Talk:DNA

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 (current)	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 Biochemistry involving DNA 2.1 Base pairing 2.2 Sense and antisense 2.3 Supercoiling (continued below)	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
2.4 Replication 2.5 Helicases 2.6 Topoisomerases 2.7 Polymerases 2.8 Transcription 2.9 Translation 2.10 Nucleases and ligases 2.11 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 Alternative conformations 6.1.1 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

OK I just rearranged every thing again, bear with me, there might be some method to my madness :) Part of my goal is to get some themes to build the text around and themes that are not so dry. I don't envisage that the text will change too much, certainly not the intro, but I want to work on the preamble for each section and linking ideas between sections. Chris Day 21:32, 1 April 2008 (CDT)

Who is this article for?

Guys'n'gals, this is a wonderful article - for someone who has had either AP biology, or has read a lot of popular science in the biology area, or something like that. For an accountant, or a high-school art major, or a ballet dancer, this is way too much too fast. By the time you get to enabling the transfer of information from a series of genes within the DNA molecule to a ribosome, a biochemical machine that translates the code and assembles a protein molecule from amino acid you're losing them - and that's in the first paragraph!

Go slower - a lot slower - use more analogies (talk about how the DNA is basically a blueprint which is used to create all the complex molecules and structures needed to build the chemicals used in cellular mechanisms, cells, organs and organisms - i.e. the various levels of abstraction in a living being), explain the things you are introducing more (what's a protein, what's an amino acid), yadda-yadda.

Don't get me wrong, I think we have a place for material like this too, and think we ought to have it, in /Advanced articles - but this is a general encyclopaedia, for use by the general public - and most of them will find this too advanced for them, at least if they come here looking for intro material on DNA. The article a college biology major will find interesting and useful (this one) is not the article a high-school art major will find useful. J. Noel Chiappa 00:29, 2 April 2008 (CDT)

This all goes back to who is our audience. I agree this is too high for university but it just needs pruning here and there. Unless of course we're not aiming for university level? Then we need more analogies. See the student level section i started with an analogy. I was going to work that up into a high school level type article. Now we have the advanced subpages that opens up a whole new angle too. In fact it was the latter that inspired the more casual headings since i know there is a place for the advanced stuff to migrate too. Lets see how this develops. Your eyes will be helpful Noel and thanks for any input in advance. Chris Day 00:46, 2 April 2008 (CDT)

Well, that is the $64x10^9 question, right? Has the question of who our 'base' articles are for ever been definitively settled? I suppose one could go two ways: 'base' is in the middle, and 'student level' is more of a beginner thing; or you could say 'base' is 'basic', and we go up from there. As long as things are clearly marked, and it's easy to get back and forth, I guess it shouldn't make a big difference. However, I suspect our users might find the latter option the most natural (and it might also be seen as less elitist). If this question hasn't been settled on a project-wide basis, I think it should be - and soon, obviously! J. Noel Chiappa 01:09, 2 April 2008 (CDT)

Here's the problem. The average audience will vary dramatically depending on the topic or article. What is right for DNA will be wrong for other articles. So it is hard to set a level that suits every case. Not to mention it is hard for any given author to write at the same level on a breadth of topics. As a result this also means we all have a different opinion of what "entry" level is, or "university" level. No surprise here, of course, since the is no real objective measure of level, hence, all the discussion this generates. Chris Day 01:25, 2 April 2008 (CDT)

As I said on the forums, I think the appropriate level will depend on the article. But DNA is something you can expect a very wide range of people to look at, and for article which can expect such a wide range of readers, I think we need to shoot for 'moderately intelliegent teenager' in the main page (subpages can contain much considerably more advanced stuff). J. Noel Chiappa 16:52, 2 April 2008 (CDT)

There is far too much information in this article in my opinion, leading one to have to read quite a ways down to see what DNA actually is, a string of bases attached to ribose sugars, connected by phosphates, and H-bonded across the strand. Many of the small paragraphs, like:

• Helicases
• Topoisomerases
• Polymerases
• DNA transcription
• Translation
• Gene Expression
• Nucleases and Ligases
• DNA repair
• Bioinformatics

should not really be explained in this article, but exist in separate articles and be only links here, somehow used in a sentence, like; the expression of genes in DNA requires enzymes like helicases and polymerases to provide mRNA, which is then used in ribosomes to produce proteins. That is fairly to the point regarding DNA's role.

Much of the material presented here should be in Gene or Gene expression, DNA repair, Chromatin and so on. David E. Volk 16:35, 2 April 2008 (CDT)

Yes, agree completely. Great material - wrong place. J. Noel Chiappa 16:52, 2 April 2008 (CDT)

What we are about to see is the evolution from a wikipdia article to a citizendium article. The current approved version is not that different to the wikipedia article. And think of all the stubs we have in here alone. :) Chris Day 17:51, 2 April 2008 (CDT)

I disagree with David and Noel. Why would "translation" be explained elsewhere when it is one of the two purposes of DNA to begin with? And if you remove helicases you take away how it works. The problem is not us, it is scientists who feel the need to create large words. A phrase like "the expression of genes in DNA requires enzymes like helicases and polymerases to provide mRNA, which is then used in ribosomes to produce proteins." may sound simple but it is is not at all explanatory to someone who does know what these terms mean. And the terminology/phrasing is misleading, ribosome does not produce, it assembles, and the mRNA is not used in the ribosome, it is used by the ribosome. The entire sentence as written is, frankly, "wrong."

And where else would one see DNA info but in the DNA article? Would one have to read fifty articles and then piece the material together and then realize what it all means as a whole? Simple writing does not mean reducing the quantity of words, it means using the words in a very hard to achieve wise way.

The best way to solve this problem is with hyperlinks. A glossary. A Glossary can be a very useful tool here. A new word should be defined at the first instance, and it should then be linked to a detailed definition/explanation. A reader should be able to work his way through an article, perhaps slowly, and arrive at a place of great knowledge. IF there is a need for a "simple" explanation of DNA, then we should follow Gareths proposal and specifically create a "simple" and separate article. But I question the notion of "typical teenager level" A typical teenager wouldn't bother going here, he or she would go to Wikipedia.

We tout the role of "expert" here, shouldn't we be writing articles that look like they have been written by an expert? If indeed we are experts, then we ought to be finding ways we can write for all levels rather then dumbing down an article for a supposed uninformed audience.

There is a way to do that. In my work I have tried to write at four levels. Level one is a "simple" (but accurate) single sentence definition/explanation. Level two would be a paragraph. Level three would be an essay. Level four would be a technical paper. So it would look like, at level one, a glossory, and each term would link to a elaboration in level two. Level three is much like an essay. And then level four is a primary paper written by a practioner in the field.

