User talk:168.../DNA

Dear 168...: I gather that we have both been frustrated by Lir's no-doubt well-intentioned attempts to improve various articles related to biological topics. I was trying just now to fix the DNA article, but you reverted ("ibid.") in a way that also undid the changes I had incorporated. I agree that the changes that I'd made did not address all the problems of Lir's creation, but my plan had been to fix things incrementally (section by section). In short, I'd like to work with you on improving the article, but at present I'm not sure whether your reversion was specifically intended to "undo Lir's damage as quickly as possible" or whether you also had some reservations about the specific changes I'd made. Peak 09:12, 4 Jan 2004 (UTC)

I was intending to do the former. Sorry for squelching your additions and not having the patience to work with them. I agree it would be good to mention where DNA is found. 168... 16:47, 4 Jan 2004 (UTC)

Thanks. More recently, you made some other minor mini-reversions, two of which you definitely should reconsider:

1) This transmission of DNA is the primary mechanism of biological inheritance in all organisms.

I added the last phrase as the sentence is otherwise false (because of RNA-based viruses). I realize you might be leaning heavily on primarily, but I think the link to organisms is useful here anyway.

2) Each vine-like molecule is a strand of DNA: A chemically linked chain of nucleotides, which each consist of ...

Firstly, the capitalization of the 'A' after the colon is normally regarded as incorrect; secondly, '[PLURAL NOUN], which each [SINGULAR VERB]' is grammatically wrong. The intended meaning is 'each of which consists of', but that is awkward because of the two occurrences of 'of'. Perhaps ', each consisting of' works for you?

I think the post-colon capitalization is a style issue about which authorities disagree. I will have to look up the ", which each" issue. If you're right, I will have to thank you, because that's definitely a blind spot of mine. Sounds all right to me, but when I search Google News I see my usage is rare or non-existent.

[Peak:] Post-colon capitalization has its place, but not here. Anyway, it seems someone else already attended to both issues. Peak 05:15, 6 Jan 2004 (UTC)

I would also like to propose that the first few paragraphs be simplified based on a clearer distinction between the 'DNA double helix' and the concept of a 'strand of DNA'. Would you like to take a crack at that first? Peak 07:30, 5 Jan 2004 (UTC)

I agree the strand/molecule/double-helix distinction should be clear. I just bolded "double helix," and in the version up right now (my last edit), I think the distinction is explained well.168... 02:26, 6 Jan 2004 (UTC)

[Peak:] There is some disagreement about whether the 'double helix' is one molecule of DNA or two, r.g. here's a quotation about bacterial DNA:

The nucleoid is one long, single molecule of double stranded, helical, supercoiled DNA... [1]

That reference is talking about a bacterial chromosome, which is circular. Because it's circular and because the strands can twist either an even or an odd number of times around each other in circling, a bacterial chromosome sometimes really is one molecule, and sometimes it isn't. That's probably so disturbing to contemplate that biologists have been driven to fudge it and call it always a molecule. You might note thought that the DNA article talks about "pieces of DNA as people usually think of them" (or something like that). That's referring to a linear fragment, which unambiguously is two molecules, at least as I like to use the word "molecule."168... 06:45, 7 Jan 2004 (UTC)

Even if there is a clear answer either way, I am inclined to think that the matter is a bit esoteric. As we've agreed, the focus should be explaining what a DNA strand is, how it forms a double helix, etc etc. Peak 05:15, 6 Jan 2004 (UTC)

If it's esoteric, it's only because people are sloppy. To the people whose business is molecules, namely chemists, a linear fragment of double-helical DNA is very definitely two molecules, because the strands are connected only by H bonds, which are not "chemical" or "intramolecular" bonds. Why perpetuate vagueness and sloppiness?168... 06:13, 6 Jan 2004 (UTC)

[Peak:] Please understand that I understand and respect what you're saying. However, after having done quite a lot of checking, it is clear that your position is by no means universally held, and appears not to be shared by many biologists. Various authorities are quite explicit that, in the words of Michael W. Davidson:

There is a single DNA molecule per chromosome. [2]

That text appears to have been written by a microscope technologist--not the kind of person I would ask to arbitrate this nomenclatural issue.168... 06:57, 7 Jan 2004 (UTC)

Alas, my search revealed many such quotations, but, apart from your (always splendid) work, I have yet to find a single reference to the double helix as consisting of two molecules. But I'll keep looking :-) Peak 08:31, 7 Jan 2004 (UTC)

Allow me to help:

168...

