Talk:DNA: Difference between revisions

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imported>Chris Day
(do we want to salvage any of this old history section?)
imported>Chris Day
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==Do we want to axe the istory section?==
==Do we want to axe the history section?==
In the following series of edits Nancy axed the history section.[http://en.citizendium.org/wiki?title=DNA&diff=100119207&oldid=100119126]  My guess is that many readers come to DNA from a historical perspective so might like to see that context presented, even if very briefly. I have cut and paste the section into this talk page here:
In the following series of edits Nancy axed the history section.[http://en.citizendium.org/wiki?title=DNA&diff=100119207&oldid=100119126]  My guess is that many readers come to DNA from a historical perspective so might like to see that context presented, even if very briefly. I have cut and paste the section into this talk page here:
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Revision as of 01:03, 3 July 2007


Article Checklist for "DNA"
Workgroup category or categories Chemistry Workgroup, Biology Workgroup [Categories OK]
Article status Developed article: complete or nearly so
Underlinked article? No
Basic cleanup done? Yes
Checklist last edited by --Aleksander Stos 12:02, 27 June 2007 (CDT)

To learn how to fill out this checklist, please see CZ:The Article Checklist.





Approval Area

I placed the ToApprove template for this article and given two weeks per Biology editor Nancy Sculerati. Matt Innis (Talk) 15:38, 7 June 2007 (CDT)

Copyright violation?

This looks like just a rip of a Wikipedia article... can someone fix it? Shanya Almafeta 15:28, 11 February 2007 (CST)

We should all edit it. Before the unfork, we had all the WP articles, and as they became different we made them CZ live. I see your concern, but it is legitimate to import articles and then work on them. Nancy Sculerati MD 15:33, 11 February 2007 (CST)


Proposition:

This article is far too big.

Lets identify 1. the correct sections for a coherent comprehesive introduction to understanding the key biological roles of DNA

2. Packages that form the nuclueus of other vital biology topics.

I'm talkin' RADICAL SURGERY HERE.

Che?

David Tribe 01:33, 12 February 2007 (CST)

Here is the current content:

1 Physical and chemical properties
1.1 Base pairing
1.2 Sense and antisense
1.3 Supercoiling
1.4 Alternative double-helical structures
1.5 Quadruplex structures
2 Chemical modifications
2.1 Regulatory base modifications
2.2 DNA damage
3 Overview of biological functions
3.1 Transcription and translation
3.2 Replication
4 Genes and genomes
5 Interactions with proteins
5.1 DNA-binding proteins
5.2 DNA-modifying enzymes
5.2.1 Nucleases and ligases
5.2.2 Topoisomerases and helicases
5.2.3 Polymerases
6 Genetic recombination
7 Uses in technology
7.1 Forensics
7.2 Bioinformatics
7.3 DNA and computation
7.4 History and anthropology
8 History

I have bolded what seem to be fundamental and should be kept at some level for a primer article. Feel free to add or subrtract from this initial cut. Chris Day (Talk) 01:44, 12 February 2007 (CST)

I disagree with both of you and really like the long detailed article. You just hit cntrl+f or apple key+f and you can find whatever you want in the article. Why not make a simple version as a separate article? -Tom Kelly (Talk) 01:57, 12 February 2007 (CST)
I think what David is suggesting is a primer version, although I don't what to speak for him too much. In my opinion the two could definitely co-exhist. We can have our cake and eat it. Chris Day (Talk) 02:02, 12 February 2007 (CST)
Im not wanting to be dogmatic and don't want to throw anything out just (thinking of) putting some of it elsewhere. It might work if we concentrate on developing all the essentils first but keep it all in one place,

but my point remains that many of these sections are part of important bifgeer stories we also need to write Eg

3.1 Transcription and translation
6 Genetic recombination
7.1 Forensics
7.2 Bioinformatics
7.3 DNA and computation
7.4 History and anthropology'

all these are specialist fields each with a huge story to tell that cannot be done justly here. Why not get those jobs started>, and also do them well


Some comments TEMPORARILY transferred to Talk:Primer on DNA David Tribe 17:23, 12 February 2007 (CST)

But a few hours later RETURNED

Separate Primer rejected

Then returned after discussion with Larry: Still want the lead in developed better and a beeter layout that has a lot of thought about what content is appropriate 22:02, 12 February 2007 (CST)~

DNA essentials?

Top priority is to find a way to create an article that novices will learn a lot of important stuff easily.

Lets keep talking to discover whats the best structure that achieves this and whether for instance thats with a primer plus a big article.

