Exploring the Macro Topology of DNA

[Skaffen]

Hi,
I'm more conversant with Physics than Biology, and I think this question may actually apply more to the computer sciences so pls bear with me -

DNA is represented as a 'strand', and is analogous with a 'line' of code. Turing envisioned the computing process as two 'infinite' strings, however we employ a stop process to resolve our computations.

If one long strand is curled into a spiral it could in effect be a series of potential calculations between each layer of the spiral?

So, is DNA a strand in situ? Or does it potentially self reference like a spiral...or other?

What is DNA's macro topology when its doing it's thing?

 

[jleach]

DNA and protein structures are described at different levels, because the 3-D structure significantly impacts the activity or message. The sequence is merely the primary structure and is usually considered to be the most telling bit of information. However, gene regulation and translation can be a lot more complex than merely looking at the primary sequence. A single primary sequence can code for more than one protein. Proteins bound to the DNA help to fold and unfold segments of the strand. This is how genes are usually turned on or off. I can't say that I know if this happens in DNA, but for proteins, the folded structure can result in a surface sequence, which is recognized by an antibody. When the protein is unfolded, the recognized surface sequence is no longer there.

Without straying too far, I've always hated overly generalized statements like "our genome is 99% identical to that of chimps". This statement has been floating around for a long time since before the human genome project started. Now, I believe in evolution, so I'm not trying to create a debate against our simularity to chimps. But, I am saying that such a statement is irresponsible and premature. It's like saying that all houses are identical if they use the same type and proportions of nails and boards. Everything in the natural world is composed of about 99 natural elements, and carbon is the main element of life. Is this sufficient criteria to say that I'm closely related to a lump of coal?

 

[Skaffen]

When the protein is unfolded, the recognized surface sequence is no longer there.

Thank you jleach. It is this aspect of the diversity of a strand being reconfigured into a different geometry's that fuels my question. :!)

I have illustrated with a spiral as it seems to me that within any given environment the strand, or rather relationship of segments on the strand, has maximum potential (ie changing self reference) as a spiral (2D), yet remains stable.

I believe you have confirmed this aspect is a known biological system with regards to proteins.

As I mentioned previously I am more read on Physics and it was from consideration of Relativity which lead me to viewing DNA as a boundary between environment and 'host'. Evolution (notably Diversity) would suffer from a single interpretation therefore the coding system cannot be passive but relative and responsive beyond just the environmental dictations.

Mostly I find DNA being described as a sequence from end to end, I have never heard it discussed as a varying geometry/surfaces. If proteins are transformers then I believe DNA must also have this aspect.

Sources/opinions very welcome, perhaps Biology has something for me after all...woot!

 

[jleach]

It is well known that your genome can respond to the environment, but these responses are not believed to result in an inheritable trait. If you exercise, you can become a body builder, but this won't make your children any stronger. Environmental stress can trigger the activation or deactivation of genes, but your genome remains the same. However, I have a suspicion that there may be a way to pass on some characteristics created by environmental stress. I don't normally share this idea, because it would make me a herotic, and I still need to convince myself, before I start talking about it. Touching close upon this idea, I think that there is a NOVA series that talks about how environmental stress on the grandfather triggers a response observed in grandchildren. Rates of gene recombination are directly related to the position of the gene and how tightly wrapped that segment of the DNA is contained. I suspect that environmental pressures which influence the folding and unfolding of genes may make it possible to change the probability of passing on certain traits.

 

[Monique]

No-one has mentioned it yet, but DNA is wrapped around histones and it exists in an euchromatin (open/active) and heterochromatin (closed/repressed) state. These states were identified based on histological examination, currently much more is known about histone modifications and packing.

An upcoming field is how DNA is packaged into the nucleus. It is starting to become clear that DNA associates with the nuclear envelope, where it is inactive. A gene that is activated will move away from the nuclear envelope. Researchers are now trying to understand what the importance of this process is and how the process is regulated.

 

[Skaffen]

An upcoming field is how DNA is packaged into the nucleus. It is starting to become clear that DNA associates with the nuclear envelope, where it is inactive. A gene that is activated will move away from the nuclear envelope. Researchers are now trying to understand what the importance of this process is and how the process is regulated.

