Talk:DNA

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)

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:

---

Francis Crick

James Watson in the Cavendish Laboratory at the University of Cambridge.

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". In 1929 this discovery was followed by Phoebus Levene's identification of the base, sugar and phosphate nucleotide unit. 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.

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. 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.

In 1953, based on X-ray diffraction images taken by Rosalind Franklin and the information that the bases were paired, James D. Watson and Francis Crick suggested what is now accepted as the first accurate model of DNA structure in the journal Nature. Experimental evidence for Watson and Crick's model were published in a series of five articles in the same issue of Nature. Of these, Franklin and Raymond Gosling's paper saw the publication of the X-ray diffraction image , which was key in Watson and Crick interpretation, as well as another article, co-authored by Maurice Wilkins and his colleagues. Franklin and Gosling's subsequent paper identified the distinctions between the A and B structures of the double helix in DNA. 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).

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". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson-Stahl experiment. 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. 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)

I'd go for a separate article as the present one is getting unwieldy. This article seems pretty good to me, but there are some obvious basic questions that it leaves unanswered, and in so doing invites misconceptions.

First, I think that, in popular understanding, genes are things that make one person different from another, whereas we tend to think of genes as the things that make individuals of a species like each other but different from individuals of other species. I think it would be useful to explain a bit about alleles. It might also be useful to indicate quantitatively just how different one human is from another, and how different we are from other species.

Second, the idea that DNA encodes a functional blueprint seems at odds with the idea that every cell of an organism, however different they are carries the same DNA. I think it might be useful to explain that DNA is regulated in a cell-specific manner - so although all cells carry the same DNA, different cells express different proteins.

Third, I think the concept of homology is very important for understanding how DNA analysis provides evidence of evolution, and could do with highlighting for explanation.

Overall, I think the article is very dense in technical terms. This is not a criticism in itself, it's unavoidable, but it does mean it is hard to see which technical terms are the ones that are really important for the reader to understand, and which can be "read past".Gareth Leng 06:03, 3 July 2007 (CDT)

I agree with the blueprint analogy being a stretch. Personally I have always used the library analogy. Chromosomes are shelves, genes are books. Still not great but getting closer. Each book is transcribed (photocopyed) and translated (instructions are read from the text) and used for the better of the community (the cell), whether it is to mend the house or knit a sweater. Clearly not all books in a library are used all the time, or ever. The question is do we want to fold a good analogy into the narative, like the computer one above, or not. It might be a nice touch to attract the attention of younger readers. As always no analogy is perfect and might lead to misconceptions. Chris Day (talk) 09:55, 3 July 2007 (CDT)

More axeing?

I suggest dropping the DNA computing section as a) its all from WP, b) it's tangential to everything else c) it's not really comprehensible except to a specialist readership and d) it's a pretty minor activity at present. Suggest seeding a separate article with this, but excluding it here? The section is below.Gareth Leng 06:11, 3 July 2007 (CDT)

DNA was first used in computing to solve a small version of the directed Hamiltonian path problem, an NP-complete problem. DNA computing is advantageous over electronic computers in power use, space use, and efficiency, due to its ability to compute in a highly parallel fashion (see parallel computing). A number of other problems, including simulation of various abstract machines, the boolean satisfiability problem, and the bounded version of the travelling salesman problem, have since been analysed using DNA computing. Due to its compactness, DNA also has a theoretical role in cryptography, where in particular it allows unbreakable one-time pads to be efficiently constructed and used.

Recent edits

I've gone through a last time (last for me) with a mild trim and adjustments mainly to sections from WP that seemed dense in detail and light on clarity. Revert anything without hesitation.Gareth Leng 06:54, 3 July 2007 (CDT)

Gareth, all those changes look great. Chris Day (talk) 09:48, 3 July 2007 (CDT)

Last bits... I took out the Further Information links as these were nearly all red. Thought it seemed a bit perverse to approve an article that had too many links to nowhere. Gareth Leng 12:03, 3 July 2007 (CDT)

polymer not macromolecule

Strange this persistency to predominately call DNA a polymer, where a polymer (generally) is a molecule not soluble in water unless chemically modified. A polymer basic appearance is a solid, where as a macromolecule per definition can form an aqueous solution and dissolves in water - having hydrogen-bonds between the solute and solvent stabilize its conformatiuon, or function. The way to prepare a polymer is by reactions, to prepare a solid macromolecule it needs extraction from biological sources. In general a polymer is soluble in an organic (mostly benzene-based) solvent. Generally biological functional polymers are referred to as macromolecules (See the papers from the IUPAC conference in Bucarest-Romania 1985 where this discussion was settled.). Robert Tito |  Talk  23:48, 4 July 2007 (CDT)

??

If it was settled, biologists didn't seem to notice, and the IUPAC commission on macromolecular nomenclature seems to have accepted this, at least by 1996.

from IUPAC[6]

"MOLECULES AND MOLECULAR STRUCTURE

1.1 macromolecule

polymer molecule

A molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass."Gareth Leng 03:36, 5 July 2007 (CDT)

I don't see the problem with polymer. It is just a more general term for polynucleotide. Also the term seems to be more specific than macromolecule which could also include non-polymers. Biopolymer is a potential compromise, if this is a real problem. Chris Day (talk) 13:00, 5 July 2007 (CDT)

the main difference in practical use (the terms refer to the same) is a macromolecule indicates a water soluble polymer (often used in a biological sense), when extracted in dry form it is crystalline and the nature it that of a polyelectrolyte. Contrary a polymer generally refers to the repetitive continuation of mostly one group leaving a non-water soluble polymer (nylon and plastics being examples), generally without a biological function. This minor difference is used in my country and by me for over 20 years now and leaves unaltered the fact that macromolecules are polymers and vise versa. It describes the nature more quickly as many people automatically combine a polymer with a plastic and a macromolecule to some biological protein. A small detail is conformation and configuration, and the solvent. Robert Tito |  Talk 

APPROVED Version 1.0

Discussion for ID Version 1.0 stopped here. Please continue further discussion under this break.

Congratulations everyone!  —Stephen Ewen (Talk) 01:21, 7 July 2007 (CDT)

NOTE: Redirects pointing to DNA/Questioned and Talk:DNA/Questioned were overwritten during the approval.  —Stephen Ewen (Talk) 01:25, 7 July 2007 (CDT)

Chris added a speedydelete to DNA/Questioned but also seemed to want the input of other editors on the matter. What say you?  —Stephen Ewen (Talk) 13:40, 7 July 2007 (CDT)

See User_talk:Sean_T._Smith#DNA.2FQuestioned for what I ended up doing with it.  —Stephen Ewen (Talk) 01:20, 8 July 2007 (CDT)

Proposed Sentence Cut

Re: sentence: Many 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), blurring the distinction 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)

its ok to delete I think David Tribe 08:00, 14 July 2007 (CDT)

Comment

http://forum.citizendium.org/index.php/topic,1099.0.html --Larry Sanger 09:16, 26 July 2007 (CDT)

DNA is most correctly called a polymer of deoxyribonucleotides. The deoxyribonucleotide subunits each contain a nitrogenous base (A,C,T or G), a sugar (deoxyribose) and one phosphate group, but can have more phosphates in the monomeric state, such as in Adenine triphosphate. (See Biochemistry,3rd Edition, by Lubert Stryker, p72, Freeman and Co. NY 1988)

A Compound, by definition, is a substance composed of more than one element, chemically combined (as opposed to a mixture) so compound is acceptable for DNA, but is not the best description.