In important topics like DNA a separate primer maybe a good idea. Maybe we can start a tradition of primers, maybe not. Larry might have some argument that its bad.

One way is to have a little link at the top saying DNA primer for those who need the simplest essentials. Unfortunately DNA primer by itself has a special meaning so we could call it DNA for beginners. waadya think? David Tribe 03:47, 12 February 2007 (CST)

Again I put it as a proposition., not a firm judgment and I appreciate the courteous contrary opinion. Maybe we should wait for some others to say something? David Tribe 03:56, 12 February 2007 (CST)

The following analogies are well intentioned but I judge them to be deeply misleading and factually incorrect. DNA is NOT , emphatically NOT, analogous to an operating system. Its not used like a blueprint either- there is no overall physical correspondence between DNA and cellular morphology:

"All cellular organisms contain DNA. DNA, along with other organic molecules, provides a sort of operating system for an organism. It's also compared to a blueprint, since it contains the instructions to construct other components of the cell, namely proteins and RNA molecules. " David Tribe 14:20, 12 February 2007 (CST)

Anaologies for the function of DNA are very difficult to get right across all levels. I agree the blueprint and operating systems are inaccurate and probably not that useful. With repect to hierarchy the best I have seen is a library (the nucleus) with the community as a cell; including police, builders and hospitals. Within the library the shelves were the chromosomes, the books the genes the words the code, the letters the bases. In this usages the DNA is much more than a blue print. The operating system does not work well since it represents information in action, more like the whole cell than just the DNA. Anyway, since no really good analogies are out there it might be best to stick to reality. Chris Day (Talk) 14:28, 12 February 2007 (CST)
Just had a long and fruitful telephone conversation with Rob Tito about analogies (and more importantly COFFEE heck Ive used so many languages for this essential chemical of life that Ive forgotten the english spelling for caffe'). We explored a version of analogy with operating system and Zipfiles that might work. It may well return to the text in a form thats satisfactory David Tribe 15:29, 12 February 2007 (CST)
I just looked to see what is on the web and there are quite a few anaologies out there. Here is one for an operating system where the nucleus of the cell is the kernel of the operating system and the DNA is represented by the source code. This is simlar to my idea above where the DNA represents a subset of the operating system. Chris Day (Talk) 15:38, 12 February 2007 (CST)

Here is another nice one. Chris Day (Talk) 15:50, 12 February 2007 (CST)

Matrix of biology and computer science.
Biology Computer science
1. Digital alphabet consists of bases A, C, T, G 1. Digital alphabet consists of 0, 1
2. Codons consist of three bases 2. Computer bits form bytes
3. Genes consist of codons 3. Files consist of bytes
4. Promoters indicate gene locations 4. File-allocation table indicates file locations
5. DNA information is transcribed into hnRNA and processed into mRNA 5. Disc information is transcribed into RAM
6. mRNA information is translated into proteins 6. RAM information is translated onto a screen or paper
7. Genes may be organized into operons or groups with similar promoters 7. Files are organized into folders
8. "Old" genes are not destroyed; their promoters become nonfunctional 8. "Old" files are not destroyed; references to their location are deleted
9. Entire chromosomes are replicated 9. Entire discs can be copied
10. Genes can diversify into a family of genes through duplication 10. Files can be modified into a family of related files
11. DNA from a donor can be inserted into host chromosomes 11. Digital information can be inserted into files
12. Biological viruses disrupt genetic instructions 12. Computer viruses disrupt software instructions
13. Natural selection modifies the genetic basis of organism design 13. Natural selection procedures modify the software that specifies a machine design
14. A successful genotype in a natural population outcompetes others 14. A successful website attracts more "hits" than others


I have decided to run with Primer on DNA. DNA primer is unfortunate, and PLoS sets the example. Ill do a link in the article and start this again and Tom will rest happy. 17:00, 12 February 2007 (CST)

LOL, I wasn't loosing sleep over it. I just think we could have one article for the nonscientific (meaning for those who have no interest or training in hard science) that is the main article that comes up when you type in DNA. Then you could write another that is really complex, putting big names in it etc etc. I would have the primer come up when DNA is typed in. However I would not call it a Primer... would you? seeing how we use primers with PCR, etc... right? -Tom Kelly (Talk) 21:17, 12 February 2007 (CST)

Should we tag with Health Sciences Workgroup category?

what do you think? -Tom Kelly (Talk) 16:13, 11 March 2007 (CDT)

No harm, I guess, although it seems a little too basic to be in that category. Mutation, on the other hand, should definitely be in the health science workgroup. Chris Day (Talk) 10:08, 12 March 2007 (CDT)