It is possible to write one article which has all four levels in it. And that is why we need to go deep into the article before we get to more details. In other words any reader should be able to read as far into the article as he can/wants, confident that the information he or she already covered is accurate. So a typical teenager, whatever that is, might read only the first paragraph, but a PhD in a different field might choose to read the entire article. Writing an article this way would require the author(s) to know what they are talking about.

I would like to point out that I think Chris Day is right, this article has evolved from a wikipedia article to a citizendium article, I hope we don't destroy it. It would be far more useful if breaks or jumps in the flow were pointed out. Thomas Mandel 10:45, 3 April 2008 (CDT)

Re: translation and the ribosome, "produce" is just less specific than "assemble". It is not wrong unless you use a more specific definition of produce?

As far as non-involved editors commenting here, that is the crux to a good article, as the writers become far to close and usually cannot see the wood for the trees. I do think the four less approach you advocate is a good tool and something we probably all do unconsciously. I often wrestle with the problem of whether to define simple yet technical terms such as protein and gene. To an extreme it makes the writing hard to read. A glossary is effectively what the related articles can be used for although this relies on the reader being conscientious are flipping to the related article page (not developed here I might point out but see Biology/Related Articles). Another option is popups but I wonder if that is more problematic and too technical to be useful for all. Chris Day 11:31, 3 April 2008 (CDT)

Much of what you say (such as how you can write an article that any one can read) I agree with.

However...

If the typical teenager, etc isn't coming here (eventually - right now we're not well known, populated with content, etc), we might as well shut down the project and all go home now.

THIS IS INTENDED TO BE PRIMARILY A GENERAL ENCYCLOPAEDIA, FOR THE GENERAL POPULATION. Think the 11th-13th edition Britannica, but on the WWW.

And may I remind you that the BBC reporter looked at an article on an advanced topic at both Wikipedia and here, and found both articles similary incomprehensible to him! (So much for the 'dumb people' being able to rely on Wikipedia.) We need to do a lot better than that.

I disagree completely when you say "a typical teenager .. might read only the first paragraph, but a PhD in a different field might choose to read the entire article". It is perfectly possible to write a lengthy article, on a complex topic, one that covers a lot of ground (because such topics inherently have a lot of ground to cover) - but do it in a way that an average person can read - and understand - the entire article. People who write popular science books do this all the time - and they sell lots of copies to ordinary people.

I will happily become involved - and help rewrite the entire article from top to bottom if need be. J. Noel Chiappa 21:30, 3 April 2008 (CDT)

Rather than tear down everything that I and the others have "assembled" why don't you start and write that popularized version of DNA as a separate article? I would like to see how you do that. That way both of us can work here instead of just you. What I meant was that the typical teenager most likely is not interested in all the greater detail that DNA entails, whereas the PhD would be interested. The teenager probably wants it "quick" But if the teenager is interested then the detail should be there for him to find. My point was that the first paragraph or introduction should be a complete story, such that a general reader would be able to comprehend it and hear the whole story. Does it do that? And then the story could start all over, but with greater detail. And then after the detail has been comprehended, the reader would be able to comprehend even more. And, in principle, by the time the reader reaches the ending, he will have a much greater understanding than any popularized version. Think of it as "growing up". At least that is what I am trying to do. I know it can be done because I learned calculus that way, not from the 19 texts a professor gave me, but from a small programmed text. But I respect the work of those who came before me, and instead of rewriting them I am satisfied with just rearranging what they did. I didn't know this was supposed to be a general encyclopedia, I thought it was supposed to be a compendium that is obviously written with expert guidance. For example produce and assemble. Both words can be understood by a general reader, but technically the DNA process does not produce proteins, it assembles them from amino acids. I don't know about a BBC reporter or the articles he couldn't understand. What is that about? To tell you the truth, when I started editing this article I had no idea what DNA was. I had to learn all this bit by bit. And it took weeks, months. And basically what I did is not change the content but change the sequence so that one thing led to the next thing. It might not be there yet, but that is what I am trying to do. And I am ever so grateful to the editors here who have allowed me to do my thing to their article. That is what I meant by being involved, been through the wringer is the popular way of saying it. Thomas Mandel 00:12, 4 April 2008 (CDT)

PS'' "On the contrary, for ourselves, for the general public, what we require is to get more fully and precisely into the proper language of genetics."'' Horace Freeland Judson "Talking about the genome" Nature 409: 769, 15 Feb. 2001

intelligent design......

....seems a little out of left field. If we are going to push this back to origin of life then the more pertinent discussion would be which came first, DNA or protein, and the RNA world hypothesis. But that is far from the topic of DNA the molecule and its role in biology. Chris Day 18:03, 2 April 2008 (CDT)

I think that it is right to raise these issues here (and also to mention the intelligent design controversy in passing). I think this article will need a simplified student level version, but generally I like the way its going. I agree that some of the subheadings could be dropped however (moved to new stubs?). I modified the opening reference to barcode etc - it's a bit misleading to draw that analogy. Be careful about details, the opening mentions DNA in every cell but later it is acknowledged that red blood cells lack it. The text seems to imply that cell types express unique proteins - they don't, cell types express a unique combination of proteins, a unique subset of those encoded.Gareth Leng 03:35, 3 April 2008 (CDT)

I only included this because in reality there is a dispute with the preceding paragraph which appears to say that random mutations are wholy responsible for evolution. I personally find this ironic, because today we call random mutations "birth defects". Thomas Mandel 11:00, 3 April 2008 (CDT)

What about lactose persistence? Was that mutation a birth defect? ;) Hence, one of my titles being "the good, the bad and the ugly" (although here I was also thinking of recombination, re: good). A better title would actually be "the good, the neutral and the ugly". Chris Day

I wonder if it really is a good idea to bring the dispute into the article, but Larry wants neutrality and if the statement is made that evolution is random then the statement that evolution is not random also must be made. Keep in mind that Darwin's evolution applied to changes within a species and it was only later that others expanded it to everything else as well. I cringe when I read a scientist state that a particular organism exists because of "selection" and then walks off the stage as if he explained it all. That is no different in my mind than saying that God made it. I believe there is a natural explanation but random isn't it. The Universe is ordered right from the start. And this ordering is arguably based on "working together" i.e., complementarity. DNA is a proof of this. The only elements of the Universe that do not follow this scheme are politicians and stuff like cancer.

Some might jump in and ask about the tiger that eats the ox. Well, it is obvious that they are working together. Only some humans kill fo the fun of it. I find it interesting that the virus does not have a repair mechanism derived from complementarity. It can only change. Maybe the virus is life that could/did not "evolve" Maybe the virus is an example of what mutation can accomplish over the period of several billions years?Thomas Mandel 13:41, 3 April 2008 (CDT)

Natural selection is only one of many aspects of the theory of evolution. They are not synonymous. Another thing is that the randomness discussed is primarily from the perspective of alleles that are created. To generalise though is difficult because it depends what you mean by random. Thymidine dimers are a common result of UV mutagenesis. The chemistry is not random, it will only occur where two TT's are together. Nothing random about that. But which pair of T bases get mutated is random, how could it not be. Same with chemical mutagenesis, for EMS transition mutations are more likely (not random), but the loacation of the transitions in a chromosomal context is random. There is plenty of randomness in evolution. Genetic drift is random too, by definition.