David E. Volk 13:25, 26 July 2007 (CDT)

Error in article?

See http://en.wikipedia.org/wiki/Talk:DNA#Citizendium_version_of_this_article  —Stephen Ewen (Talk) 22:18, 2 September 2007 (CDT)

Significant Discovery

Would like to include this information in the article

Note (Kornberg won the Nobel prize in chemistry for his discovery of how DNA can be spliced)

---

Arthur Kornberg DNA Replication Freeman and Co 1980 Page 2

Chapter 1 Structure and Functions of DNA

1944-1960 The Genetic Substance

This "Golden age" began with the first important evidence that DNA is the genetic substance...

Two persuasive discoveries were eventually made. The first was the demonstration in 1952 that infection of Escherichia coli by T2 bacteriophages involved injection of the DNA of the virus into the host cell. The viral protein structures appeared to serve merely to inject the DNA into the bacterium and then to be largely discarded outside the cell. The DNA from the virus thus directed the bacterial cells to produce many identical copies of the infecting virus. This experiment dramatized the role of DNA as the carrier of information for -producing the unique proteins of the virus and for duplicating its DNA many times over."

Thomas Mandel 14:48, 26 February 2008 (CST)

Significant Observation

Would also like to add this significant observation, also written by Kornberg

“The most important feature of the duplex model for DNA structure is the introduction of the concept of complementarity. It provided the explanation for accurate replication of a very long chain. This inherent feature of DNA is the basis not only of its replication, but also of its capacity to transmit information. Complementarity has come to explain transcription and translation and thus the entire sequence of events in the expression of genetic functions. It is also the basis for exchange of DNA segments between chromosomes in several forms of recombination.” P13

Thomas Mandel 14:52, 26 February 2008 (CST)

Style changes

I wonder who the intended audience of this DNA article is? Does an article written by experts automatically imply that the audience is likewise expert? Would an expert be referring to this article as it is written here? Or is the intended audience someone rather new to DNA, like me. My interest in DNA, however, is not so much how it works in detail, but what does it do in general? I also am interested in how DNA was discovered and how is it being investigated today. For example, I think it is significant that biologists once believed that it was impossible for DNA to be the genetic material because it consisted mainly of a few repeating molecules. They believed instead that the genetic material had to be the more complex protein molecule. So it is very interesting that they were able to isolate the interaction of DNA from a protein, and doing so discover that it is DNA and not protein that is the genetic material. Kornberg writes that this discovery is one of the first two significant abvances in DNA research.

And then there is complementarity. My early edits about this were retained, but since that early time I found this book written by Arthur Kornberg, the fellow who discovered how to splice DNA back together again. Being a systems thinker, I think it is very significant that Kornberg has observed that the entire DNA process is complementary. In the weak significance complmentarity is how the DNA is self correcting or error free. But in the strong sense, DNA complementarity at least suggests that all of life is complementary. (See symbiosis, etc.))

This is in stark contrast to the prevailing standard view that life is accidental and competitive, that it is the living that have not died.

So what I am leading up to is the suggestion that there are disadvantages of authorship by experts. The disadvantage is that experts tend to write for experts. Their entire training experience is to impress other experts. So I wonder what is more important, to write an article which really would not be enlightening to an expert, or write an article which would be enlightening to a non expert.

Thomas Mandel 21:57, 28 February 2008 (CST)

Rearrange draft article

Would it be OK if I reorganized the first few paragraphs? As they stand now, the really important aspect of DNA, how it replicates, isn't mentioned until well into the article. Can I rearrange the paragraphs just to see how they would turn out? If it doesn't work then it can be simply reverted back. OK?

I haven't received a reply or objection, so I am assuming that there is no problem so far. I am going to attempt to improve the readability of the article on the draft page. at this time I will not be making any changes to the text. Thomas Mandel 08:59, 29 February 2008 (CST)

OK, I rearranged the first few paragraphs mainly to connect concepts. I hope all will agree that it is much better. Now I would like to make some changes to the text, and will at this time only propose them. First, in the first paragraph, I question the satement

"This inheritable variation in DNA is the most important factor driving evolutionary change over many generations."

The statement reads as if it is a fact, when in fact it, (the most important factor driving evolutionary change ), is a theory derived from Darwinian evolution. The problem is the word "most important". While many would agree, there are some who do not agree proposing instead that "self-organization" is important. The sentence as it now reads is very tricky because at first glance it sounds correct but has many implications if one reads between the lines. Also, what is "This inheritable variation" referring to"

I also question the statement ---

"But, beyond these general characteristics, what "exactly" is DNA? What are the precise physical attributes of this molecule that make its role so centrally imposing in understanding life?"

Again, technically the sentence is not incorrect but is it really necessary here? We have three sentences at the very beginning which confuse rather than enlighten. I would like to propose the three be taken out so that it reads like so ---

"Deoxyribonucleic acid (DNA) is a very large biological molecule that is vital in providing information for the development and reproduction of living things. Every living organism has its own DNA sequence that is like a unique 'barcode' or 'fingerprint'.

"DNA is a long polymer comprised of simple units called nucleotides which are..."

Thomas Mandel 09:32, 29 February 2008 (CST)

I don't mean to diminish the importance of DNA, but importance was stated in the first sentence and it would be better, I think, if this importance be elaborated on in a separate paragraph at a more appropriate location in the article. I think an explanation of how and why DNA was discevered would be very interesting and illustrative of the scientific method, and the importance could be emphasized there. Thomas Mandel 10:04, 29 February 2008 (CST)

I am going to remove these sentences and place them here

"This inheritable variation in DNA is the most important factor driving evolutionary change over many generations. But, beyond these general characteristics, what "exactly" is DNA? What are the precise physical attributes of this molecule that make its role so centrally imposing in understanding life? "

I object to the first sentence because the referant is not clear, and it is stated as a fact when it is only part of a theory, and the most important purpose of DNA is to replicate without error or changes; and while some do believe that random mutations drive evolution others believe that self organization is most important. It is at the very least out of place. The next two sentences seem to me to be trivial and therefore confuse rather than enlighten. Of course someone reading the article is asking those questions, It would be much bettter if the answers to those questions are inserted. Thomas Mandel 11:07, 1 March 2008 (CST)

Hi Tom. I think you should go ahead; the article can certainly be improved (can't all articles?) and this is a draft page to try things out. Sometimes it's best to just make changes and then see how they sit in context - it's not easy to judge these line by line.