Unprotecting

Doesn't seem to be a reason to have this protected. --Mike Johnson 20:04, 25 March 2007 (CDT)

Images - licensing

Most of the images in this article unfortunately aren't sourced (i.e. no links to where they came from and what license they're available under), so I've gotta delete em. --Mike Johnson 16:08, 26 March 2007 (CDT)

In accordance with the Big Cleanup guidelines, I'm removing the broken image links. Petréa Mitchell 22:00, 28 March 2007 (CDT)

Approval

This key article lacks for nothing but our attention. I am nominating it for approval with a relatively long lead time, I will spend at least 30 minutes every day until then, and I'm hoping that the DNA scientists out there will do the same- maybe in aggregate. Nancy Sculerati 14:58, 7 June 2007 (CDT)

sorry been out of the loop. Will certainly try and do some editing here too. Chris Day (talk) 15:52, 7 June 2007 (CDT)

Thank heavens! Somebody who really knows what he's doing! :-) Nancy Sculerati 16:03, 7 June 2007 (CDT)

For further informations see:

I suggest removing these directives as they are really designed for WP. In some cases, it would be preferrable to leave them and start the article that they refer to here, I think. Nancy Sculerati 09:05, 8 June 2007 (CDT)

reversion

All due respect, the last two edits are wrong, each strand gets a complimentary strand and the result is two identical double helixes. Please do not copyedit for language unless you are absolutely sure of the science. We need more new content and would love to see some new articles - especially from scratch. Nancy Sculerati 18:24, 9 June 2007 (CDT)

I am one of those novices wishing to learn more about DNA. I found this article restates what it took me years to figure out bit bit. Eventually I was surprised to find out that DNA isn't duplicated, it is the complementary that is duplicated. Kornberg explains on page 13 DNA Replication that the entire DNA process is complementary, calling this the most important feature of the duplex model. Thomas Mandel 19:12, 9 June 2007 (CDT)
The term for this concept is semi-conservative replication. Yes indeed complementarity is a key feature of both RNA and DNA. The question is : is it communicated well at CZ. The intent of my earlier revision was to display this and other things clearly. I'm not quite sure why that section was eliminated. Its not a problem to me but some further discussion of simplicity of communication is worth having. My main issue with the WP version was one couldnt see the wood for the trees.David Tribe 20:42, 10 June 2007 (CDT)

Thomas, we are trying to get this article into shape for approval. It is now nominated for approval with a long lead, because it needs expert attention. It is not the place, if you wish to help the wiki, to experiment with edits as a novice who wants to learn abut the subject. There are so many articles that are only stubs and so many subjects that are not written about here, perhaps you would help us out and work on them? If you would like to help this article, if there are sentences that don't make sense to you, as a novice, or areas that you wish were here, that yo wanted to know about but are not, if you would explain these on the talk page, we can address them and that will help make it a better article. Nancy Sculerati 19:20, 9 June 2007 (CDT)

I have authored the new article Systems Theory, don't know how I happened to read your article, notice that in systems theory the complementary plays a leading role. I wish that the complementary aspect was made explicite. Kornberg writes "The most important feature of the duplex model for DNA structure is the introduction of the concept of Complementarity. ...Complementarity has come to explain transcription and translation and thus the entire sequence of events in the expression of genetic functions."

Indeed, complementarity plays the leading role in every aspect of DNA, assuming, that is, if the concept is broadened to include complementary structures.

Thomas Mandel 20:01, 9 June 2007 (CDT)

Proposed Sentence Cut

Re: sentence: A considerable number of DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, have overlapping genes which may both occur in the same direction, on the same strand (parallel) or in opposite directions, on opposite strands (antiparallel), thus bluring the distinction made above between sense and antisense strands.

I would argue that overlap does not blur the distinction between sense and antisense, since the sense and antisense are only applicable to a particular gene - the antisense strand for one gene can be the sense strand for another gene and this distinction isn't blurred (I don't think) by the genes overlapping. Would anyone object to me scrapping "thus bluring the distinction made above between sense and antisense strands"? --Sean T. Smith 19:01, 18 May 2007 (CDT)

Reference Check

If a reference checks out, add the relevant quote, so that your checking can be verified later. If you have access to journals which require a subscription, please prioritise those marked "not checked - no access".