Thank you Monique.
Feels like you have kicked me in the head wearing a size 10 pair of knowledge boots

I need to look at this idea of nuclear envelope, I'll wiki it, although if you have link to a source I would be in your debt...even more.

It seems the mainstream depiction of a 'strand' is misleading, although if the field of research is only upcoming with respect to 'packaged geometry' then it is only transitory.

A single sequence (IMO) could not justify the complexity of DNA's contribution, from an information point of view. However if you have a 3D or even 2D 'grid' the potential is magnified. {Analogous to a word search).

As the structure must have the ability to generate 'words' it must have spaces (environment/nucleus) between the 'letters' and preconfigured rules which determine where the words are. (eg. Diagonal, left-right, up-down, down-up).

A stacked spiral seems the natural/conservative guess to me, as it offers most degrees of freedom without incurring additional mechanisms at this stage. It would also play like a record through simple self rotation...polish those size 10's.

Away to learn about histones and euchromatin!

 

[Andy Resnick]

Since you asked about DNA acting on itself, it's worth noting that RNA can autocatalyze to build up larger structures:

http://www.nature.com/nchembio/journal/v4/n11/full/nchembio1108-654.html

 

[Skaffen]

Cheers Andy

Am I right in thinking that RNA is effectively the secondary messenger (runner)? - It would suggest then that DNA is more like a Library sending out books, so the RNA (book) would define the position of archival but not method (Alphabetical, Subject matter, Frequency of Issue etc).

Back to Geometry where my tiny little mind can grasp the obvious :) - A double helix is like a corkscrew (bear with me I appreciate the analogies are tiresome). A corkscrew through rotation effects it's environment by separating the medium it is in into 2 new configurations. Thus nucleic behaviour (rotation as a suggestion) would alter its environment and allow it to evolve more diverse combinations through time.

DNA! Man! I'm probably best back to the physics...I know the playing field better. Biology is maybe to far up the tree for a monkey like me.

edit: got a notion of the histones as a support structure for the DNA, if I may suggest DNA has an inside and an outside that it must process instruction through so perhaps the corkscrew analogy has some merit?

 

[madcat8000]

Histones have many effects. In one position they are simply in the way of the DNA being processed, and sometimes they make direct temporay effects that can regulate its expression positively and negatively. The shape of the DNA molecule itself implys only one function though (to me), protection of the information. The less stable, more reactive information is guarded on the inside while the unreactive outside protects it. By coiling on itself the outside dose even more to protect the information. And yes with exceptions you are quite right that RNA is merely a photocopy of the DNA book. But sometimes that photocopy can fold itself into a tool, that's the idea of the RNA world, that at one time RNA might have been the information, information carrier, and end tool for biochemistry with no help from DNA or maybe even protines. In some rare cases Ribo-zymes are still better at their jobs than the decending protines, and some viruses are RNA only.

 

[Skaffen]

Histones have many effects. In one position they are simply in the way of the DNA being processed, and sometimes they make direct temporay effects that can regulate its expression positively and negatively. The shape of the DNA molecule itself implys only one function though (to me), protection of the information. The less stable, more reactive information is guarded on the inside while the unreactive outside protects it. By coiling on itself the outside dose even more to protect the information. And yes with exceptions you are quite right that RNA is merely a photocopy of the DNA book. But sometimes that photocopy can fold itself into a tool, that's the idea of the RNA world, that at one time RNA might have been the information, information carrier, and end tool for biochemistry with no help from DNA or maybe even protines...and some viruses are RNA only.

Hey MCat,

Just been trying to get my head around the various layers - it seems folding and coiling is a considerably well understood facet of Genetic interplay - Initially I thought DNA was just reproducing itself in a more isolated manner with a background of protein soup, then I thought it must act as boundary (which it does), however the emphasis on it being kinda 'independent' was wrong as it has Lego for all occasions and there are well over a dozen other boundaries refining and prepping the materials for it...in the same way our stomach bacteria breaks down our food yet is separate from us regarding strict genetics.