You questioned the following line though: "This inheritable variation in DNA is the most important factor driving evolutionary change over many generations." Whether this is true depends on how it is read, and on some readings this is absolutely accepted theory, but I certainly think it could be altered and be clearer. The sentence does not in fact refer to random mutation, but simply refers to natural selection working through selection from inherited variability. I don't see how self organisation can drive evolution, and don't know of any mainstream support for this. Certainly self organisation is a product of evolution, and an important feature of complex systems. The following two questions were really written (I think probably by Nancy Sculerati) to "set the agenda" for the article - whether that agenda was in fact followed effectively is certainly questionable, but I think the intent was good. But go ahead, make your changes and let's just see how they sit on the page. We may not like them all.... but again, this is a draft article, so try it.Gareth Leng 08:01, 2 March 2008 (CST)

OK, I reworked the first three paragraphs for readability. I hope you like it.Thomas Mandel 14:47, 2 March 2008 (CST)

Can we hold off inserting inherited variability? The sentence is confusing to me and makes a lot of assumptions. I think it is true as you say, but for one I think it is out of place and selection as the evolutionary driver has been disputed mainly because it occurs after the evolutionary change occured. The real question then is how did the change come about to begin with? How did the amino acids form the proteins to form a ribosome needed to form the proteins accidently? Thomas Mandel 15:04, 2 March 2008 (CST)

recent changes

In general I agree with the rearrangements, however, the new lead doesn't read correctly. The (whole) code is not a gene, and the major role is to synthesis proteins, not amino acids. David E. Volk 18:35, 2 March 2008 (CST)

Corrections have been made. Interestingly, my perspecive was from that of the gene. I am working from Kornberg's text and he doesn't make it clear exactly what DNA is doing in his introduction. For example he cites the two major functions-- "One is to carry the genetic information that brings about the specific phenotype of the cell." Then he explains briefly how this happens, then he mentions # two which is replication.Thomas Mandel

Looking up a definition I find this "The "internally coded, inheritable information", or Genotype, carried by all living organisms, holds the critical instructions that are used and interpreted by the cellular machinary of the cells to produce the "outward, physical manifestation", or Phenotype of the organism. Thomas Mandel

I find these two sentences placed together quite interesting. Kornberg's assumes that the meaning of phenotype is known while the second web definition actually defines it. Basically this is what I hope to accomplish - to write the article such that it is instructive as well as informative. Not saying that I was aware of this purpose before seeing these sentences.Thomas Mandel 19:35, 2 March 2008 (CST)

How do I copy this?

"The "internally coded, inheritable information", or Genotype, carried by all living organisms, holds the critical instructions that are used and interpreted by the cellular machinary of the cells to produce the "outward, physical manifestation", or Phenotype of the organism."

Should I paraphrase it? Can I just copy it? How do I incorporate a well written sentence into our text? Is there such a thing as generic information where copyright does not enter into question? This has been a huge ongoing problem for me. Usually paraphrasing screws it all up. Thomas Mandel 20:04, 2 March 2008 (CST)

Well, what if I turn it around?

The Genotype, or internally coded, inheritible information which all living organisms carry , provides the necessary instructions the cell requires to produce the Phenotype or outward physical manifestation of the organism.

Thomas Mandel

Are the changes pleasing?

The changes I made are too mumerous to mention here, but the acid test is a reading up to the section on replication. I had moved replication up from where it was below genes mainly because the section on genes is very detailed. There is a problem as I read further.

A problem/omission?

This sentence

"However, occasionally mistakes (called mutations) occur, contributing to the genetic variation that is the raw material for evolutionary change.

The problem is that many mistakes occur daily and there are several different ways DNA is repaired. I haven't found, yet, any mention of this natural repair process in the article. Second, while mutations is covered later, I wonder if those changes that occur in bacteria for example can rightfully be called mutations. At least mutations of the random kind. If mutations means changes, the the above sentence is valid. But in the case of bacteria changing itself to avoid certain drugs, I doubt that it could be called a "mistake." That is, does a "mistake" result in an evolutionary change? Is it really possible that one mistake in one cell in one organism could become an inheritable factor over a period of several if not hundreds of generations? Do we find that genetic diseases multiply? Or are wiped out?

Thomas Mandel 00:51, 3 March 2008 (CST)

Regarding drugs and bacteria. The resistance can come about from gene swapping with other bacteria, or one of the random (not mistaken or planned) mutations just happens to provide for better survival under the conditions of drug being present. Mutations are usually due to several changes. First, damage occurs, such as oxidative damage or the formation of a DNA adduct with a polyaromatic heterocycle. This happens thousands of times a day per cell, but most of these are fixed by the nucleotide excision repair (NER) pathway. However, a small number do not get fixed, sometimes leading to mutations during the next replication cycle to the new daughter DNA strand.

For organisms that reproduce assexually, the mutation goes on "forever". However, one of the advantages of sexual reproduction is the ability to get two sets of genes, so the mutation can be wiped out, or be carried on, depending on which gene is passed down from each parent. David E. Volk 09:01, 3 March 2008 (CST)

Moving to article?

Haven't heard any objections, corrections have been made. Can only assume copy is acceptable. Moving to actual article.

Hi Thomas, don't forget to get the draft re-approved before moving anything to the actual article, if this is what you mean. The re-approval process is exactly the same as the approval process. --D. Matt Innis 09:01, 4 March 2008 (CST)

Well, I don't know what the procedure is. So I will continue to work here Thomas Mandel 01:28, 5 March 2008 (CST)

That's the idea. Then when you are finished, either get one editor who has not edited here or three editors who have to nominate the draft to replace the original. It's basically the same as the first approval process. Feel free to ask me when you get to that point and I'll see if I can help. D. Matt Innis 18:04, 6 March 2008 (CST)

Thank you. Thomas Mandel

History of DNA

To help me out I have copied the original history section from above to to here from which I will include what I had left out in my version. Seems that the various sources tend to leave out this or that person. In Kornberg's text, he mentions the discoveries but doesn't mention who made them. What I am trying to do is tell the whole story as short as I can. Much like an outline.Including not only who and when but how. Thomas Mandel 21:00, 6 March 2008 (CST)

---

Francis Crick

James Watson in the Cavendish Laboratory at the University of Cambridge.

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". In 1929 this discovery was followed by Phoebus Levene's identification of the base, sugar and phosphate nucleotide unit. 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.

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. 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.

