Talk:DNA/archive 1
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OK, time to fuss about nomenclature here.
nucleosides are glycosides of bases, whereas
nucleotides are the phosphate esters of nucleosides.
The names for each kind of molecule containing the same type of base are different, ie adenine vs adenosine vs adenosine monophosphate.
- adenine is the base
- adenosine is the nucleoside
- adenosine monophosphate is the nucleotide
I'm not sure where this goes, but it should go in one of the biochemistry-related articles, and it should be borne in mind when writing and editing these articles.
(I have trouble keeping the nomenclature straight myself, having picked up most of my biochemistry along the way, rather than formally. So, this is why I'm maybe a little cranky on the issue ;-) --dja The bases are adenine, guanine, thymine, cytosine, uracil.
The nucleosides are adenosine, guanosine, thymidine, cytidine, and uridine.
I think I made a decent page describing sticky ends and blunt ends and I would like to connect to it from the DNA page. I think it might be good to have a page addressing DNA manipulation techniques, but that is a rather cumbersome name for an article. Can anybody suggest a better name? Recombinant DNA technology? DNA manipulation? Thanks adam
In the DNA page and in the hydrogen bond page emphasis should be given to the fact that the main force responsible for the double helix stability in water is definitively NOT the hydrogen bond! This is a common misunderstanding even in the biochemistry community. Hydrogen bonds are fairly weak in a water environment becuase they readily break up forming new bonds with water molecules. Hydrogen bonds are responsible for the BASE PAIRING. The stability of the base pair and the double-helix shape are instead prevalently determined by hydrophobic effect in the stacking of the base pairs. See "Understanding DNA" by Calladine for review.
- But you could have base stacking in a single helix, so it's hard to see how it could be just the energetic payoff from stacking that glues two strands together. 168...
Answer: The H bond between two organic molecules is a (kinetically?) *weak* bond in a water solution,because water molecules will try to bind more strongly by H bond itself than almost any other molecule. This does not mean it is not important. It is true that base pair in specific ways (WC, Hoogsteen etc.) by mean of hydrogen bonds. Specificity is given by H bonds,indeed. Therefore,when two DNA strands meet in water, it's the high number of complementary H bonds that starts the annealing,probably. If an unsufficient or a geometrically unstable number of H bonds form, no annealing starts. But what makes them remain annealed is mainly (not only,but mainly) hydrophobic effect, as far as I know. The double helix allows the bases to be rigidly stacked, probably lowering entropy cost. Moreover, the helix curve of the phosphate backbone hides the bases from water, better than a single strand would do. At least,that's what I studied in an advanced DNA biochemistry course about 18 months ago...I'll go back to the books and I'll see if I'm right,or it's just my memory falling out.
- So, you seem to be saying that the complementary base-pairing just provides a pathway to a conformation that derives its stability primarily from stacking and from a stearic exclusion of water that creates a high activation energy barrier to de-annealing. But if we are really talking about an equilibrium stability of the double helix and not a kinetically trapped metastable state, I think we can disregard the activation energy barrier posed by the protection of the H-bonds by the backbone. I think the way to think about this is that the bases of two complementary strands could H-bond to water, and yet they choose to bind to another base in the complementary strand. The bases of a free strand could stack without pairing, but perhaps entropy considerations for a strand in solution (where no complementary strands are present) favor a disordered conformation, in which the energy rebate to be derived from stacking goes unexploited. The presense of a complementary strand provides bases an H-bond opportunity other than water, which I suppose changes the entropy considerations and costs, and allows the strands to cash in on the stacking rebate.
- But to what do we credit the annealing of the strands? I wonder if giving credit to the stacking represents a focus on enthalpy and not on entropy. It seems to me that the opportunity for complementary base-pairing merits a lot of credit, because it somehow changes the rules of the entropy game significantly. Otherwise, two complementary strands would do exactly what two non-complementary strands do in solution, and float around as disordered chains. 168... 23
- 54 5 Jul 2003 (UTC)
Hello! I'm the stacking-flamer guy with confused ideas :)! Ok,I went on books a minute (Calladine-Drew "Understanding DNA" and W.Saenger "Principles of Nucleic Acid Structure"). I dont' have them with me now,but here's what I remember now...
Saenger book confirmed me that H bonds between bases are actually *weak* in an aqueous environment
- But you said that the H-bonds between paired bases are shielded from the surrounding water (168)
and can't provide energy for the double helix stability. It talks about DNA annealing almost as 168... says above : "...the complementary base-pairing just provides a pathway to a conformation that derives its stability primarily from stacking and from a stearic exclusion of water that creates a high activation energy barrier to de-annealing."
That's the sense I grasped from the book.
"I think the way to think about this is that the bases of two complementary strands could H-bond to water, and yet they choose to bind to another base in the complementary strand." This seems not to be the (main) case...
- What do you mean by "this"? How could it not be the case in DH DNA? (168)
"The bases of a free strand could stack without pairing, but perhaps entropy considerations for a strand in solution (where no complementary strands are present) favor a disordered conformation, in which the energy rebate to be derived from stacking goes unexploited."
In truth, both books tell me that single stranded DNA/RNA actually stack their bases! Moreover,it seems there are addictional interactions between sequential bases that help stacking.