[Peak:] Actually, these specific quotations do not help your case at all. We have always agreed that "Two DNA molecules wind up into a double helix". The question is: what then? Anyway, I agree with your idea that we should explain what we mean, though I would prefer to avoid "strictly speaking" and say exactly what is meant. (Something like: "The DNA double helix is composed of two strands of DNA. Since there are no covalent bonds holding them together, organic chemists would say that the double helix is composed of two molecules of DNA. However, the various forms of DNA do have different physical and chemical properties and so, using an alternative definition of the concept, it may also be said that the double helix forms a single molecule.") Peak 08:50, 9 Jan 2004 (UTC)

I'm surprised you say those quotes don't address your concerns. I guess I didn't understand what they were. Anyway, I don't think the elaboration you describe is necessary in this context. "Molecule" here is like the word "fire" in the sentence: "Let me remind you that the the South Winslow Hellfire of 1954 was not a single fire, but a conflagration of several fires, one of which was arson, but three others of which were started by natural causes." I see nothing wrong with the use of "fire" in that sentence. Meanwhile, I don't think the second definition of molecule really deserves addressing. It's very rare that anything people call a molecule in this second sense isn't also a molecule in the first sense. I doubt a dictionary for chemists would even admit to the existence of this usage of "molecule", except as a common slip that occurs when chemists discuss macromolecular assemblies and poets wax microscopic. 168... 16:45, 9 Jan 2004 (UTC)

Streitwieser seems to address your "what then?" concern. Quoting him again he says: "DNA is actually a double-stranded helix of two individual molecules about 20 (Angstroms) apart." But I guess the degree to which that addresses your concern may depend, as they say, on what your definition of "is" is...and possibly also your definition of "of." 168... 18:53, 9 Jan 2004 (UTC)

[Peak:] The Streitwieser quotation is exactly what I was hoping one of us would find. Thanks! (Sorry, but I have no "is" or "of" quibbles. As I said all along, I'm comfortable with the fact that in natural languages, many words have multiple meanings. I was, however, quite impressed that the Longman Web Dictionary gives thirty-five definitions for "life".)

Nevertheless, having had some time to ponder all this, I do find the covalent bond definition a bit of a stretch when applied to such huge "molecular complexes" as the double helix. After all, the helix is NOT formed as the result of the intertwining of previously existing molecules. It's all a matter of "Margins of Precision" (the title of a book by Max Black). Peak 08:53, 10 Jan 2004 (UTC)

I don't consider it correct to generalize that the helix isn't formed "as the result of the intertwining of previously existing molecules." Not formed INITIALLY in the narrow context of biological replication, but disentwined and RE-FORMED endlessly as cells transcribe and express their genes or as PCR machines de-anneal and anneal the synthetic DNA in a test-tube. 168... 17:56, 10 Jan 2004 (UTC)

Similarly, there are many references to "the double helical structure of the DNA molecule". In particular, JDW seems to write consistently in this manner.

The reason may simply be that there are effectively two definitions of "molecule" in circulation: the detailed one that emphasizes covalent bonds, and the general one that goes like this:

The smallest particle of a substance that retains the chemical and physical properties of the substance.

But what is the essential substance regarding DNA? True, our chromosomes are double helical while their sitting around and preserving our genetic inheritance. But the "sense" strands that encode our proteins and undergo transcription are single strands. Also, our genetic material can be copied and passed on only if the double-helical strands are first separated. Finally, chromosomes exist which are single strands of DNA, such as the chromosomes of certain viruses. 168... 06:57, 7 Jan 2004 (UTC)

Who said anything about "essential substance"? The quoted definition just refers to humdrum properties.Peak 07:57, 7 Jan 2004 (UTC)

But the humdrum properties of what? DNA is sometimes double helical and sometimes single stranded. Which DNA are we talking about? Which is the essential DNA?168... 08:21, 7 Jan 2004 (UTC)