In 1953, based on X-ray diffraction images taken by Rosalind Franklin and the information that the bases were paired, James D. Watson and Francis Crick suggested what is now accepted as the first accurate model of DNA structure in the journal Nature. Experimental evidence for Watson and Crick's model were published in a series of five articles in the same issue of Nature. Of these, Franklin and Raymond Gosling's paper saw the publication of the X-ray diffraction image , which was key in Watson and Crick interpretation, as well as another article, co-authored by Maurice Wilkins and his colleagues. Franklin and Gosling's subsequent paper identified the distinctions between the A and B structures of the double helix in DNA. 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).

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". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson-Stahl experiment. 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. These findings represent the birth of molecular biology.

---

At first glance the discovery of NA could be attributed to Watson and Crick, they were the ones to receive the Nobel Prize, but the discovery of DNA actually was a series of discoveries. DNA was first observed by Friedrich Miescher, a Swiss doctor, who had isolated DNA from white blood cells in 1869. (ref) In 1928, Griffth identified a transforming principle (ref) By 1940, most scientists believed that DNA had a role in carrying genetic information but it was also believed that it had to be a protein, of greater complexity than the DNA molecule, that actually carried the information. In 1944, Avery, MacLeod, and McCarthy discovered that DNA prepared from one strain of pneumococcus could "transform" another strain. However, it still wasn't decided if protein contaminants were not responsible. (ref)

In 1950, Erwin Chargaff published a paper in which he described the equal ratios of adenine to thymine, as well as cytosine to guanine, something he found unusual, and which he called the complementary situation, but later was known as the Chargaff ratios This discovery would play a crucial role in determining the structure of DNA. (ref)

In 1952, it was reported that infection of Escherichia coli by T2 bacteriophages facilitated the entry of the DNA but left the protein coat behind, outside the host cell. This experiment provided the crucial evidence that it was DNA itself and not a protein that was the carrier of information. But the structure of DNA was still unknown. (ref)

It was known that water could be introduced into the DNA molecule. Rosalind Franklin, a x-ray crystallographic expert, working with Maurice Wilkins who provided her with the DNA, obtained a diffraction photograph which would reveal hints of the duplex structure of DNA. She maintained that the phosphates were on the outside.(ref) Linus Pauling, also was working on solving the structure, but his triple helix had the bases on the outside and the phosphates on the inside. This was found to be an impossible situation as the phosphates were negatively charged and would push themselves apart. A separate team, Watson and Crick, working closely together,(ref) unlike the Wilkins team, aware of Chargaff's work and Franklin's photograph, starting with cardboard models and found that by placing the molecules in a certain configuration, A & T and C & G looked the same.(ref) With the information based on the work of Rosalind Franklin and Erwin Chargaff, Watson and Crick discovered the structure of DNA on the morning of Feburary 28, 1953.(ref)

Ref http://www.dnai.org/index.htm

Thomas did you see the section above titled Do we want to axe the history section? If we do add this back I think that Griffiths and Avery should be mentioned too, especially since you talk about the confusion of whether protein or DNA was the genetic material. We probably need more sources here too, or at least more specific links to the CSHL web site. Chris Day (talk) 11:05, 5 March 2008 (CST)

I noticed after reading about history above that there is even more to the history than most accounts talk about. Each individual historical account appears as a partial listing. The website I listed above has actual interviews of (some) key players or comments by them about others. For example Franklin's grad student recalls how their group worked individually while Watson and crick worked together. In the end it was the work of all of them that enabled the final discovery to be made. I would like to continue to improve the history section as time permits and eventually use it as a start for a separate more detailed article on the history later on.

About the "Primer" aspect, I think a simple overview could be (re)written in the introduction section which already is one step in that direction. I have in the past found that an informative article for all levels can be written in four stages or levels. The first level is a single sentence (or two), the second level is a few paragraphs, the third level would be like an essay and the fourth level would be actual papers. While such a scheme would be difficult to use here, perhaps the scheme could be adopted in principle. The lead in would be level one, the overview would be level two, and the rest would be level three, while links to original references would take care of level four. I am not at all good at providing references as you probably noticed by now. Thomas Mandel 00:06, 6 March 2008 (CST)

feature to function

Thomas, you made an edit to call "complementary duplex structure" a function. Can we really call this a function? Is it not a property of DNA? Chris Day (talk) 23:27, 5 March 2008 (CST)

Hmmm, you may be right, I was trying to make my source's word "discovery" more informative. I made the changes and reworded the paragraph. Notice that we are well on our way tooward an comprehensive introductory paragraph. However, that last sentence or two seems to me to be details which are out of place in an introduction...

Thomas Mandel 00:16, 6 March 2008 (CST)

How many is scores?

My understanding is that a gene is comprised of at least three base-pairs because two base-pairs are not enough to code for 21 amino acids. I thought it would be informative to set the range of genes from the smallest to the largest. Now the smallest is written as "scores." I don't know how many "scores" is. Thomas Mandel 09:38, 6 March 2008 (CST)

I asked Google and the first four pages cames back with baseball scores. And this one "A film score is a broad term referring to the music in a film which is generally categorically separated from songs used within a film." It does not look like "scores" is a appropriate or useful term to use here. I wonder what the reasoning was to use it...Thomas Mandel 09:45, 6 March 2008 (CST)

Scores is in twenties. We could say tens. Chris Day (talk) 14:52, 6 March 2008 (CST)

I'm not sure I understnad your question here? You seem to be talking about codons not genes. A codon needs a minimum of three base pairs to code for 21 amino acids. But the context of the sentence is defintely talking about genes not codons. So tens or scores is appropriate. Does this make sense? Chris Day (talk) 14:52, 6 March 2008 (CST)

It is my mistake and lack of understanding. I am learning this as I write it, thank you for the correction. Thomas Mandel 21:04, 6 March 2008 (CST)

Sorry to quibble here but this edit introduces some problems. First, many genes have no codons (non coding RNA) and second, typically not all DNA in a genome is part of a gene (for example, telomeres and centromeres). I think you are writing here using information in the sense of the genetic code but as written it was referring to all information, including regulatory information, not just codons. If your goal is to focus on protein coding information I think this passage needs to be more specific. Chris Day (talk) 03:10, 7 March 2008 (CST)

Has this been fixed? Thomas Mandel 04:09, 9 March 2008 (CDT)

It depends whether you want to talk about genes or codons. I just rewrote it (amongst other changes) to be from a codon perspective. Chris Day (talk) 16:21, 9 March 2008 (CDT)

history preamble

I'm not sure if the preamble is a good fit here. Watson, Crick and Wilkins won the Nobel prize for "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material" not for the discovery of DNA. We need to reword this to say there is a history of active research on DNA prior to Watson and Crick but i don't think there can ever be a case for confusing their role as discovering DNA. And if this is a common misconception i don't think we should perpetrate this impression. I'll have a go at rewording it tomorrow if you don't beat me to it. Chris Day (talk) 03:47, 7 March 2008 (CST)