I think nature has created large scale creatures incrementally built from autonomous yet minuscule bacteria and viruses (following the genetic jigsaw) - it ensures diversity (even in the individual), and allows short term 'bolt-on' adaptability if you are 'consuming' potential allies on a regular basis (see below). It may also prevent a single species from destroying diversity by dominating at great expense as there will always be a potential inner enemy.

http://izismile.com/2009/09/09/the_...parasite_living_in_a_fishs_mouth_18_pics.html

 

[madcat8000]

I think you are on the right track in many ways at least in your own head. Wish I could understand mathematics to the degree you do. I am very sure every facet of biology could benefit from more such perspectives. But I am just a dumb ape that's really good at putting together complicated structers together in my head. I do hope you continue your interest in biology, hybrid vigor for the win!

 

[Andy Resnick]

Back to Geometry where my tiny little mind can grasp the obvious :) - A double helix is like a corkscrew (bear with me I appreciate the analogies are tiresome). A corkscrew through rotation effects it's environment by separating the medium it is in into 2 new configurations. Thus nucleic behaviour (rotation as a suggestion) would alter its environment and allow it to evolve more diverse combinations through time.
?

This is the best pic I could find:

http://employees.csbsju.edu/hjakubowski/classes/ch331/dna/chromosome.gif

As you can see, the geometry of packaged DNA is fairly complex. Monique's comments regarding how specific genes are accessed are very salient.

 

[Monique]

This is the best pic I could find:

http://employees.csbsju.edu/hjakubowski/classes/ch331/dna/chromosome.gif

As you can see, the geometry of packaged DNA is fairly complex. Monique's comments regarding how specific genes are accessed are very salient.

Do note that the picture depicts a cell that has started the process of mitosis: it's in prophase. The geometry as depicted in the top part is not how interphase DNA normally looks. The bottom part show how DNA is wound around histones, but the picture is pretty basic.

Here's a picture of how the DNA is wound around histones: http://www.mun.ca/biology/scarr/Histone_Protein_Structure.html or just search for nucleosome. These are only local DNA configuration, but you should understand that DNA can also interact over long distances or even between different chromosomes: they can form loops and influence expression levels. Again, that is a new field and people are trying to understand how that works.

 

[mishrashubham]

This is something that I would like to quote from nature.com (http://www.nature.com/horizon/proteinfolding/background/importance.html) which is maitained by the Nature Publishing Group

The sequence of amino acids in a protein defines its primary structure. The blueprint for each amino acid is laid down by sets of three letters known as base triplets that are found in the coding regions of genes. These base triplets are recognized by ribosomes, the protein building sites of the cell, which create and successively join the amino acids together. This is a remarkably quick process: a protein of 300 amino acids will be made in little more than a minute.

The result is a linear chain of amino acids, but this only becomes a functional protein when it folds into its three-dimensional (tertiary structure) form. This occurs through an intermediate form, known as secondary structure, the most common of which are the rod-like a-helix and the plate-like b-pleated sheet (Fig. 3). These secondary structures are formed by a small number of amino acids that are close together, which then, in turn, interact, fold and coil to produce the tertiary structure that contains its functional regions (called domains).

Although it is possible to deduce the primary structure of a protein from a genes sequence, its tertiary structure cannot be determined (although it should become possible to make predictions when more tertiary sequences are submitted to databases). It can only be determined by complex experimental analyses and, at present, this information is only known for about 10% of proteins. It is therefore not yet known how an amino-acid chain folds into its tertiary structure in the short time scale (fractions of a second) that occurs in the cell. So, there is a huge gap in our knowledge of how we move from protein sequence to function in living organisms: the line of sight from the genetic blueprint for a protein to its biological function is blocked by the impenetrable jungle of protein folding, and some researchers believe that clearing this jungle is the most important task in biochemistry at present.

 

[Skaffen]

Thanks Mishrashubham - great article :)

It seems that folding to the most conservative geometry is a facet driving many levels of genetic translations. Although the magnitude of combinations is almost infinite each 'fold' should in some sense represent a 'prime', analogous to number theory, IMO. These 'prime' sequences, being irreducible in this context and conferring geometry must be defined and thus bounded.