I still stand by the fact that this is too much for this article. Far better to cut the problematic sentence than open up a whole debate. Literally every biology article could have this debate. The question is should they? I don't know the answer, and possibly this one should, I'll wait to hear what others think. Chris Day 13:46, 3 April 2008 (CDT)

The problem wouldn't be a probelm if the scientists would admit that they do not know. I agree with you, as usual, it would be far better to leave evolution out of it. Sometimes less really is better.Thomas Mandel

Don't confuse popular science, which is often simplified, with scientists (with respect to truth). Also, science is not about cataloging what we do not know, and there is plenty, but about testing hypotheses and building models to give the best representation of what is thought to be happening or has happened. Models are not presented as fact, except by the media. Chris Day 17:56, 3 April 2008 (CDT)

What I meant was that scientists ought to admit they do not know when they do not know. Far too often I have seen a theory turn into a fact by the time it gets to the man on the street. Perhaps this is a fault of the reporter but I don't see those scientissts correcting the reporter. Thomas Mandel 23:12, 3 April 2008 (CDT)

As I said science is all about what we don't know, they admit it all the time. May be I am misunderstanding your point here? In my experience reporters rarely get it right and extrapolate for sensation. I'm sure this is not just a problem for science. And scientists are so used to being misrepresented that it's no surprise when it happens. So few are bothered enough to jump up and object. In general the science in the New York Times is pretty accurate, they are the exception. Chris Day 00:07, 4 April 2008 (CDT)

Well, take the black hole for eaxmple. Recent news reports that an observed tremendous burst of outward flowing matter from an AGN proves that a black hole resides there. But if one digs deep into the theory, one finds that the person who actually is working on accretian disks states vbery clearly that his concept is the only mechanism they could think of that would result in outward flowing matter coming from a point that according to mainstream theory should be sucking matter in. So the black hole is speculation devised to explain an anomaly which would falsify a theory that supports thousands of scientists, professors and publishing houses if it wasn't explained away. So the hypothesis becomes a theory and that becomes a fact. When the fact is that they really do not KNOW. Thomas Mandel 00:42, 4 April 2008 (CDT)

<unindent (is that a word?)>I don't know anything about black holes, so I can't comment on the ideas. But, scientists rarely, if ever, use the word prove. Are you sure that is not a journalists interpretation? Or is that your point? If so, all I can say is that it happens all the time. No scientist would be surprised or bother to correct such articles, there are just too many of them out there. Chris Day 01:11, 4 April 2008 (CDT)

That's my point. The primary source says "assumption" and then "conjecture" And as it gets filtered down, it becomes "theory" then "proof" and finaly emerges as "fact." The entire big bang theory is based not on observations, but a single assumption (that red shift is a doppler effect) that Hubble denied to his dying day. Yet we often see "Hubble proved expansion" when really it was his colleagues who added "c" to his original equations. Amazing what a single letter can do....My point is that it is very important to say the correct thing, especially to the general public.

We agree. Chris Day 10:56, 4 April 2008 (CDT)

The introduction

Here is the whole story

Introduction

DNA (Deoxyribonucleic acid), is a very large biological molecule found in the nucleus of almost every cell. DNA is responsible for providing the genetic information necessary for the development and reproduction of all living organisms. Every living organism has its own unique DNA code which is stored in the DNA molecule as a sequence of very small pairs of molecules - much like a genetic 'barcode' or 'fingerprint'. As a process, DNA functions like a template, from which information is transfered from the sequenced genetic code within the DNA molecule, to an enzyme (a biochemical assembly machine) called a ribosome. The code is transcribed to a molecule called Messenger RNA (mRNA) and carried to the ribosome. The ribosome translates the code and assembles a protein molecule from amino acids (the building blocks of proteins) according to the code's sequence. Proteins are very complex molecules utilized for intercellular communication, regulation and construction.

While every cell containing DNA in any one organism has identical DNA, each different cell type will synthesize the proteins common to most cells, along with an unique organization of proteins that defines the specialized functions of that particular cell type.

The two strands of DNA are held together by hydrogen bonds between bases. The sugars in the backbone are shown in light blue. The complementary base pairs are red/yellow and blue/green.

Overview

In most organisms, DNA is structured as a very long and very narrow double-helix formation consisting of two DNA strands coiled around each other in a head-to-toe "antiparallel" orientation. The strands provide a structural support for a complementary pair of bases located inbetween the strands. A base is like a letter of a genetic word. A series of three base pairs forms a codon ( a DNA word) on the DNA strand that encodes the information for one amino acid residue. A series of codons, and associated start/stop codons, (a DNA sentence) form the genetic code for the selection of particular amino acids and their specific arrangement necessary for the assembly of a protein molecule. The protein molecules, as many as 20,000 different types, are used in the cell, or are transported to other areas of the organism.

Each single strand of DNA is a long biopolymer comprised of repeating units called nucleotides (a nucleotide is a base linked to a sugar and one or more phosphate groups) which form a sugar/phosphate backbone. Attached to each sugar molecule (deoxyribose) is one of four bases; Adenine (A), Thymine (T), Guanine (G) or Cytosine (C). Each base is a structural complement of its opposing base; adenine always pairs with thymine and guanine always pairs with cytosine. The complementary base pairs, A&T, C&G, are identical in size and shape and will fit between the backbones of double stranded DNA in only one of these four arrangements - TA, AT, GC and CG. The complementary strands are held together by hydrogen bonds between the bases. This complementarity, at work in all the DNA functions, makes it possible for DNA to be copied and repaired relatively easily, while accurately preserving its information content and thereby forms the basis of semi-conservative DNA replication.

Nuclear DNA is organized into chromosomes each containing many genes. a gene is...At conception, the male sperm and female ovum (an unfertilized egg) each contribute 23 chromosomes for a total of 46 chromosomes in the fertilized embryo. In eukaryotes (organisms such as plants, yeasts and animals whose cells have a nucleus) DNA is mostly stored inside the cell nucleus. Some organelles in eukaryotic cells (mitochondria and chloroplasts) have their own DNA with a similar organization to bacterial DNA. In prokaryote cells (organisms such as common bacteria), DNA is located in a region called the nucleoid. Viruses have a single type of nucleic acid, either DNA or RNA, directly encased in a protein coat called the capsid. Some cells, such as blood cells, do not have a nucleus and do not contain DNA.