  • 1ab, 2 not checked - no access
  • 3 now fixed: ERROR - based on abstract: source gives 22-26 angstrom (2.2 - 2.6 nm) width
  • 4 not checked - no access
  • 5ab checked OK
    • a quote="The novel feature of the structure is the manner in which the two cheins are held together by the purine and pyrimidine beses. The planes of the bases are perpendicular to the fiber axis. They are joined together in pairs, a single base from one chain being hydrogen-bonded to a single base from the other chain"
    • b quote not applicable
  • 6 not checked - no access
  • 7ab ERROR
    • 7a ERROR - does not seem a suitable source: supporting information may or may not be inferred but suggest replacement with a source that provides it explicitly
    • 7b ERROR - does not provide structural information of nucleotides not explicitly state that A+G are purines while C+T are pyramidines
  • 8ab not checked - no access
  • 9 not checked - no access
  • 10, 11 skipped
  • 12 not checked - no access
  • 13 ERROR - based on pubmed abstract: quote="Cro, repressor, and CAP use alpha-helices for many of the contacts between side chains and bases in the major groove" - suggest this is insufficient to make the assertion that "proteins like transcription factors that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove" - suggest further scrutiny of entire text (no access).
  • 14 checked ok - quote="The situation in nucleic acid systems is somewhat different: from our present model, the analysis of the different contributions seen in Table 2 shows that the components base stacking, hydrogen bonding, and van der Waals terms are the major partners; the relative contributions are 33.4% base stacking, 30.3% van der Waals, 18.2% hydrogen bonding, 12.1% hydrophobic, and 6.1% electrostatic"
  • 15 skipped
  • 16 skipped - too complex
  • 17, 18, 19, 20 not checked - no access
  • 21 checked and article corrected - quote=[N/A; see Table 1]
  • 22ab checked ok
    • 22a - quote="...these short overlapping sequences may be involved in expression regulatory mechanisms"
    • 22b - quote="...approximately a third of all genes in the [microbial] genomes are overlapping..."
  • 23, 24 not checked - no access
  • 25 checked ok - quote="As a linear, single-stranded DNA, the parvovirus genome represents a relatively unusual structure in terms of DNA replication."
  • 26 not checked - no access


Reference Check Discussion

Only a handfull of references have actually been checked, but from those that have, we can see that there are sufficient problems to prevent approving the article until all have been corrected. --Sean T. Smith 06:29, 11 June 2007 (CDT)


Overview

My gut feeling on reading this is that it is still very close to the WP article and has some way to go to be a significant improvement on what is by WP standards a very good article.

I think it is over-referenced and overtechnical for an overview article. The over-referencing is a challenge for editors to affirm that the references are accurate and appropriate choices from a vast literature, but are often used here to support uncontroversial statements that we can safely affirm on our own authority. I wouldn't trim these out myself because it's important to retain them in subarticles. (I wrote this before seeing Sean's comment above, after reading it I think even more strongly that we should radically reduce the references)

The article, despite its length, lacks an account of regulation of gene expression. It perhaps should also contain an estimate of the number of genes in the genomes of different species. On the forensic side, I think DNA fingerprinting needs some extra explanation. I think DNA computing should go straight into a separate article, it really is a very minor field at present.Gareth Leng 06:36, 11 June 2007 (CDT)

I think you have to be careful here. If we just start stripping away references, we might end up leaving in erroneous information because we didn't notice that the reference actually said something different. Take reference 3 for example. Before I checked it, two researchers in the field at Wikipedia had already gone over the article and not noticed the small error (I wouldn't have expected them to and that is exactly my point). Although there may be experts involved in this, experts aren't infallable, and without checking references, we could be leaving in false material, that due to lack of a reference (it having been already removed), is not noticed for a long time, if at all.
Stripping out references would be one way of reducing the workload, but that could come at the cost of quality of the finished article. --Sean T. Smith 09:15, 11 June 2007 (CDT)

Modify it drastically, incorporate the more recently imported version, we would have started with that, but... Make the changes that you envision. We have until the 21st. Nancy Sculerati 09:19, 11 June 2007 (CDT)

Ch-ch-ch-ch-changes

I rewrote intro, stuck two new subheadings Genes, because we should explain them before we talk about them, and Regulation of gene expression, because that idiosyncratic Englshman (or is he a Scott, yet?) insists that it has some kind of importance. (go figure). In my honored and august opinion, we should carry on and not worry about the fact that obviously, we have the daunting task of explaining the big story, and also presenting the details. I refuse to be blind-sided by the linear thinking that argues: gee, you can't talk about gene regulation unless you explain methylation in detail. You and I can, and we will, and by the end, we'll have moved things around and clarified so this might actually be a lot of fun. Shoulkd we expalin such things as methylation in detail, we will have placed the audience in a coma- instead, we have to make the mystery acute- just how could that second X chromosome get inactivated (sorry, boys, don't mean to rub it in), and make the details the denouement of the mystery- not a sedative in the intro. So- hold on to your hats, this is likely to be a bumpy ride. If ever "Be bold" applied-it's to this clunker of an article. Nancy Sculerati 10:01, 11 June 2007 (CDT)