Yes, we should not perpetuate misconceptions. I was one of those that thought DNA was entirely discovered by Watson and Crick. It was a very slow process of learning bit bit that many others were involved. Indeed, it wasn't until now that I learned/realized what the Nobel Prize was specifically awarded for-- the discovery of the structure. And what they discovered could have been discovered by a kid playing with cardboard cutouts the shapes of which was determined for them. (That T&A and C&G had the same shape and could be stacked on top of each other) Thomas Mandel 19:29, 7 March 2008 (CST)

I think you overestimate what a child could do here. The key is a succinct and accurate description of the contributions from all players. To dwell on misconceptions takes it off message. Chris Day (talk) 23:06, 7 March 2008 (CST)

I was thinking about all the hard work accomplished by prior researchers, and how this inadvertantly escaped recognition due to the Nobel Prize. I listened to the words of Watson himself and how he described his Eureka moment which was brought about when he placed one cardboard cutout along side the complementary cutout. Assuming that the information needed to make the cardboard cutout was available to him, what he did was, in essense child's play. Again think of the research which led up to that moment the morning of the 28th of Feburary, 1953...I also read his book and it seems to me that the singular original event was that placing together of models. I don't mean to knock him, but how come everyone else has been forgotten? Just a thought. Thomas Mandel

Well I'd suggest the Nobel prize is always subjective. But given they can only give three prizes it is bound to happen. The list of those that should have been recognised is long. And everyone has a different list. Chris Day (talk) 08:08, 8 March 2008 (CST)

Well, basically I included all the old history with some minor changes. One major change is the inclusion of "In 1950, Erwin Chargaff published a paper in which he described the equal ratios of adenine to thymine, as well as cytosine to guanine, something he found unusual, and which he called the complementary situation, but later was known as the Chargaff ratios This discovery would play a crucial role in determining the structure of DNA. (ref)" which seemed to have been ommited. Yet it is this discovery that enabled Watson and Crick to make their cardboard models... Thomas Mandel

Agree this is critical and in fact this realisation was the key to Watson and Cricks success. Chris Day (talk) 23:06, 7 March 2008 (CST)

Can you come up withthe proper references? I got it from a website. Thomas Mandel

Might be tricky, for me it is common knowledge. I'll see what I can find. Chris Day (talk) 08:08, 8 March 2008 (CST)

Kornberg cites Chargaff, E. (1950) Experientio 6, 201 but doesn't say much about what for. Here is more --

Chargaff, E. 1950. Chemical specificity of nucleic acids and mechanism of their enzymic degradation. Experientia 6, 201-209.

Chargaff, E. 1951. Structure and function of nucleic acids as cell constituents. Fed. Proc. 10, 654-659.

Chargaff, E. 1963. Essays on Nucleic Acids. Elsevier, Amsterdam.

Chargaff, E. 1979. How genetics got a chemical education. Ann. N. Y. Acad. Sci. 325, 345-360.

Need proof for this one

"However, occasionally mistakes (called mutations) occur, contributing to the genetic variation that is the raw material for evolutionary change."

Not only is repair processes ommitted, this statement "the raw material for evolutionary change" begs for a proof. We are a huge mistake? Thomas Mandel

I'm not sure i understand your meaning of "we are a huge mistake"? I think your impliction is that mutations are all negative but that is not true since beneficial mutations do exist. Certainly DNA repair could be tied into such a section although that is a huge topic in it's own right. As are mutations. Chris Day (talk) 23:11, 7 March 2008 (CST)

Have you read Concepts of Symbiogenesis by Khakhina? Or The Symbiotic Planet by Lynn Margululis? Or The Symbiotic Universe by Greenstein? Basically what they are talking about is the integrative system ala Bertalanffy. In an integrative system, the elements, which are complementary elements, work together and through their interaction create a whole having properties not found in the separated elements. A whole greater than the sum of its parts. A simple example is the interaction of two gases which when integrated form the liquid we call water. Or rocket fuel depending on how the interaction is carried out. Kornberg writes that the entire DNA process is a complementary process (DNA Replication. Page 13). In fact this complementary process is carried out throughout the organism and it can be argued that the entire organism is a complementary integrative/differential system. So it isn't really impressive/useful to claim the alternative view of accidental formation, i.e., mutation, is the raw material of evolutionary change. Is there a definitive paper which proves mutation is the driver of evolution? We can avoid this problem simply by deleting that sentence which is really just an unproved assumption. later in the article cross over is discussed. That is more adequate. Thomas Mandel 03:00, 8 March 2008 (CST)

"accidental formation, i.e., mutation, is the raw material of evolutionary change" One minor tweek might be to say ""is a raw"" instead of "is the raw". I think there is plenty of evidence that can show this is a fact not a claim. There are non random elements to mutation but the vast majority are random with respect to the bigger picture of which genes get mutated. Let's avoid the problem for now, moving into sytems type stuff is beyond the scope of the article at this point. We can always revisit. Chris Day (talk) 08:14, 8 March 2008 (CST)

"is a raw" makes sense. Keep in mind that DNA is a complementary system, systems type stuff is fundamental to a complementary system. Thomas Mandel 18:18, 8 March 2008 (CST)

I was able to include the repair aspect albeit very briefly and in the process mention mutation and evolution too. There seems to be a tremendous variety of repair processes going on, and maybe this is something needing elaboration at some appropriate point in the article. I don't know enough to tell what is important and what is trivial. Do they still think that aging is accumulation of damaged DNA?

Is it OK to do some minor wording improvements

I'd like to go thru the first two sections and make the narrative (hopefully) flow more naturally, no content changes. Not if it gets in anyone's way, tho.

I'll be bold and go ahead, i welcome feedback and won't be offended in the least if someone reverts. Christopher J. Reiss 12:39, 8 March 2008 (CST)

please don't be afraid, thanks for being so considerate of others, but we all want this article to evolve so your input, and everyone's, is more than welcome. Just go ahead, lets see if we cant make a good article great.Gareth Leng 13:08, 8 March 2008 (CST)

reworded the first paragraph

Is this a net improvement? I was aiming to improve the 'narrative voice', and to lure the reader into the rest of the article. How'd I do? (I'm a newb, so feedback most welcome.) Is it mostly better (worth retaining the edit)?

Before

Deoxyribonucleic acid (DNA) is a very large biological molecule found in almost every cell and is responsible for providing information required for the development and reproduction of living things. Every living organism has its own unique DNA sequence (code) similar to a 'barcode' or 'fingerprint'. This code, called a genome, is used primarily to control the synthesis of proteins. The important genetic discoveries in DNA research are the complementary duplex structure, often referred to as the "double-helix", that enables the accurate replication of DNA in living organisms, and that the internally coded, inheritible information defines the genotype which provides the necessary instructions to produce the phenotype, or outward physical manifestation an organism.