Interestingly, 'Ulam's Spiral' appears to offer a potential mathematical framework which puts primes within proximity of each other geometrically. - Is there an established train of thought? I appreciate I may be repeating what is already known in academic circles.

 

[Skaffen]

Done a bit more reading over the weekend and would like to apply the Ulam spiral to an actual dna sequence. Tried to Google an example but can't find one. Preferably the initial few hundred base pairs of a mapped genome. If anyone can point me in the right direction it would be greatly appreciated.

I don't know exactly what kind of pattern I am looking for but in essence I believe there should be a trigger delineating 'words' (RNA) (analogous to a space between words in a sentence). Rather than a single spiral I consider a series of spirals and it is between these I hope to find a common marker indicating a change in orientation. The Fibonacci sequence is evident in biological systems, perhaps Ulam's spiral has at a different scale?

 

[madcat8000]

Wouldnt it be interesting if you were to find that the splintered genes of Eukaryotes followed this pattern.

 

[Monique]

Done a bit more reading over the weekend and would like to apply the Ulam spiral to an actual dna sequence. Tried to Google an example but can't find one. Preferably the initial few hundred base pairs of a mapped genome. If anyone can point me in the right direction it would be greatly appreciated.

I don't know exactly what kind of pattern I am looking for but in essence I believe there should be a trigger delineating 'words' (RNA) (analogous to a space between words in a sentence). Rather than a single spiral I consider a series of spirals and it is between these I hope to find a common marker indicating a change in orientation. The Fibonacci sequence is evident in biological systems, perhaps Ulam's spiral has at a different scale?

What are you trying to do here? People have already developed computer programs that predict the start and end of genes. With DNA alone you cannot predict the geometry, there are many proteins required to bind to a promoter of a gene that allow transcription to start. These proteins play a large role in determining the geometry of the DNA sequence.

 

[Skaffen]

Hi Monique,
I appreciate there are models which predict position of the genes - I hope to apply a conserved geometry (sequence of spirals) to the raw sequence and cross reference current predictions with any patterns in an 'idealised' secondary structure(s). The 5'3' characteristics between the prime and lagging strand could infer a new correlation between base pairs which may be revealed via geometry.

I just want to play around with a sequence and hope to find more questions that I can use to deeper my understanding of the information aspect of dna. It's probably been done as you say, however I would like to develop it through my own intuition.

Rgds, Skaff.

 

[Monique]

Have you ever taken a basic biology course that covers the DNA-RNA-protein paradigm? Do you understand the molecular structure of DNA and the primary to tertiary structures that describe the molecule? The reason I ask is that you seem to be missing a lot of information.

 

[Skaffen]

I understand that all processes are reducible and consequently have begun at the beginning of the complexity. I appreciate many have done this before me (and better), however knowledge is a poor substitute to understanding and it is in furthering the latter that I make use of my time.

I understand DNA as a repository of information, I also understand that secondary/tertiary structure is created through geometric translation. I know of many interactions that are driven from this, but also know there is far more that I know nothing of.

I haven't gotten to considering RNA-Protein yet as I don't understand how to get from DNA-RNA (might never). I know you know, as will many others, and that knowledge will frame my pursuit of understanding.

This forum is dominated by an elitist mindset which denigrates individual thought and serves as a 'paste' environment for established esoteric jargon that often seems deliberately obscure and dogmatic. Feynman would love it.
Bye.

 

[Monique]

Knowledge comes from asking the right questions, not from thinking you can figure it all out by yourself. I don't think you appreciate what others have done before you, since it does not appear that you've researched the subject.

I can suggest this http://books.google.com/books?id=iG...AEwAA#v=onepage&q=dna ta gc distance&f=false" to you, please take special note of the paragraph "Watson-Crick base pairs have virtually identical dimensions". I assume you know what Watson and Crick did (or rather, Rosalind Franklin). From that information how do you suggest that you can model an alternative structure?

This forum is dominated by an elitist mindset which denigrates individual thought and serves as a 'paste' environment for established esoteric jargon that often seems deliberately obscure and dogmatic. Feynman would love it.

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