The entire DNA sequence of genes in any organism is called its genome. The genome provides the necessary genetic instructions to produce the phenotype, the outward physical manifestation of an organism.

Thomas Mandel 13:24, 3 April 2008 (CDT)

genes

You ask "are codons a "primary" part of a gene?"

I would say no, except in a protein centric world. Many genes exist that have no codons, so I don't think you can ever consider codons primary in that context of a gene. Chris Day 13:42, 3 April 2008 (CDT)

So what is the name for a series of codons? Thomas Mandel 13:44, 3 April 2008 (CDT)

Open reading frame, or ORF. Chris Day 14:50, 3 April 2008 (CDT)

We have a problem. So far Asimov and the Utah center for genetics both say that it is the genes that contain the information. I also remember reading here that there are different definitions about what a gene should be defined as. I suspect that there is a missing word, a missing word that is key to understanding DNA. For example, in computer science, they write about Bits that make up a BYTE. But it isn't the Bits or the Byte that carries the information it is the "Bitting" and they don't have a name for it. Oh, they have a name, but something no one ever heard of. So the correct terminology would be the name of the relatinships of the codons. The codonings. Thomas Mandel 15:01, 3 April 2008 (CDT)

Just to complicate the issue, in eucaryotes ORF's do not exist in most genes (the DNA version) as it is usually broken up by introns. Only in the processed mRNA do you see the open reading frame. And here we venture into further discussion of "what is a gene" due to alternative splicing. Depending on the environment or cell type a transcript can be processed into different mRNA products. Thus, one transcript can produce different ORF's. So the old idea of one gene one protein, that was wrong dues to non coding RNA's is also wrong because one gene can produce multiple proteins. This is similar but different to operons. In this case the different ORF's from alternative splicing share many of the codons, but not all of them. It is hard to generalise when it comes to DNA and genetics.

Genes do contain information, Asimov and the Utah center are correct. Codons are not the only information in genes, they are one kind of infomation important for translation. Chris Day 14:50, 3 April 2008 (CDT)

Seems to me we have a context problem. So the answer would be to tag the word "gene" with the proper context. Within the context of a strand of DNA it would be dGene and within the context f a Chromosome it would be a cGene, something like thatThomas Mandel 15:07, 3 April 2008 (CDT)

So can you write a paper, get it published and find a reference to it before supper? Thomas Mandel

Alternatively, are you telling me that after all this research I have no idea what a gene really is? Does anyone? Thomas Mandel 15:12, 3 April 2008 (CDT)

I am trying to tell you that a gene is not just something that encodes a protein. Chris Day 15:14, 3 April 2008 (CDT)

I thought so. In this context I have no idea what a gene is. How deep would a reader have to go before he realized that there is more to a gene? Or has gene come to mean so much that it is a useless term? If it is a general term, then I like my idea of dGene and cGene. My question is now, can we, given a series of codons and associated start and stop codons which are known to result in a protein, call that a gene?Thomas Mandel 15:32, 3 April 2008 (CDT)

Gene is not a useless term unless you try to use it too specifically.

It is correct to say that:

Some genes have "a series of codons and associated start and stop codons which are known to result in a protein".

But it is incorrect to say that:

A gene is DNA that has "a series of codons and associated start and stop codons which are known to result in a protein".

Does this make sense? The first usage is a more general usage than the latter. The latter is too specific and wrong. You could even say "Most genes have a series of codons...." and be fine. May be this is semantics but it is very common to think that all genes encode proteins. It is important we do not give that impression. Chris Day 15:49, 3 April 2008 (CDT)

Here are the definitions (from genomicglossaries.com). No one knows what a gene is...yet. Thomas Mandel

I disagree, we know what a gene is, the small differences of opinion in the defintion are semantic compared to the overall concept. That people talk about genes in different contexts does not mean there are differences of opinion with regard to the question of "what is a gene?". What specific differences of opinion make you conclude we do not know what a gene is....yet? Chris Day 00:57, 4 April 2008 (CDT)

IT is a semantic "we don't know" until we all finally agree which we will never do because the work is multiordinal. The solution is simple - dGene for codons, eGene for more, cGene for overall, they do it with mRNA

As far as I can tell the only people worried about this are the bean counters that want to know how many genes there are in any given genome. Most biologist don't work with absolutes and are quite comfortable with definitions that are not definitive. In fact, historically biologists change definitons quite regularly. The important thing is to clarify usage within any given body of work. Other examples, "what is an exon?", "what is epigenetics?" or "what is life?". None have a definitive answer and its not that important with respect to understanding the overall concepts. Chris Day 01:43, 4 April 2008 (CDT)

"What is an enzyme?" and "What does 'level of gene expression' refer to?", "What is junk DNA?" or "What is a species". Chris Day 02:33, 4 April 2008 (CDT)

OK, so it is correct to say a series of codons is a gene. I think I see where I started to say the wrong thing. Genes encode proteins but not all genes encode protein. So a gene is a (any?)genetic unit of information. And the specific definition depends on where the gene is. Thomas Mandel 02:06, 4 April 2008 (CDT)

"a series of codons is a gene" is is not correct. A series of codons is part of a gene.

"Genes encode proteins but not all genes encode protein" Would be better as "Most genes encode proteins" because 'genes encode proteins' contradicts 'not all genes encode proteins'. That leads to confusion.

"So a gene is a (any?)genetic unit of information." No because a nucleotide is a genetic unit of information, a codon is a genetic unit of information too and they are not genes.

"And the specific definition depends on where the gene is." I'm not sure what you mean by this. If I understand you correctly the answer is no. A gene is a gene where ever it is on a chromosome. Chris Day 02:27, 4 April 2008 (CDT)

pulling out for reconsideration

Chris I pulled these three paragraphs out because they are way too detailed for now. Let's look at what happens without them and then decide later, ok?

Sense and antisense

A DNA sequence is a "sense" sequence if it is the same as that of a mRNA copy that is translated into protein. The sequence on the opposite strand is the "antisense" sequence. Sense and antisense sequences can co-exist on the same strand of DNA; in both prokaryotes and eukaryotes, antisense sequences are transcribed, and antisense RNAs might be involved in regulating gene expression.. (See Micro RNA, RNA interference, sRNA.)

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). In these cases, some DNA sequences encode one protein when read from 5′ to 3′ along one strand, and a different protein when read in the opposite direction (but still from 5′ to 3′) along the other strand. In bacteria, this overlap may be involved in regulating gene transcription, while in viruses, overlapping genes increase the information that can be encoded within the small viral genome. Another way of reducing genome size is seen in some viruses that contain linear or circular single-stranded DNA.

Supercoiling

DNA can be 'twisted' in a process called DNA supercoiling. In its "relaxed" state, a DNA strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted, the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix (positive supercoiling), and the bases are held more tightly together. If they are twisted in the opposite direction (negative supercoiling) the bases come apart more easily. Most DNA has slight negative supercoiling that is introduced by topoisomerases. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.