After

Deoxyribonucleic acid (DNA) is a long helix-shaped molecule that carries the genetic code in all forms of life. The genetic code (or genome) is the 'blueprint' for all living organisms that contains all the information needed by cells to assemble a (nearly) exact duplicate. For instance, identical twins and clones have the same genetic code. Similar to a computer code, the genetic code is binary. The helix resembles a spiral staircase, where each 'step' is another bit in the sequence. One of the many remarkable properties of DNA is that it can self-replicate. Under proper conditions, if the two long chains of the helix are pulled apart, each strand will reassemble its missing partner so that two intact DNA helixes result. Aside from self-replication, the code sequence sets in motion an incredibly complex chain of reactions which directs the reproduction of the entire organism. It was a surprise to some that the genetic code would be found in such a simple and aethetically satisfying shape. The discovery of the helix in 1952 sparked a scientific revolution in molecular biology and genetic engineering. Research into the complex functioning of DNA during reproduction is still active.

Funny, I just spent two weeks carefully changing the intro around and instead of working with it, it just disappears Thomas Mandel 17:32, 8 March 2008 (CST)

You have indeed changed all the content. DNA is a double helix. "Blueprint" was discussed and rejected above I think. Replication is not a "nearly" duplicate. The genetic code is complementary not binary. If you pull dna apart it will tangle - try it, it must be disassembled section by section first. , Partner does not imply complementary. The chain of reactions does not reproduce the entire organism. The scientific revolution started well before 1952. It is true the research is still active. This sounds like Wikipedia text. Thomas Mandel 17:49, 8 March 2008 (CST)

Apologies to all, I tried to make a quick improvement. I find the tone to be stilted, which seemed out of place for the 'secret of life'. Subjective. (It wasn't WP text, i was composing on the fly.) I see the article is in capable hands already and beg pardon for my newbish intrusion ... Christopher J. Reiss 03:24, 9 March 2008 (CDT)

The point is thoroughly moot but it seems Thomas registered a set of objections rather hastily. A double helix is also a helix. Replication produces a near duplicate because environmental factors come into play (twins have differing fingerprints.) The code is binary *and* complementary. Complementary means partner. Peel the chains apart was a metaphor, fair correction. The rest of the text is similarly defended.

I point this out not as a matter of rebuttal, but merely to point out I made an effort to get it right (and didn't clip it from WP.) New articles beckon, be well CZ-endians

 updated Christopher J. Reiss 05:12, 9 March 2008 (CDT)

Suggestion

May I make a small suggestion here? Christopher, you are (rightly) concerned with trying to make an article that is very readable, and will be interesting to someone who comes new to the topic with little understanding - a "student level" version in fact. That's great, we definitely want those for Cotizendium. There is a danger though, in that some terms have very specific meaning for specialists, and it can be hard, as we see above, to satisfy both specialists and lay readers, and especially hard if it's done sentence by sentence. What I'd suggest Christopher, (if you're keen on pursuing this), is that we start a new subpage that is a "student level" version of the topic, where you and others can work up a separate clear language version for lay readers, and when its done then we can take a look at the whole thing. I liked your text Christopher, in that I saw what you were trying to do and liked it. Yes, it's not quite right, but it could be put right while keeping your intent. But the best place is in a subpage? Any other opinions?Gareth Leng 07:10, 9 March 2008 (CDT)

I appreciate Chris's intent, I am trying to the same thing. It is not easy, I spent four years in a college and a University working on the school newspaper instead of my classes, and still I am learning how to write well. During that process, and while working on a primer for a systems website, I found that most technical writing is written for the colleagues of the writer. PhD's are trained to write technical books. So what is the difference? Detail. Most papers and books written by experts seem to me to be written backwards. First the evidence is presented, then. at the end, the conclusions are presented. We read Tacho Brahe's calculations then we read Galileo... This led me to read a book from the back toward the front. Try it! (If I were writing this for a paper I would end up reversing almost all the text from back to front) After all those years, I have a plan. I found a way to write for the casual observer and the specialist. Geared toward hyperlinked text, my plan involves four phases. Phase one is a single sentence explaining the concept in very general (but correct) terms. This single sentence is there to catch the attention of the reader. If he is interested, then the link proceeds to the second phase which is a paragraph or two elaboration of the first sentence. Again it must be general and correct. IF there is errors, the specialist will not bother to read any further, while the casual observer is well on his way toward confusion. Phase three is an essay. Here we have a very few pages of elaboration and the introduction of some technical examples. Again the data must be correct. Phase four, if the reader has gotten this far, is a technical paper written by primary sources. Now, I too find considerable resentment toward "jargon". Toward a resolution of that problem I invented what I call "sympology" that which is stated in the simplest terms. Mathematics is like this. So the solution to "jargon" is not to eliminate it, but to define it. It is best if we use self-defining words when we can. But whenever a technical terms is used, the first time should include a definition. One or two words often do a good job. OK, enter the DNA article. To begin with, a lot of people already spent a good deal of time working on the article. I know the feeling when someone new comes in and deletes all that work. So I have attempted here to use the original text, opting instead to moving it around. I did not want to rewrite the article according to my plan, so I am trying to adapt it. Specifically, the first few sentences will be a very general and simple introduction. This part is very important. Then, I will move to the overview, where the first paragraph is essentially repeated but in greater detail. I don't know if I can succeed adapting the rest of the article to a phase three level "essay", perhaps it is there already. Phase four is already in place, at least in terms of links to original data. So Chris, my point is that, well, I spent two weeks reading original texts on DNA in order to write that first paragraph. I don't think it is complete, I have a lot more to learn. I must say that however it is written it must ot be misleading. I do not want to debate you, but I have never seen the word "helix" used to describe what is always described as a double-helix. Right from the beginning there is a "stop".Do you see my point? You may be correct about "stilted" but I am constantly looking at that paragraph trying to find a way to improve it without being inconsiderate of previous authors, who are, obviously, very competent. The only serious "errors" I have found is such things as a temporary removal of the history which wasn't replaced, omission of DNA repair, and in general misplacement of sentences which would read better at the beginning of the paragraph instead of the end. There's that writing backwards thing again. I would like to suggest that writing a simple explanation is much more difficult than writing a complex explanation. I notice that you work with computers, perhaps you could start with writing an article on computers just to get a feel of what it is like to work here. This is not at all like Wikipedia. To begin with, you can assume that the previous authors actually work in the field they are writing about. Writers like you and I are the exception here. Thomas Mandel 13:07, 9 March 2008 (CDT)

Good suggestion, Gareth. Just now I've got other articles to work on but will try to return and consider this option. I suppose this begs the larger question of the expected audience, which is a persistent and open question on which reasonable ppl differ.

I can imagine the expert/student type of fork would be a really cool thing for every technical subject, and would keep authors with differing emphases out of each other's hair.