[Peak:] The issue under discussion is whether the DNA double helix consists of one or two molecules. There is no need to worry about essences or even quintessences, at least not yet :-) Peak 08:36, 7 Jan 2004 (UTC)

The quintessence is important, because the definition of molecule you are quoting pertains to "the substance." What substance are we talking about? The double-helical substance, which has one set of length and sequence-dependent properties, or a strand of DNA, which has a different set of length and sequence-dependent properties? Which substance "owns" the word "DNA"? I think both do, although I'm sure you could find people to argue either way.168... 18:26, 12 Jan 2004 (UTC)

Yes, I must concede that when the question is "Is the double helical substance a molecule", then by the definition you aptly recruited above, the answer is yes, and so the assertion in the article that "pieces of DNA as people typically think of them are not single molecules" is false. But there exist other definitions of "molecule", and some such as me would call them stricter definitions. According to those, the statement is true. If we accept the existence of both usages of "molecule" we might be tempted to say the assertion is confusing, although in context I don't think it is. I wouldn't mind modifying it to say "are not in the strictest sense single molecules." One reason for making the point is that the article describes strands just two sentences later, according to custom, as polymers. If we call the double helix one molecule, then by saying it is composed of two polymers we are contradicting ourselves...although this is what people normally do when writing about this subject.168... 08:52, 7 Jan 2004 (UTC)

and another reason to make the two-molecules point is that it helps people make sense of why the double helix splits in two upon gentle heating, as the article says farther down. This property is the basis of PCR, and their easy separability more generally is essential to replication and transcription. It's more than a distraction. 168... 20:44, 7 Jan 2004 (UTC)

Perhaps biologists tend to take the viewpoint that the double helix is a macromolecule, and that every macromolecule is (hopefully) a molecule.

Physical organic chemists distinguish between a "molecules" and "molecular entities", the latter term covering both "molecules" and other complexes. This is a perfectly valid distinction for physical organic chemists to make, and perhaps it's the one you are making, but do physical organic chemists in fact insist that the DNA double helix consists of two molecules?

Here's your answer, from the standard text Introduction to Organic Chemistry by world-reknowned physical organic chemist Andrew Streitweiser and coauthor Clayton Heathcock (Third Edition, p.1120). "DNA is actually a double-stranded helix of two individual molecules about 20 (Angstroms) apart." Of course, he refers to a double helix as a "molecule" a few sentences before that one, but never mind. He got it right in the end. 168... 16:46, 7 Jan 2004 (UTC)

:-) Peak 08:50, 9 Jan 2004 (UTC)

In summary, it seems that whereas the criteria you are using exclude the significance of the intertwining of the DNA strands in a double helix, others would say that such intertwining does have significance for the physical and chemical properties of the double helix.

In any case, regarding the introductory parts of the DNA article, one simple solution would be to describe the DNA double helix as a "macromolecule" composed of two DNA strands. Peak 05:58, 7 Jan 2004 (UTC)

I'm impressed by your diligence and research, but I'm sticking to my guns. Watson's a crank and a nut and on top of all that a biologist, not a physical scientist. Although I realize that human language isn't consistent or logical, I try to be anyway, and I don't see how one could get two molecules--as I think everyone would regard two non-interwined DNA strands--from "one molecule"--as some people seem prepared to call a piece of double-helical DNA--without breaking a single chemical bond in that "molecule." I am familiar with the shakey terrain of "macromolecule" and in particular that which goes with "protein." I have created new articles and made the rounds of existing ones spelling out the ambiguity in that word, which no biochemistry book or paper ever spelled out for me, and which I think few are conscious of. But "protein" is used equally often to refer to single molecules, such as protein subunits and to refer to multi-subunit holoenzymes and assemblies such as hemoglobin. On the other hand, although microtubles and actin are composed of subunit proteins, I think scientists never refer to one of them as "a protein", and instead call it more often "a macromolecular assembly" or something along those lines. Meanwhile an ion channel is called a protein in some contexts and a "multimer" in others. I think these usages illustrate that neither "protein" nor "macromolecule" is used consistently. Perhaps this supports your point. Nevertheless, my sense is that this looseness is confined to biology. Since not only biologists read Wikipedia, I think it's best to use a conservative definition of molecule. But anyway, I don't think that in anyone's book it would be regarded as inaccurate to call a strand of DNA a molecule, and I think that doing so as the article does now both alerts people to the possibility of confusion and helps them along in understanding what the double helix is. 168... 06:37, 7 Jan 2004 (UTC)