Alternative conformations

The conformation of a DNA molecule depends on its sequence, the amount and direction of supercoiling, chemical modifications of the bases, and also solution conditions, such as the concentration of metal ions. Accordingly, DNA can exist in several possible conformations, but only a few of these ("A-DNA", "B-DNA", and "Z-DNA") are thought to occur naturally. The "B" form is the most common. The "A" form is a wider right-handed spiral, with a shallow and wide minor groove and a narrower and deeper major groove; this form occurs in dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, as well as in enzyme-DNA complexes. Segments of DNA where the bases have been modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in regulating transcription.

Thomas Mandel 01:26, 4 April 2008 (CDT)

I agree, I think these are best seeded as stubs for new articles. I think we need to be clear that Citizendium articles can be pitched at different levels, and this article is fine as pitched at biology undergraduate level; we need a new lower level article as well, and the newly seeded articles may be pitched at a higher levelGareth Leng 04:48, 4 April 2008 (CDT)

Actually I had to move part of it back into the article.

As far as "lower level" what does that mean exactly? What is it about an article that would qualify it as "lower level" Do we really mean introductory level? If so, what is it about an introductory article that is "ordinary"? Does it mean that we need to recast the article into ordinary language? Can that be done? If it could be donw, why isn't it being done all the time? What level of expertise would it take to recast the technical into ordinary terms competantly? Or does it mean that we introduce the technical terms as they are used? Could it be that all we can do competantly is leave the great detail out? Thomas Mandel 21:15, 5 April 2008 (CDT)

Well, see Life and the draft of Life (student level). You/we don't need to do it, it would just be nice to have a simple version someday.Gareth Leng 10:54, 8 April 2008 (CDT)

PS

PS "On the contrary, for ourselves, for the general public, what we require is to get more fully and precisely into the proper language of genetics." Horace Freeland Judson "Talking about the genome" Nature 409: 769, 15 Feb. 2001

There is a quotation that I came across some time ago. "It is not so much where we are at, but rather in what direction we are headed." I do not support dumbing down this enclycopedia so that we would be accessible to "the typical teenager" And I question the notion that a DNA article should be written for the art majors. Does that mean the art articles are written for Biology majors? And exactly what is a "general audience"? Is an 80 yr old senior part of the general audience? I find such an attitude very distasteful, condescending and insulting to the general intelligence of our audience. I think it is a cop out, a futile attempt to shift the blame (and work) from the writer to the reader. After all, if we assume the audience is dumb, then we can get away with writing dumb articles. What if we carry that logic out to the extreme in all our articles? No way, what we need to as writers is try and try again to write well enough that we can reach all levels. A poor writer might assume that it would be easier to write a simple article. But a good writer knows full well that it is extremely difficult to write a good simple article. So I reject the idea that an article can be written incomprehensively, I think such an article actually is poorly written. Thomas Mandel 23:48, 5 April 2008 (CDT)

protein delivery

The protein molecules, as many as 20,000 different types, are used in the cell, or are transported to other areas of the organism by UPS same day delivery service.

I don't really know what you mean here? Are you talking about delivery within a cell or from cell to cell? Chris Day 00:01, 8 April 2008 (CDT)

It was only a joke. I find it amazing though, that the transfer of proteins is accomplished in many cases by packaging them into containers. Take the neurotransmitter in a nerve sell. I tis construted and placed into a vesicle and transported to the appropriate site.

i think the analogy was apt, but the context was a bit off. It seemed you were talking about intracellular movement but you were also talking about proteins moving to construct other organs. Chris Day 17:48, 8 April 2008 (CDT)

Mitochondrial DNA

I feel the statement about mDNA needs to be in the lede paragraph if the lede paragraph states in any way that DNA is unique in each individual, otherwise it continues the misguided notion people have that all DNA is unique. In any event, the article should start out by noting that there is more than one kind of DNA because many people do not know this. David E. Volk 10:14, 8 April 2008 (CDT)

While this information may be crucial, placing it into the lead paragraph is the introduction of detail that needs to be explained immediately. I have three texts I am working from and none of them mention mitochondiria in the introductions. I'll look into it though. Kornberg mentions mitochrondia first on page 601...Thomas Mandel 17:55, 8 April 2008 (CDT)

I'm not sure I know what you mean by "misguided notion that all DNA is unique"? What is the context for this misunderstanding as it sounds about right. If anything the mitochondirial DNA changes faster than the genome. Chris Day 10:20, 8 April 2008 (CDT)

That is my point exactly! Nuclear DNA is unique to each individual, but mitochondrial DNA is passed down directly from the mother as an exact copy. Thus, your mitochondrial DNA, unless damaged, is the same as your great-great-great-great.... grandmother, (on your mother's side of course).

Well, are there not sections of DNA that are not unique? Does that mean that DNA is therfore not unique? Are individuals unique? Thomas Mandel 17:55, 8 April 2008 (CDT)

Hence the news story a few years back about the "mitochondrial Eve".

Since this article is called DNA, not nuclear DNA, I think this point needs to be made in the intro where uniqueness and "bar"-code phrases are used. David E. Volk 10:25, 8 April 2008 (CDT)

Why does it have to be in the lead paragraph? If it is placed there, it confuses the reader because now there are two locations and two types and two histories. Certainly these points are inportant but why can't it be covered later after a general understanding is obtained? If it is introduced immediately, then all subsequent statements will have to follow the differention. I have crafted the first paragraph to tell the whole story with understanding as the goal. it is not good to include detail at the expense of understanding. Thomas Mandel 17:55, 8 April 2008 (CDT)

I almost never do this, but reluctantly, here is the story on WP of the mitochondrial eve (sigh).

http://en.wikipedia.org/wiki/Mitochondrial_Eve David E. Volk

Thomas Mandel 17:55, 8 April 2008 (CDT)Sorry, I don't read Wikipedia. Reprint it here if you want.Thomas Mandel 17:55, 8 April 2008 (CDT)

Now I see the point your driving at and of course it's the same with the Y chromosome too. This sounds like a usage problem, i.e. each genome (ALL DNA, organelle and nuclear) is unique.