I'm focussing on blank areas of CZ for now, so don't know when i'll get back here, but my Talk is always open ... (it's a very good article, btw) (updated) Christopher J. Reiss 12:29, 9 March 2008 (CDT)

How does ten million twists unwind?

Just read Cricks account of his discovery written just as they figured out the structure. One of his big questions then was how does the estimated ten million twists unwind? I recall reading that the DNA is sectioned, unwound, then put back together. Thomas Mandel 19:46, 9 March 2008 (CDT)

Combination of two enzymes. A helicase unwinds it as it seperates the DNA into two single strand reading for replication or transcription.

"The DNA to be copied enters the whirling blue molecular machine, called helicase, which spins it as fast as a jet engine as it unwinds the double helix into two strands."

But unwinding leads to supercoilng, so unwinding is only half the solution. The supercoiling is relieved by a DNA gyrase (aka topisomerase) that cuts the DNA to relieve the torsion then ligates it back together.

I do like the idea of presenting some of the biological problems such as "how do we unwind the DNA"? It is thought provoking. Thinking along the lines of the jet engine imagery above, "how fast can DNA be replicated" is also and interesting question. Bacteria can copy their DNA in less than 20 minutes. This might lead to the consideration of "how is it possible to replicate a larger genome" in a sensible timeframe (answer multiple origins of replication). Chris Day (talk) 22:37, 9 March 2008 (CDT)

Well, I spent the entire evening reading two huge texts, and at the end found myself in a forest looking for what I did not even know. There was no heading "Here is how it unwinds" Then I come here and here it all is! I almost know the answers to your questions, just kidding. I recall reading somehwere that DNA effectively unwinds at 10,000 RPM...But that isn't nearly as amazing as the process neurotransmitters goes through each time a neuron "fires". like from factory to fedEx to recycle plant all in millisecnds...PS I did suspect topoisomerases,,,Thomas Mandel 00:57, 10 March 2008 (CDT)

Huh?

Where did this come from?

...and in theory the cell ends up with a perfect copy of its DNA. Replication rarely achieves a perfect copy but a diverse set of repair mechanisms are available to the cell to correct the mistakes. Nevertheless some mutations will persist and in rare instances the mutation may alter function contributing to selective advantage for evoluti..."

I read that there are some sequences which have a error of one in two hundred thousand years.

OK, found it, One error in 10,000,000,000 replications. That should read rarely does not achieve a perfect copyThomas Mandel 00:05, 11 March 2008 (CDT)

Changed it to read --"In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA. Replication error is estimated to be one error in 10,000,000,000 replications. But, environmental factors such as heat can produce hundreds of mistakes in a day. A diverse set of more than 50 repair mechanisms are available to the cell to correct the mistakes. Nevertheless some mutations will persist and in rare instances the mutation may alter function contributing to selective advantage for evolution."

I think this would be called a bold edit. Please proof my corrections, Thomas Mandel

How do you define replications in the context of "10,000,000,000 replications"? Is it per base? I'll have to check to see what 5-6 mutations per generation equates to under normal conditions. Also I'm not sure if there are as many as 50 repair mechanisms, I'll look into that figure. Chris Day (talk) 02:00, 11 March 2008 (CDT)

Just to get us on the same page. The error rate of repliction is quite high for a first pass. However, after proof reading the error rate is dramatically reduced. It depends on whether you consider proof reading repair or not. On average there are 5-6 new mutations in the genome per generation for humans. Chris Day (talk) 01:52, 11 March 2008 (CDT)

THe book says fidelity depends on proofreading...Thomas Mandel

See cite I mention below, but in short 10^-8 error rate prior to proof reading 10^-10, as you cite above, post proof reading. Chris Day (talk) 12:43, 11 March 2008 (CDT)

OK have done some more research for the number of heritable mutations per generation. Assume human genome is roughly 10⁹ bases. Error rate is about 10^-10. So have roughly 1 error after a cell has replicate 3 times. To get a female egg is about 30 divisions (10 errors) to get a human sperm is more than 100 (~33 errors). So my estimate of new mutations per generation is too low (foggy memory I guess). Given the human genome is actually larger than 10⁹ and no environmental mutations have been considered, there could be a couple of hundred new mutations per human generation. Chris Day (talk) 12:52, 11 March 2008 (CDT)

recent edits

Do you think we need to be so specific with regard to the number of proteins in the opening paragraph? It seems to getting away from the subject?

The clone comment does not seem appropriate for the introduction since clones are barely mentioned in the article (only in a molecular biology context). Even if we add a new section on organismal cloning that sentence seems to be out of place. The connection with replication is not made clear. I would have thought that cloning would be more intuitive when thinking about genomes. Chris Day (talk) 02:12, 11 March 2008 (CDT)

There is so much information it become difficult to figure out what is important especially at the very beginning. Especially for a varied audience. I'll look at these edits tonight again. I really don't know what I am talking about but one sneaky trick I found useful to to make a claim and then wait to see if someone objects. For example, the error rate is not made clear in the texts I have but what I wrote about that may or may not be the true error rate. It did come from the book. The way it was written, "replication is rarely correct" scares me. And the impression I got from the book is that replication itself is always correct, but mistakes happen alll the time due to external effects. There is a big difference. Ah, yes, it doea imply after proof reading...

Again, what I am reading now is beyond me, that is, don't know enough about the facts I find to put them into context. I know you are there to catch me when I fall, so at least last night I found it better for me to throw in the kitchen sink and see what you throw back. Thomas Mandel 08:29, 11 March 2008 (CDT)

Replication is not always correct due to tautomeric shifts in the bases. For example thymine comes in two forms, keto and enol, the latter pairs with adenine but the latter pairs with guanine. It is, however, far more correct than I gave it credit for. Here are the numbers from Tago,Y., Imai,M., Ihara,M., Atofuji,H., Nagata,Y., and Yamamoto,K. (2005) Escherichia coli mutator Delta polA is defective in base mismatch correction: The nature of in vivo DNA replication errors. J. Mol. Biol. 351:299-308. An error rate of 10^-8 of which 1 in a hundred are not repaired. Therefore, total error rate of 10^-10. I guess my point was that replication is a hundred times more error prone than would appear from the final product. Chris Day (talk) 12:29, 11 March 2008 (CDT)

A useful number I have seen is that every cell in the human body has 10,000 mutations a day, not from replication, but from oxidative stress and ingestion of carcinogens, like benzo[a]pyrene diol-epoxides from smoking or grilled meat. The cell effectively fixes each of these every day will no ill effects. David E. Volk 10:31, 11 March 2008 (CDT)

Finished with first paragraph

I have done as much as I can do with the first paragraph. I think it presents a good introduction and is readable. I would like to hear some feedback or suggestions

I think the second paragraph needs a lot of work, my idea is to extend the first by including more detail about what is important about DNA. For example I have an old book by Asimov in which he sates that Avery's discovery was the most important discovery of all time. I will try to work on this one.