Copyedit, please, before approving. I caught two things in the introductory section without even trying. --Larry Sanger 10:24, 11 June 2007 (CDT)

Well, Sean is very concerned with reducing workload, and Larry has carefully bolded the intro, I am taking a 2 week break. Copyedits? The article is being written, it's only been moved for approval because it is so imprtant and needed our attention. There was another article- but it's too hard to simplify adequately so that explaining the duplicate effort in articles can be followed with minimum effort and capacity. I am removing my name from approval, since I will not be on the wiki to get the article into shape. Nancy Sculerati 11:23, 11 June 2007 (CDT)

OK, it's the simple things that catch us out.

"The genetic information in a genome is held within genes. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism."

At the outset I think we need to explain what a gene is more clearly, and to explain what we mean by gene expression. I think we need to explain that the protein coding regions of genes are flanked by regulatory elements to which transcription factors bind to regulate gene expression. The point here is that perhaps most heritable information is carried in these non-coding regions adjacent to coding regions, and in practice it is differences in these regions that most commonly affect phenotype. In most species, heterogeneity in the coding regions is I think very rare. ? So, the sentence above, though often expressed in this way in textbooks, is just multiply wrong if genes are taken to be just the protein coding sequences.

In what sense a gene is really a unit of heredity I'm not clear.

I've deleted a few references and some detail to guage opinion on policy here. I think though that it's possibly more of a challenge to explain the basics clearly and accurately than to provide detail. My instinct would be to cut deep into the references but expose some of the basics (as above) to more careful thoughtGareth Leng 11:58, 11 June 2007 (CDT)


Genes and Cre lox-

I quickly drafted a genes and regulation section. Change them as much as you like.

WE NEARLY GOT INTO TROUBLE WITH A WIKI PEDIA AMATEUR EDIT CARRY OVER ON CRE LOX

Impportantly while throwing in a link to Cre loxP recombinase, I realised there are serious factual errors in the Genetic recombination section. Homologous recombination is interupted by Cre-lox which are not involved in homologous recombination. Im going to have to fact check in detail the whole mess but not tonite. I need to check for certain which enzymes are involved in homologous rec. (RAD51 OK? this is a yeast enzyme, and i think abent from E coli) Cre lox is definitely wrong here though. Ive commented out the problem text to simplify re-editing . It doesnt help that homologous recombination is one of my weakest areas of genetics knowledge David Tribe 07:01, 12 June 2007 (CDT)

David, see this edit i made earlier [1] I guess that did not get incorporated. Obviously I agree RAD51 is a good example. Cre is a bacteriophage recombinase, specifically designed for the integration and excision of DNA for one particular phage. It has nothing to do with meiosis. Chris Day (talk) 11:03, 12 June 2007 (CDT)
Now i understand what happened after looking through the edit history. I had replaced Cre with RAD51, but this edit here adds RAD51 as an additional example to Cre recombinase. Chris Day (talk) 15:47, 12 June 2007 (CDT)

Havnt done much myself lately

But I like the way the earlier sections are shaping up a understandable description of core simpler topics. It what i had in mind (but didnt achieve by myself) when I first started meddling with the WP version. Thanks . David Tribe 23:31, 13 June 2007 (CDT)


But I realised when reading through the mention of toucvhing on technology we should mention plasmids and molecular cloning. I can do this easily, and should flesh out a short section mentioning plasmids, restiction enzymes and recominant DNA very easily in the next day or so. But if others see fit jump in. David Tribe 21:21, 14 June 2007 (CDT)

Introduction comments

1) "In most organisms, DNA is a double-helix (or duplex molecule) consisting of two complementary DNA strands coiled around each other, and held together by hydrogen bonds between bases."

Ok, please enter the exceptions in a very short sentence after this sentence.
Short answer is some viruses and phage ( Parvoviridae and bacteriophage M13). Chris Day (talk) 00:08, 16 June 2007 (CDT)

2) Mitochondrial DNA is not mentioned in the introduction.