That was kind of rambling. Let me just say this: The word you suggest, "macromolecule" is vague and esoteric. It's probably a worthwhile word to expose people to in this context, but unlike "molecule," I think we can't expect it to do explanatory work for us. 168... 07:18, 7 Jan 2004 (UTC)

Until we can come up with some third party's endorsement of the view that the double helix is composed of two molecules, I believe the introduction should avoid the distraction. Peak 07:57, 7 Jan 2004 (UTC)

I think that's an unfair burden of proof. How about a third party endorsement in favor of calling a DNA strand a molecule and a failure after due diligence to find a strand called "half a DNA molecule"? 168... 08:21, 7 Jan 2004 (UTC)

"The final stage in the formation of a strand of DNA is to covalently link one deoxyribonucleotide triphosphate to another to give a polymeric molecule (a polydeoxyribonucleotide ie DNA)".
"The replicative form replicates and gives rise to single stranded (the + strand) molecules which are packaged into phage and extruded from the cell."
From[[3] "The phosphodiester linkage of monomer units into a polymeric molecule is called the primary structure. (Figure 4.1)." Emphasis added, but note that the polymeric molecule of DNA in Figure 4.1 is a single strand. 168... 08:21, 7 Jan 2004 (UTC)

[Peak:] Looking a little further:

 Features of the Model for B-form DNA
   * Two strands.
   * Strands are wrapped plectonemically in a right handed helix (Figure 4.10c).
   * Phosphates are on the outside of the molecule.
   * Base pairs are in the inside of the molecule stacked close to each other.

Yes, that's 'molecule'! You'll have to try again :-) Peak 08:28, 7 Jan 2004 (UTC)

It's clearly standard to call a double helix a molecule. I am just trying to show that it's accurate to call it two molecules according to a standard definition of "molecule". I take it your "Looking a little further" excerpt comes from my source 3. What that shows is that the same person uses "molecule" inconsistently. S/he calls a strand the "primary structure" of DNA and a "molecule", but as you saw s/he also calls a double helix a molecule, as is the tradition.168... 08:38, 7 Jan 2004 (UTC)

Just to interject, this is something I think I am qualified to comment upon. A DNA strand is a single molecule. A DNA double-helix is a single complex. Although this double helix is commonly refered to as a molecule, this is a mistake; it is definitely two molecules. It is very easy to cite some eminent scientist or other who refers to the double-helix as a molecule but it is still, strictly speaking, wrong! Stewart Adcock 17:53, 7 Jan 2004 (UTC)

Another interjection here from a scientist in the field of DNA structure. To be precise, a strand is a molecule. But scientists (myself included) are sloppy with language and often refer to the double helix as a molecule. But when it really matters whether it is a single molecule or not (crystallography, mass spectrometry, annealing, single molecule experiments, chemical modification, etc.), it is the strand that is recognized as a molecule. In addition, in cases of uncertainty, I suggest consulting review papers or reference texts , such as texts on nucleic acid structure and chemistry, rather than web pages or introductory biology textbooks. Cheers. Holeung 10:09, Jan 12, 2004 (UTC)

I hope you aren't dissing Streiwieser when you refer to "introductory biology text books"! (his is an organic chemistry textbook with chapters on hybrid electronic orbitals and antibonding). I think you have a point that nucleic acid research papers are one of the best places to look for usage and the authors of these papers represent one of the groups of people who are "DNA experts" and might be invited to have the last word. But DNA extends beyond one group's research interests. I think we have to make a subjective judgment call when we decide which experts to pick to give us the right language for a general readership such as WikiP is trying to reach. My preference was to ask a physical organic chemist, and I could offer reasons for it, if you are interested. I encourage you to be more open minded about the Web as a research tool. For example, if you were to read Nucleic Acids Research online, you could save yourself a trip to the library.168... 17:21, 12 Jan 2004 (UTC)

Are genes "encoded"?

