend to get horribly tangled, which would be bad, given that the cell has to split them up every time it divides.
Overall, very neat, really hard work.
-sk
Obligatory Evolution README (Score:3, Informative)
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 directions future studies will be taking.
More information (Score:3, Informative)
While it's not mentioned in the submitted article, I found this explanatory video helpful [youtube.com] in understanding the folding concepts.