Tom Kelly 20:30, 15 June 2007 (CDT)

Organelle genomes should probably be mentioned somewhere. Let's not forget chloroplast have DNA too. Chris Day (talk) 00:17, 16 June 2007 (CDT)

Where is the bit about evolution in to DNA from an earlier form of genetic code

I'm pretty sure I remember from IntroBio that DNA evolved from earlier forms of genetic code. I believe the order was first protein building blocks, then RNA building blocks, then finally evolved in to DNA. It would be interesting to comment on the benefits of DNA as the basis of genetic code verses these other forms. Maybe I'm completely off. Does it say anywhere in the article about the stability of DNA vs RNA? Tom Kelly 20:37, 15 June 2007 (CDT)

This may be too speculative for this article. Chris Day (talk) 00:06, 16 June 2007 (CDT)
Ok, then maybe a link to a different article. Tom Kelly 12:17, 18 June 2007 (CDT)
Possibly an article titled Genetic code? Chris Day (talk) 13:14, 18 June 2007 (CDT)


Theres a lot of stuff in the literature on this. I agree Tom's comments are largely speculation. Some propose parallel evolution of the RNA world and the peptide world. There is an important paper by Dieter Soll Nov 2007 PNAS on the evolution of protein coding, arguing that the code preexisted its current role in aa adaptation. David Tribe 22:15, 20 June 2007 (CDT)
November 2007? Nice crystal ball you have there David. I assume this is the paper [2] The major point he is trying to make is that the genetic code predates the aminoacyl-tRNA molecules. This ties in with the ideas that Woese outlined in his article The Genetic Code. New York: Harper & Row; 1967 where he argued "that protein enzymes with enough specificity to interpret the genetic code could have been produced only by a translation apparatus accurate enough (even if not as precise as that found in modern cells) that an established code would have been required to produce such proteins." (direct quote from Söll's paper). Of course this is only one part of the story. Chris Day (talk) 03:14, 21 June 2007 (CDT)

Abbreviations

Isn't mitDNA the proper abbreviation for Mitochondrial DNA? I do not see by my cmd+f search of the article Tom Kelly 20:41, 15 June 2007 (CDT)

I've always abreviated it mtDNA. Chris Day (talk) 00:05, 16 June 2007 (CDT)

Epigenetic

The word epigenetic needs to be formally explained or at least appear somewhere in the article. It is listed in one reference but this is the up and coming field that must be mentioned formally somewhere. Tom Kelly 20:43, 15 June 2007 (CDT)

X-inactivation is mentioned in the DNA#Base_modifications section. Remember the term epigenetic is used to explain differences of expression with no change in the DNA sequence. This might be better in a daughter article on chromatin or gene expression.Chris Day (talk) 00:15, 16 June 2007 (CDT)
I guess maybe an example of clinical relevance or biological relevance to epigenetics would be nice. I just would like it if someone comes to this article and does cmd or cntrl +f for "epigen..." that they should come across at least a link to another article. Epigenetics is changing how we fight cancer and view addiction so it's pretty interesting stuff. Tom Kelly 12:21, 18 June 2007 (CDT)
I suspect the Also see: (or what ever we call it) section might be the best place. Or a brief mention in the base modifications section. Remember there are plenty of examples of epigenetic control at the histone level ONLY so access to DNA sequences by regulatory proteins and RNA might be more important than DNA-modifications, for the diseases you mention. Chris Day (talk) 13:13, 18 June 2007 (CDT)

ENCODE

I'm not too keen on the changes involving this recent ENCODE paper in nature. I have not read the paper yet, so I do not know enough yet to evaulate the additions. However, we must remember that just becuase a region is transcribed does not mean it has a function. Or, if it does have a function, such as epigenetic feed back to control the chromatin state (heterochromatin in centromeres represents one example) these RNA molecules would not be described as exons. The value of 1.5% for exons (or whatever it was that got changed) is probably valid even if we find there are more transcribed regions than originally realised. Chris Day (talk) 00:30, 16 June 2007 (CDT)

I disagree. Genome biology is moving exceptionally fast, but the ENCODE material in Nature and in the issue of Genome Research is quite well vetted and is showing that much of the information included in previous versions of this article are simply wrong. I think the main point is that the information coming from Venter et al.s draft sequence paper in 2001 is largely incorrect with regard to the "functionless" untranscribed highly repetitive sequences. Turns out that the majority of these regions ARE transcribed and PROBABLY DO have a function. John J. Dennehy 11:36, 17 June 2007 (CDT)
Let me read the paper. I have my doubts without immersing myself in the data. Don't forget that Pruit's work on RNA caches was all over the news when it first came out. It has subsequently be challenged and his data appears to be flawed. One paper does not knock down a dogma. What is the function for all these extra transcribed sequences? The only well doucmented one, that I am aware of, is for maintaining the heteromeric structure of the centromeres. Even if the old dogma is incorrect, we cannot just delete it from the article since the dogma is so ingrained in all text books. There would have to be some discussion of old view vs new view until it was well accepted. Having said all that, now I should go and check the paper. Chris Day (talk) 16:48, 17 June 2007 (CDT)

I have read the paper (free access found here), which is mammoth and while interesting much is speculation based on the data from the pilot phase. With regard to the massive increase in functional DNA they have this to say.