I made some minor changes to the third paragraph. My thinking is that it should be techinical yet tell the whole story, an advanced version of paragraph one. Paragra[h three seems now to be about external relatioships of DNA, so three and four would be internal/external relationships of DNA.

From there we go back to the history. Which now appears to be a technical version of paragraph two. I think we need an introduction to the history, something about how long it has been researched and the difficulties incountered. I personally like the history aspect because it explains how something was discovered.

The following paragraphs go into great detail. I had moved replication up in front of genes previously because the genes section was very technical. However, I notice that there is little or nothing about DNA repair. That DNA has to and can be repaired is new to me. I do have a text which describes the process in great detail.

I haven't read much beyond this point. but if previous writing is typical I would say that any changes would be merely moving stuff into better locations.

I have to say that it took me years to find out about chromosomes, that each chromosome is a single DNA molecule. Seems that most accounts lead one to think there is only one DNA molecule. Of course it is covered in a textbook, but most of my previous reading was articles.

Finally, I still have not found out what and how an organ is formed. DNA seems to produce amino acids, amino acids form proteins, so what tells the proteins where to go? And how they should assemble themselves? And how one hand/eye/ear/etc is identical too the other side?

But for now, how does the first paragraph look? ...said Thomas Mandel (talk) (Please sign your talk page posts by simply adding four tildes, ~~~~.)

Hi Tom, I made a slight change on the last sentence of the first paragraph. I don't think it changed your meaning, but check it and make sure. Feel free to revert. --D. Matt Innis 12:31, 13 March 2008 (CDT)

Much better, thanksThomas Mandel 23:57, 13 March 2008 (CDT)

I can see how editing an article such as this one could be a valuable educational tool. For one, I am constantly rereading over and over... Thomas Mandel 09:26, 16 March 2008 (CDT)

one molecule

My text says that the evidence indicates the DNA in a chromosome is a single molecule. No time now to review, will look into it later. Thomas Mandel 08:54, 22 March 2008 (CDT)

Your text must be defining DNA as being double stranded. I would dispute that definition from a chemical perspective although it may well be the working usage in the biology field, but I think it is more slang than accurate. Biologists do distinguish between single stranded and double stranded DNA (ssDNA vs dsDNA) which makes me think it is wrong from a biological perspective too. Regardless, a chromosome has a variable number of molecules. The useful unit for such a statement is chomatid not chromosome. Chris Day (talk) 09:02, 22 March 2008 (CDT)

Let's skip that for now. But isn't a single strand a single molecule and isn't a double strand a single molecule too? I'm wondering however if this is at all important, given the many ways of interpreting it...Thomas Mandel 23:46, 25 March 2008 (CDT)

From a protein perspective it is quite common to have mulitple proteins make up one enzyme, structure or transcription factor. The individual proteins are termed subunits and the group is often referred to as a complex. When the structure is very large the term used is supramolecular. When smaller, just two molecules, a term like dimer is used to distinguish there are two (or duplex in the case of DNA). For me, the phrase a "single molecule" implies one entity, one polynucleotide or one polypeptide. I think to say "single molecule" can only lead to confusion, possibly "one molecule of DNA" would be less confusing? I know it's a subtle difference but I think that would represent more common usage.

But bear in mind the usage of chromosome itself leads to confusion. The metaphase chromosomes seen in karyotypes have two molecules compared to the uncondensed chromosomes after mitosis. Chris Day 07:29, 26 March 2008 (CDT)

Footnotes

There are a handful of illformatted or footnotes that don't have references, just placeholder text. --Robert W King 13:15, 31 March 2008 (CDT)

I noticed that too, we need to go through and clean up the loose ends. I have made a start. Will come back and look through again. Chris Day 13:26, 31 March 2008 (CDT)

Ordering sections

Thomas, what is your logic for having Quadruplex structures as a subset of gene expression? I don't see the connection, especially compared to its previous location of alternative conformations.

Also, why do you think it's better to start off with the biochemistry associated with DNA prior to the structural chemistry of DNA? Especially given the structure is quite a natural progression from the history section which has a focus on structure. Chris Day 10:01, 1 April 2008 (CDT)

Examples of the two version and our current approved version for reference.

Version A	Version B	Approved
1 History of DNA 1.1 The genetic material 1.2 The double helix and code 1.3 The Human Genome Project	1 History of DNA 1.1 The genetic material 1.2 The double helix and code 1.3 The Human Genome Project
		1 Overview of biological functions 1.1 Genes 1.2 Genomes 1.3 Replication 1.4 Transcription and translation 1.5 Regulation of gene expression
	2 Physical and chemical properties 2.1 Base pairing 2.2 Sense and antisense 2.3 Supercoiling 2.4 Alternative conformations 2.4.1 A, B and Z forms 2.4.2 Quadruplex structures	2 Physical and chemical properties 2.1 Base pairing 2.2 Sense and antisense 2.3 Supercoiling 2.4 Alternative conformations 2.5 Quadruplex structures
	3 Functional modifications 3.1 DNA methylation 3.2 DNA-binding proteins	3 Chemical modifications 3.1 DNA methylation 3.2 Mutations
2 Biochemistry involving DNA 2.1 Replication 2.2 Helicases 2.3 Topoisomerases 2.4 Polymerases 2.5 Transcription 2.6 Translation 2.7 Nucleases and ligases 2.8 DNA Repair	4 Biochemistry involving DNA 4.1 Replication 4.2 Helicases 4.3 Topoisomerases 4.4 Polymerases 4.5 Transcription 4.6 Translation 4.7 Nucleases and ligases 4.8 DNA Repair	4 Interactions with proteins 4.1 DNA-binding proteins 4.2 DNA-modifying enzymes 4.2.1 Nucleases and ligases 4.2.2 Topoisomerases and helicases 4.2.3 Polymerases
3 Genes 3.1 Definition 3.2 Regulation of gene expression 3.2.1 Quadruplex structures 3.3 Mutations 3.4 Genomes	5 Genes 5.1 Definition 5.2 Regulation of gene expression 5.3 Mutations 5.4 Genomes
4 Genetic recombination	6 Genetic recombination	5 Genetic recombination
5 DNA and molecular evolution	7 DNA and molecular evolution	6 DNA and molecular evolution
6 Physical and chemical properties 6.1 Base pairing 6.2 Sense and antisense 6.3 Supercoiling 6.4 Alternative conformations 6.4.1 A, B and Z forms
7 Functional modifications 7.1 DNA methylation 7.2 DNA-binding proteins
8 Uses in technology 8.1 Forensics 8.2 Bioinformatics 8.3 Molecular cloning	8 Uses in technology 8.1 Forensics 8.2 Bioinformatics 8.3 Molecular cloning	7 Uses in technology 7.1 Forensics 7.2 Bioinformatics 7.3 Molecular cloning
9 References	9 References	8 References