However, this is more complex than simply inheriting one mitochondrial genome from your mother. You inherit multiple mitochondria from your mother, read about heteroplasmy, so your population of mitochondria is not necessarily identical to your mothers. And the population within any given cell can change with time. The mitochondrial eve hypothesis is dealing with population genetics not individual genomes being passed between generations. Chris Day 10:40, 8 April 2008 (CDT)

OK, I broke down and looked at the article. Here is the problem with amateurs attempting to write technical articles, or conversely, the problem with technical types writing general articles. What is is about the mother that only she passes mtDNA on? As far as I could tell, after reading the entire article, nowhere is it mentioned "why" mtDNA is passed down from the mother only. The answer is not a difficult to find answer, it is quite obvious to a knowledgable reader, but if we assume that the reader is learning for the first time, without that answer a serious gap exists Thomas Mandel

Are you talking about the eve article? The heteroplasmy article is barely a definition but does lay out the idea that there is more than one mitochondrial genome in any one cell. Of relevance, I have seen genetics articles that postulate that sperm can rarely pass on a mitochondria organelle to the egg. Chris Day 23:14, 8 April 2008 (CDT)

mtDNA mutation versus 50% scramble at conception

mtDNA apparently does mutate faster, but the rates of mutation for both are still very low. Compare that to the 50% dad/50% mom shuffle at birth. The grandkids gets 25% of their nuclear DNA from grandma, but up to 100% of their mtDNA from her, unless a mutation has occurred. David E. Volk 10:37, 8 April 2008 (CDT)

It is always dangerous to talk about unique DNA since the terms usage depends on context. When comparing the genomes between two humans most of the sequence is not unique (most is identical), even between humans and chimpanzees most is not unique. Conversely, at the genomic level, one might consider identical twins to have no unique DNA (every base is identical), yet there will be differences between the two (somatic mutations). Does this mean that twins are actually unique? It is better to clarify the origins of the DNA; paternal (Y) or maternal (mitochondrial and X for males) or both (autosomes and X in females). Chris Day 10:47, 8 April 2008 (CDT)

I removed the "unique" hopefully the reader will not notice. Thomas Mandel 22:35, 8 April 2008 (CDT)

barcode/blueprint

The terms barcode and blueprint has been frowned on lately too, because thry omit things like alternate reading frames and epigenetics (ie. methylation patterns of the Cyt.s). David E. Volk 10:57, 8 April 2008 (CDT)

Obviously they are only analogies and they are fairly accurate for most cases. What is a better analogy? I think blueprint is much better than barcode. Barcode is going to give the same output regardless, very binary. Is that true of a blueprint? In theory yes, but in practice no, so this might work even within the framework epigenetic and alternate reading frames and splicing. Chris Day 11:31, 8 April 2008 (CDT)

Where do we use "blueprint?"Thomas Mandel 17:57, 8 April 2008 (CDT)

OK, I revised the usage of both barcode and blueprint, hopefully in a better way, Thomas Mandel 22:31, 8 April 2008 (CDT)

picture of mRNA entrance/exit sites on Ribosome

See this article for a discription of mRNA going into a ribosome.

http://biology.plosjournals.org/archive/1545-7885/5/8/pdf/10.1371_journal.pbio.0050209-L.pdf

David E. Volk 11:47, 8 April 2008 (CDT)

Great for another article but too much detail for this article IMO. Remember there is no direct role for DNA in ribosomes and translation. Chris Day 12:02, 8 April 2008 (CDT)

I looked at the pictures, the stereo made by crossing the eyes is great. But so what, I mused. Until I was reading in the old text I got, that the shape of the ribosome was not known at the time, and while some said it was groves, actually it is holes. What is interesting to me is that the ribosome constructs in a step by step process and that is interesting because it can now be said that the entire process of human developement is a complementary process. That is to say, the human body creates itself by working together and that can be summarized as a process of "this working together, assisted by an enzyme with that". That is, the fundamental principle of all living organisms is a "this and a that in a relationship forming something else". Much like clapping your hands together..Or a snap of the fingers. The problem is that this simplicity is covered by the apparent complexity. But it is clear and obvious in the DNA process, and even the ribosome has two parts, as does all membranes, and I would bet my life that ALL organizations in ALL living organisms can be described in this manner. Exceptions notwithstanding. Thomas Mandel 10:04, 10 April 2008 (CDT)

It all depends on how you define part. ;) Chris Day 11:06, 10 April 2008 (CDT)

I'm not the only one who thinks this, Jonas Salk too, You ask a good question. And I will have to spend some time to come up with a good answer. Right now I am thinking that the parts would be determned starting from the whole. If the whole whatever is divided how does it divide? Or to put it another way, do we divide DNA into two parts or do we divide it into a trillion parts? Actually nature gives us the answer to that, it divides naturally into two parts. (actualy this division is counted as three, because there is always the enzyme. That's part of it too.)Anyway , the question is too important to dismiss with a quick answer...whole parts? Let me sleep on this ne.Thomas Mandel 00:28, 11 April 2008 (CDT)

My book describes two "subunits" of the ribosome, the small subunit connects to the start codon and then the large subunit is attached to the small making one whole ribosome. So, maybe a "part" can be a "subunit" It is clear that DNA is made of two "subunits" so the question I am seeking the answer to is is everything in a living organism made of two subunits? Thomas Mandel 09:57, 11 April 2008 (CDT)

This may be impossible to prove, so what exceptions can be found. I have found two so far, one is the codon made of three base pairs, and the other is the strands of ligaments which exist as three strands. Is this a falsification or adaptation? Thomas Mandel 10:03, 11 April 2008 (CDT)

The biological usage of subunit usually refer to one protein in a complex, however, the usage is different for the ribosome. Each of the ribosomes large and small subunits have many more than two parts. For example, the small ribsosomal subunit in eukaryotes has a 1900 nucleotide piece of RNA and over 30 proteins. The large subunits is an even more complex complex. So what is a part? While I can think of several examples that might encourage the two part rule I can think of more exceptions. Chris Day 10:21, 11 April 2008 (CDT)

Ultimately, what a word means is not absolute, but can vary depending on many factors such as context and the theoritical base one is writing from. So "part" can mean something very different to me than it does to you. So when I am using part in the sense we are talking about, I am thinking more in terms as a conceptual part. For example I can think of DNA as two parts, the strands and the bases. Yet in most cases the sugar/phosphate and one base are taken together as in nucleotide. So if we take the nucleotide as the part we would be correct in saying that DNA is made of one part. Of course this is absurd, but still. At any rate, I can see the significance of defining what "part" means, maybe a different word would be better in my case. Aspect maybe...

possibly a model article?