"We have encountered a remarkable excess of experimentally identified functional elements lacking evolutionary constraint, and these cannot be dismissed for technical reasons. This is perhaps the biggest surprise of the pilot phase of the ENCODE Project, and suggests that we take a more 'neutral' view of many of the functions conferred by the genome."

I think this is too premature to taken precedence in a general article on DNA and certainly should not supplant much of what is known about functional elements in a typical genome. They are basing their conclusions on an assumption which I believe to be flawed. The survey is looking at primary transcripts and the assumption is that these are functional. After reading their paper they have not presented an argument for why this assumption is valid.

Four related quotes from the paper are:

'""The detection of numerous unannotated transcripts coupled with increasing knowledge of the general complexity of transcription prompted us to examine the extent of primary (that is, unspliced) transcripts across the ENCODE regions."
"Remarkably, 93% of bases are represented in a primary transcript identified by at least two independent observations."
"[their studies confirm] the presence of substantial intragenic and intergenic transcription. At the same time, many of the resulting transcripts are neither traditional protein-coding transcripts nor easily explained as structural non-coding RNAs."
"The biological relevance of these unannotated transcripts remains unanswered by these studies."

This last one is as I expected, they are speculating that ALL the primary transcripts have a function. It should not be hard for biologists to accept that transcription is quite sloppy and the splicing process is important for the primary transcript to resolve to a functional subset. The paper spends a lot of time trying to postulate why so many functional transcripts are unconstrained from an evolutionary perspective. Not once do they consider it might be due to the fact they are non-functional.

I do not deny that the data they are showing is good, but to assume there is a function with no basis for such a claim seems to be a bit sensational. It seems more designed to get attention from newspapers and get the politicians excited; a good way to secure future funding, I might add. Time will tell if all these primary transcripts have a function, but in my opinion, this DNA article needs to be wary of jumping on this band wagon. Chris Day (talk) 13:03, 18 June 2007 (CDT)

Any response to the points that I made here? If not, i assume no one will mind if I rewrite the article to deemphasize the ENCODE project. Chris Day (talk) 02:57, 21 June 2007 (CDT)
I agree. The text in the article closely and accurately follows the press release [3]; I think the paper itself is much more cautious in its discussion, and I agree with Chris that at present caution beyond that of the authors is appropriate at present.Gareth Leng 10:03, 22 June 2007 (CDT)
I havent read the paper but can follow Chris's argument. We should be conservative for now and follow Chris' lead, IMHO. David Tribe 18:30, 1 July 2007 (CDT)

adding see also section. please move to correct location

I'm adding a "see also" section. Please move it to the correct location. Tom Kelly 13:43, 30 June 2007 (CDT)

Should the references be at the very bottom of the article? Tom Kelly 13:49, 30 June 2007 (CDT)
Also, I added two links to CZ article topics which are not yet written yet, but I thought are needed links. Feel free to change the name of the links/articles. I just want the word "epigen-" (as in epigenetics) to appear somewhere in the article besides a reference. Tom Kelly 13:49, 30 June 2007 (CDT)

Lead paragraph

"Yet, there are many types of macromolecules in living things, and there exists all sorts of chemical variability between them at any one time. We know, as experimentally proven fact, that nearly all classes of macromolecules show variations between the generations in the most rapidly reproducing organisms, bacteria, and we must assume that there are similar changes in the biochemistry of each kind of living thing, including those with long generation spans, over all the ages of life on earth. "

This is currently the core of the opening paragraph. What is the take home point of this section? That there are mutations? That there are different alleles in a population? I find it pretty confusing and I think this will switch off the interest of the average reader. It needs to be more transparent. Chris Day (talk) 11:04, 2 July 2007 (CDT)

OK, I tracked down this change to a series of edits that Nancy made. [4] Am I the only one that finds the intent foggy here? I note she also removed a fairly brief history section as well as a section on DNA computing that i will try and reincorporate in to the last section. I wonder if a brief history section might be appropriate? Chris Day (talk) 11:54, 2 July 2007 (CDT)
I just made some changes to the lead see what you think. It still needs work. Chris Day (talk) 12:08, 2 July 2007 (CDT)


Do we want to axe the history section?