Bases of a free strand stack,but they pay an entropic cost to do it
- If the base-pairing H bonds hardly count enthalpically and if the bases stack in both ss and DH DNA, then one has to conclude that the only thing that makes DH DNA more stable than ssDNA is an entropy effect due to H bonds, and hence H bonds are more important than stacking. Where's the mistake here? (168)
(and,in fact,that stacking should be quite loose). The DH structure instead provides a sterically relaxed but rigid framework for base stacking, with additional protection from the watery environment. Correct geometry and initial pairing is due to bases H-bonds (and that's emphasized). But the dG stability derives from the stacking,it seems again... ?
- dG stability? I don't know what you are referring to. (168)
I think it's right we're talking of a mostly enthalpic contribution!
Well,I always write these at night and I'm very tired...hope to fix soon some of what I've said.
- Well, thanks for thinking about it. I'll be interested if we can get to the bottom of it. 168... 01:57 11 Jul 2003 (UTC)
Here's all the article says now about the H-bonds' role in double-helical structure:
"In a DNA double helix, two polynucleotide strands come together through complementary pairing of the bases, which occurs by hydrogen bonding....Because pairing causes the nucleotide bases to face the helical axis, the sugar and phosphate groups of the nucleotides run along the outside..."
I don't believe anything anybody has asserted above implies that this is wrong or misleading. That doesn't mean that there isn't anything worthwhile to add to the article regarding stacking. I can think of one place to put it: Right now the pitch (~10 bp per helical turn) is mentioned but unexplained. So I suppose a phrase invoking base stacking might be inserted in that context as a bit of explanation, which would at the same time point to how strongly a role it plays in the double helix. 168...
Actually, I just went in and inserted something like that. 168... 00:21 6 Jul 2003 (UTC)
The historical account of the discovery of the structure of DNA given in this article appears to contradict Watson's The Double Helix. In that account, Watson and Crick's failed model (with the backbone inside), predated their knowledge of the B-form discovered by Rosalind Franklin. Even when they had secured access to the B-form diffraction photograph, they still exhaustively explored backbone inside models before experimenting with backbone outside ones. This discrepancy needs resolving. -- Alan Peakall 15:08 Jan 6, 2003 (UTC)
Hmmm. Sounds perfectly plausible, if not familiar. In telling/editing the history, I have been following the lead set by a previous contributor to this page, and I don't have the Double Helix/8th Day of Creation/etc on my bookshelf. Can anybody propose a narration of what Franklin's presented and what model W&C went home to build in response? If Franklin did perceive that the phosphates are outside, was it on the basis of the data that she showed at the alleged presentation that this article cites, did she present this implication of her data explicitly, and if she did, why would W&C have dismissed or forgotten this finding when they went home to build a model that would agree with her data? Perhaps the point of the original author of this history was to credit Franklin with being the first to realize the phosphates were outside, but he or she didn't know exactly how to put it, or put it so vaguely that under editing the text wandered from the truth.168... 20:09 4 Jun 2003 (UTC)
[User:MikeS] Very interesting, thanks. I do have a question, I hope has an answer.
First, some have written about "genetic diseases" perhaps based on DNA strand segments being identical between parent and offspring, in "functionally-similar" locations along the DNA, with the child having, or being "pre-disposed" to, the illness of the parent. I understand there is an island off Venezuela in which all suffer from the same eye disease and the common DNA segment has been identified but, no cure was known, (c. 1998?).
Second, the fight against the West Nile Fever now depends on the fact that the DNA of infected chickens is altered when they are infected, even though they show no syptoms of the disease.
So, which is true? Is the gene altered by the disease or is the disease the consequence of a DNA "genetic disease" gene strand segment. Seems like a chicken-egg question, but it is, most definitely, not. Could the people in the island be infected by the same virus and their DNA show the same evidence as the West Nile Fever infected chickens? Health Insurance companies and buyers are placing their bet on the answer. 24-Jul-03[User:MikeS]
I'm a little confused by your question and don't know the island or disease you're talking about (there's Oliver Sack's book "The Island of the Color Blind," but that island in question isn't off Venezula, I don't think). But I think I might be able to help a little. There was a Nobel Prize awarded to the people who discovered that cancer may come either from the DNA in our chromosomes or from viruses. On the one hand, a virus may carry around defective copy of an oncogene, so that an infected cell makes a cancer-causing protein in reproducing the virus. On the other hand, the chromosomal oncogene in one of a person's cells may go defective by itself, through mutation. So here's a case of a disease that can be one or the other. Another thing about certain types of viruses is that they insert their own DNA into the chromosomes of their host cells. The insertion can disrupt host genes at the sites of insertion. 168... 18:18 24 Jul 2003 (UTC)
[User:MikeS]The answer is clear. It could be either and if we focus on the molecular biology, much research work will lead to a new highly profitable drug. If the focus is to find the mosquito, or whatever caused the infection, well, you know. However, to be explicit. If we agree, and the evidence shows, that some illnesses alter DNA; and, as evidence also shows, the DNA has a marker that identify those that were infected, Then, like the previous pointed out, there is no way to know if the DNA segment was caused by an illness or inherited. In either case, Insurance companies may save money by DNA examination. Therefore, it should be illegal?
To be more explicit. If the focus is on "curing" by DNA modification, and this has been tried with promising and deadly results, then it appears to ignore immediate causes, you know? Like larvae in drinking water, mosquito bites, pollutants and pollen in the air, etc. That is, we will ignore the cause and deal with symptoms. Sounds familiar? --[User:MikeS]