I have noticed that the main headings seem to take on a kind of introductory approach. I wonder if we couldn't use this to an advantage. What I mean is that maybe the headings could purposely be written such that collectively they could tell a general introductory story. The advantage is that they could focus on a more general (not lower) approach, and then each elaboration in each section would introduce the more detailed (not higher) information. In other words the first paragraphs in each of the sections would collectively be a general (not lower) article. I think this is occuring naturally in this article. This would be a good article to attempt to do that. Also can the sub pages be used like a glossory? I had thought of doing this with a different article, that is, new words would be hyperlinked to a page with a simple definition. A idstinction would have to be made between such a page and a stub article thoughThomas Mandel 15:42, 9 April 2008 (CDT)

This was my goal. You'll note I mentioned it above. But I wanted to see how the text fell into place before starting to write intro sections that link concepts. Chris Day 16:10, 9 April 2008 (CDT)

I didn't catch your warning note, but I noticed the change after it occured. I like the idea a lot. Maybe I should repeat that - I like the idea a lot. There are a couple sections that I have no idea what they are about because they dive right into detail. Sometimes I think there are elfs working on this as I sleep...Are we headed toward taking the writing to a new level? Can the article on DNA evolve? Thomas Mandel

Growth vs construction

These are two different concepts; I'm not sure they're interchangable words. --Robert W King 22:26, 9 April 2008 (CDT)

I'm not sure either, but when I look at the details, stuff is put together as in construction. I was thinking that "growth" would be a better biological term. But now that you mention it, maybe "growth" does not actually happen. The body does not grow, it is constructed one tiny bit at a time X 10⁹ give or take What do you think?

Thomas Mandel 00:55, 10 April 2008 (CDT)

might be best to think of "growth" as proliferation of cells, "construction" as assembling themGareth Leng 03:09, 10 April 2008 (CDT)

I thought of population growth, fits in with proliferation. I wonder if it isnt one of those magic words that really do not explain anything. A crystal grows, a tumor grows, maybe all it means is "gets bigger"Thomas Mandel 00:38, 11 April 2008 (CDT)

Growth is just getting bigger. The growth of a plant leaf is a combination of cell expansion and cell proliferation. Growth is just a more general term, not a useless term. Some subcellular structures, such as microtubules, are dynamic and can grow within the cell. Chris Day 10:26, 11 April 2008 (CDT)

DNA methylation

I'm pulling this out because I don't understand what it does, and I can't find anything about it. Kornberg devotes two pages to it around page 600 or so. And he isn't sure what the role is either.

DNA methylation is ...

The expression of genes is influenced by the chromatin structure of a chromosome which may hinder or enhance accessibility of the gene. Regions of heterochromatin (with little or no gene expression) correlate with the methylation of cytosine. These structural changes to the DNA are one type of epigenetic change that can alter chromatin structure, and they are inheritable. Epigenetics refers to features of organisms that are stable over successive rounds of cell division but which do not involve changes in the underlying DNA sequence. Epigenetic changes are important in cellular differentiation, allowing cells to maintain different characteristics despite containing the same genomic material. Some epigenetic features can be inherited from one generation to the next.

The level of methylation varies between organisms; the nematode C. elegans lacks any cytosine methylation, while up to 1% of the DNA of vertebrates contains 5-methylcytosine. Despite the biological importance of 5-methylcytosine, it is susceptible to spontaneous deamination, and methylated cytosines are therefore mutation 'hotspots'. Other base modifications include adenine methylation in bacteria and the glycosylation of uracil to produce the "J-base" in kinetoplastids.

DNA methylation is an extremely important phenomenon, that underlies parental imprinting and other epigenetic influences. It should definitely be there but explained more fully. It wouldnt be in Kornberg, it's a story of the last decade really

I've trimmed some of the references - this was and I think still is a bit over-referenced. I've moved the textbook ref to the bibliography. Tom, I trimmed your last paragraph; I felt either you had to say a lot more or a lot less, and I don't think this is the place to say more, as it's a tangent. I've left your references in, and you could perhaps just direct to further articles in the last para (even where not yet written).Gareth Leng 04:12, 13 April 2008 (CDT)

I reinserted part of DNA Methylation. I hope to explain this simply soon.Thomas Mandel

Agree with Gareth, there is no way Kornberg would have had any idea of the importance of methylation. Until recently drosophila was assumed to have no cytosine methylation. Methylation was regarded as mainly a bacterial phenomenon in Kornberg's day. Chris Day 12:36, 13 April 2008 (CDT)

prior research...

I also inserted a definition of a system. I feel that the concept is also of extreme importance primarily because it represents a paradigm shift in the making and therefore it behooves us to portray it in a scientifically accurate way including the history which has been traced as far back as Aristotle in Western science and even further back if the Chinese are included. There are far too many claims that "systems theory" is a new invention when what actually has been invented is the computerized methodology. I believe that this is an ethical issue and if not corrected will lead to a science which cannot be trusted. It is trust, after all, that science lays claim to. Science, and those who report on science, must do everything it can to maintain this trust, and the manipulation of scientific fact for the benefit of a few is not justifiable by any means whatsoever. If science is to be trusted above all then science must demonstrate trustworhiness above all. And if this isn't enough, consider copyright law or patent law. Before a patent is granted, prior research must show that the invention is indeed an invention. Ignorance of the law is not a valid excuse. Ignorance of "prior research" is not grounds for "new discovery" claims Thomas Mandel 10:40, 13 April 2008 (CDT)

The discovery od DNA is a good example. For most of my life I assumed that Watson and Crick discovered DNA. Then I heard about the lady and her picture, and I wondered why she never was mentioned. IT wasn't until I started to research DNA for this article that I found out that the real discovery was in 1944, and that there was a long string of discoveries prior to Watson and Crick, and that what Watson and Crick did actually discover, on the morning of Feb. 28th, was something that any kid could do, given what they were given. There are far too many examples of the manipulation of scientific fact to serve the purposes of a few. When the body is confronted with a dis-ease, antibodies are created and the source of the dis-ease is wiped out. It can be that simple...Thomas Mandel 10:59, 13 April 2008 (CDT)

There is no way any kid could figure out the way that the bases paired. You would have needed a good handle on the possible hydrogen bonds for starters. Parallel or antiparallel? It is an elegant structure but that does not make it simple. I'm not sure I understand your antibody point? Chris Day 12:30, 13 April 2008 (CDT)

They didn't discover DNA and never claimed to. They guessed that the structure held the key, they solved the structure, and they saw the implications of the structure; it was a sheer intellectual tour-de-force; no experiments, just the power of thought and imagination. Big discoveries often seem obvious after the event. But at the time, no, this was a problem that many of the very best scientists were all chasing, and the answer pretty well came like a bombshell. Clear, elegant, and yes, obvious in a way; but only afterwards. Gareth Leng 12:52, 13 April 2008 (CDT)

Well, I listened to the interview of Watson (?) telling about how he couldn't wait to get the models back so he cut them out of cardboard and when moving them around saw how they formed identical shapes. I don't mean to demean Watson, but... The real point I want to make is that I was led by my ignorance to assume that they discovered DNA.

The antibody point refers to Gareth's comments and that is about a long story we were involved in. When the Genome Project reached maturity, apparently it became obvious that much more was needed to understand life than just an understanding of the parts. This realization led to the creation of what they call systems biology. Now, if one goes to systemsbiology.org, the impression is given that they have formed that new kind of scientific inquiry. Nowhere in that site is there any indication that "integrative systems" is actually an old science which was developed by many and in particular by the biologist Ludwig von Bertalanffy who authored in 1968 a book called General System Theory.