In the following series of edits Nancy axed the history section.[5] My guess is that many readers come to DNA from a historical perspective so might like to see that context presented, even if very briefly. I have cut and paste the section into this talk page here:


Further information: History of molecular biology

DNA was first isolated by Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".[1] In 1929 this discovery was followed by Phoebus Levene's identification of the base, sugar and phosphate nucleotide unit.[2] Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. However Levene thought the chain was short and the bases repeated in a fixed order. In 1937 William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.[3]

In 1943, Oswald Theodore Avery discovered that traits of the "smooth" form of the Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. Avery identified DNA as this transforming principle.[4] DNA's role in heredity was confirmed in 1953, when Alfred Hershey and Martha Chase in the Hershey-Chase experiment, showed that DNA is is the genetic material of the T2 phage.[5]

In 1953, based on X-ray diffraction images[6] taken by Rosalind Franklin and the information that the bases were paired, James D. Watson and Francis Crick suggested[6] what is now accepted as the first accurate model of DNA structure in the journal Nature.[7] Experimental evidence for Watson and Crick's model were published in a series of five articles in the same issue of Nature.[8] Of these, Franklin and Raymond Gosling's paper[9] saw the publication of the X-ray diffraction image [10], which was key in Watson and Crick interpretation, as well as another article, co-authored by Maurice Wilkins and his colleagues.[11] Franklin and Gosling's subsequent paper identified the distinctions between the A and B structures of the double helix in DNA.[12] In 1962 Watson, Crick, and Maurice Wilkins jointly received the Nobel Prize in Physiology or Medicine (Franklin didn't share the prize with them since she had died earlier).[13]

In an influential presentation in 1957, Crick laid out the "central dogma" of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".[14] Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson-Stahl experiment.[15] Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code.[16] These findings represent the birth of molecular biology.


So what do you think? Does some form of this, possibly reduced in size, belong in this article or not? or should we just have a History of DNA article linked from the Also see section? Chris Day (talk) 12:13, 2 July 2007 (CDT)

  1. Dahm R (2005). "Friedrich Miescher and the discovery of DNA". Dev Biol 278 (2): 274-88. PMID 15680349.
  2. Levene P, (1919). "The structure of yeast nucleic acid". J Biol Chem 40: 415-24.
  3. Astbury W, (1947). "Nucleic acid". Symp. Soc. Exp. Biol 1 (66).
  4. Avery O, MacLeod C, McCarty M (1979). "Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Inductions of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III". J Exp Med 149 (2): 297-326. PMID 33226.
  5. Hershey A, Chase M (1952). "Independent functions of viral protein and nucleic acid in growth of bacteriophage". J Gen Physiol 36 (1): 39-56. PMID 12981234.
  6. 6.0 6.1 Watson J.D. and Crick F.H.C. "A Structure for Deoxyribose Nucleic Acid". (PDF) Nature 171, 737 – 738 (1953). Accessed 13 Feb 2007.
  7. Cite error: Invalid <ref> tag; no text was provided for refs named Watson
  8. Nature Archives Double Helix of DNA: 50 Years
  9. Molecular Configuration in Sodium Thymonucleate. Franklin R. and Gosling R.G.Nature 171, 740 – 741 (1953)Nature Archives Full Text (PDF)
  10. Original X--ray diffraction image
  11. Molecular Structure of Deoxypentose Nucleic Acids. Wilkins M.H.F., A.R. Stokes A.R. & Wilson, H.R. Nature 171, 738 – 740 (1953)Nature Archives (PDF)
  12. Evidence for 2-Chain Helix in Crystalline Structure of Sodium Deoxyribonucleate. Franklin R. and Gosling R.G. Nature 172, 156 – 157 (1953)Nature Archives, full text (PDF)
  13. The Nobel Prize in Physiology or Medicine 1962 Nobelprize .org Accessed 22 Dec 06
  14. Crick FHC On degenerate templates and the adaptor hypothesis (PDF). genome.wellcome.ac.uk (Lecture, 1955). Accessed 22 Dec 2006
  15. Meselson M, Stahl F (1958). "The replication of DNA in Escherichia coli". Proc Natl Acad Sci USA 44: 671-82. PMID 16590258.
  16. The Nobel Prize in Physiology or Medicine 1968 Nobelprize.org Accessed 22 Dec 06