One of the references refers to this concept as General systemology because the "theory" in the title is actually a mistranslation of the original German "Theorie" which is more like teaching. And in fact since that time hundreds of societies and even federaton of societies have emerged related to "systemology" They have, since the very beginning used the term "systems theory" to describe their science. Tens of thousands of papers have been published about systems theory. But because mainstream science evolved as a reductionistic science, systems science was largely ignored by the mainstream.

Enter the computer. With the computer scientists were able to model systems mathematically and they soon found out that many systems are non-linear. From this emerged the "new science of complexity"

Well, a system by definition is a complex system. And complexity was in fact discussed fifty years ago. So what is "new" about complexity? The computer methodology. And rather than acknowledge "prior research" those who reported on this new science fell for it and furthered the notion that complexity was in fact "new"

Enter the Genome Project and systems biology. The story is the same. Systems biology is a new science. Well, there would be no problem in my estimation if systems biology stuck to what they have developed and called that new. But they, like complexity science, attempt to incorporate all the old notions as well and then imply that it was they who have reached ALL those conclusions. It's like the fellow who invented the automatic transmission trying to patent the entire automobile.

It is my understanding that every scientific paper must determine and acknowledge what is called "prior research." Ironically some have actually told me "I'm too busy to research that."

Well, it has to do with credibility and integrity. A job given to the antibodies...Thomas Mandel 13:42, 13 April 2008 (CDT)

Who do you think designed the models that Watson was waiting for?

I don't know, didn't they know the structure of the molecules beforehand?

So why did nobody else figure it out? Also, I challenge you to give the same models to even an undergraduate biologist and see if they figure out how they stack and pair without. Chris Day 15:32, 13 April 2008 (CDT)

I wasn't trying to diminish their achievement. I once designed something that an expert in the field came up to me and said he thought a genius designed it when actually it was an accident on my part. The difficulty is being in the right place at the right time doing the right thing and knowing the significance of what accidently happens. I was speaking more about my own ignorance in assuming that they did it all. Thomas Mandel 17:40, 13 April 2008 (CDT)

I'd say much of the above is your interpretation of what happens in biology rather than the reality. I doubt systems biologists consider the study of systems as new. The application to biology is new from a genomic perspective (and how can it not be the data to make it a reaility has only just arrived). It is not even new to modern biology, control theory in metabolism has been standard for years even if slow to catch on (read about Kascer). That the novelty of a "systems approach" to biology is exaggerated is PR, it looks better in grants, it looks better in the media. You have to realise that scientists are competing for money that is given to them by politicians. That means the message is often directed at them. How often do you read of the next "miracle cure" for cancer in the press? You write above as if scientists ignore what has gone before. I suggest that is rarely the case. Chris Day 13:54, 13 April 2008 (CDT)

I didn't mean to get into an argument and destroy all that we have accomplished together. Nor is this the time or place to have this discussion. Nevertheless, I have a paper here from the Dec 2007 journal Quarterly Review of Biology and an article coming from the Department of Theoretical Biology and Departement of Neurobiology and Cognitive Research at the University of Vienna, and the first paragraph of this paper reads --

IN TERMS OF publications, “systems biology” is currently an exploding field (see,

e.g., Chong and Ray 2002; Grant 2003). Note, however, that system thinking is not at all new in biology. In the sciences of life, it can be traced back at least to the German “teleo-mechanicist” tradition inaugurated by Immanuel Kant’s Critics of Judgement, of which Johannes Mu¨ ller and Karl von Baer were the main proponents (Kant 1789; Lenoir 1982). More generally, integrative (or “holistic”) thinking is not a “discovery” of the 20th century. It has a rather long history going back to ancient Greek thinkers: Aristotle already claimed that “the whole is of necessity prior to the part” (Aristotle 1966:1253a20). Between the 14th and 16th centuries, it was a major intellectual trend, which strongly reemerged at the turn of the 19th century in German Romanticism and post-Kantian idealism. Among others, Nicholas of Cusa, Gottfried Wilhelm Leibniz, and Johann Wolfgang von Goethe are considered “precursors” of modern systems thinking (Bapp 1921; Bertalanffy 1926a; Harrington 1996). One of the leading figures, who recurrently referred to those thinkers, is the philosopher and theoretical biologist Ludwig von Bertalanffy (1901–1972), mostly known for his project on a “general system theory” (GST). Unsurprisingly, he is still regularly quoted—although mostly laconically—by advocates of “systems biology” in the early 21st

century (e.g., Chong and Ray 2002).

So there is more than just my interpretation. I do agree that grant money fuels most of the PR work, but is that what science has evolved to? And who are we here to listen to. the science or the PR people? And what about when they misunderstand for example taking the notion that the whole picture has to be taken into account when really the crux of systems theory is a different ontological perspective e.g., from an emphasis on entities to an emphasis on the organization of entities? I ask this because when I do find a mention of systems theory it usually talks about the whole and usually fails to mention the relationships that make the whole in the first place, When we experience a whole, what we are experiencing is the relationships. Thomas Mandel 15:22, 13 April 2008 (CDT)

I'm not really arguing just giving you the perspective of a biologost. I don't understand the context of the quote or you have misunderstood what I meant by "it is your interpretation". What I meant by that is it is your interpretation that biologists are ignoring the history. Do you think any biologists would object to the paragraph you just quoted? Chris Day 15:32, 13 April 2008 (CDT)

I just looked at the systems biology website again. I think it is wonderful that this knowledge is finally getting out. I hope that in the future the work of early researchers will be acknowledged and I am sure that eventually it will be. I just received email about a paper talking about systems and chemistry, haven't looked at it yet. They mention in the systems biology web site that "Perhaps surprisingly, a concise definition of systems biology that most of can agree upon has yet to emerge," R. Achersold Ph.D Institute for systems biology. Well, Klir once wrote that he has over one hundred definition of systems in his notebook.

Because systems is a meta theory, any specific definition will depend on who the definer is. In our work at the Primer group, we had to devise a two part complementary definition in which Part A was the general definition and Part B was the specifics. Our part A was "A system is a family of meaningful relationships among the members acting as a whole..." and part B was that plus specific aspects which numbered around thirty complementaries before Marcus said "That's enough for now."

Just to close this story, my own interest came from an event in 1972 from which I figured out that the Universe worked as a system. However, it took 22 years of research before I found systems theory. It is not made obvious in the literature. My poetic version went like this "This and That in a loving relationship is something else." I think however that the essense of integrative systems can be captured in two words ---

working together

I can't wait till the politicians discover systems theory. Thomas Mandel 17:32, 13 April 2008 (CDT)