(spun off from Talk: DNA)

One problem with that version is that genes are not encoded by anything. Genes encode other things. Other things don't encode genes. 168... 06:33, 6 Jan 2004 (UTC)

We will have to disagree on that point. Since there isn't a universally agreed definition for gene, there's not much we can do about that. I say that genes are encoded, by the nucleotide alphabet, in the chromosomes. Stewart Adcock 07:42, 6 Jan 2004 (UTC)

I'd be willing to agree to disagree, but I suspect we don't really disagree: I predict you will agree that it's fair to say a gene is "made up" of nucleotides, and in very much the same straightforward way that the sentence you are reading now is "made up" of letters. Well, that sentence is obviously in english, and not in code. So I would be surprised if you would want to say it's been encoded by some person or some thing like an algorithm or a computer or a key. I think the first molecular biologists hit on a very good and strict analogy when they used the metaphor of "code" in naming the genetic code. Lots of journalists probably never understood or really noticed the analogy, and so perhaps a sloppy use of "encode" in the media has backwashed into science (exacerbated by the fact that "encode" sounds cool, and so even scientists wants to use it as much as possible). But I think that being sloppy with it is to squander a beautiful and instructive metaphor, and so we should all clean up our act. 168... 23:20, 6 Jan 2004 (UTC)

But that's the whole point. I don't think that it is really fair to say a gene is "made up" of nucleotides (if by "made up" you mean consists of). I do want to say that genes are encoded, by the nucleotides, in the chromosomes (which are "made up" of nucleotides). Irrespective, this discussion is rapidly extending beyond the scope that it useful for this article! Therefore, if you wish to continue this thread, I'd suggest we move it to one of our talk pages! I think I do understand exactly what your point is but I just don't agree, sorry. Stewart Adcock 00:28, 7 Jan 2004 (UTC)

Can't you imagine a conversation such as this in a molecular biology lab:

Hey, Joe, what did you say you were splicing into that plasmid?

A mutant GFP gene

And what's it made of?

It's just the standard GFP sequence with a substitution at position 13, which improves expression

No, I mean what did you make it from?

Oh, you're asking if it's hot?

Yes.

Yeah. I polymerized the fragments with ³⁵S-ATP

O.K., so when the gene inserts into chromosome 3 it'll be hot."

Right.

These people are talking about a gene that is made up of nucleotides, some of which are radioactive. I think they are making a standard usage of the word "gene." Could you spell out the sense or meaning of "gene" in which it is reasonable to say that a gene is "encoded" by nucleotides?168... 18:26, 7 Jan 2004 (UTC)

I would have to imagine that because I try to avoid entering molecular biology labs at all costs. ;-) Anyway, yes I agree that one might hear such a discussion. But to be strictly correct, I believe, they should say "a mutant GFP cistron", and maybe, "so when the sequence inserts into chromosome 3 it'll be hot". My preferred definition for gene goes along the lines of, "A gene is any portion of a chromosome that exists as a unit for natural selection". So rather than having nucleotides making-up genes and genes making-up chromosomes, nucleotides make chromosomes and some (not-neccesarily contiguous) chunks of the chromosomes have the property of being genes. By my definition (actually, IIRC, it's G. Williams definition according to Richard Dawkins) it is more natural to say that the genes are encoded by the particular nucleotides in the chromosome, since as soon as it is out of its original chromosomal context (i.e. it is a string of nucleotides synthesised in a lab) then its no longer a gene! (indeed, I am told that after moving those exact nucleotides to a different location in that chromosome or another chromosome then they might no longer act as a gene (or cistron).) I've also just realised something: Note that my use of encode is somewhat different from that in "this gene encodes a protein", which might be causing some confusion. Stewart Adcock 07:55, 9 Jan 2004 (UTC) (while he awaits T6 with baited breath! ;-) )

"Gene" is famous for being hard to define, but really it should be more famous for having multiple uses and meaning different things in different contexts. It's hard to say what might be the primary sense of "gene," but one I've heard again and again in mo-bio labs applies to pieces of DNA. If by "gene" we were refering to a sequence in the abstract, I believe we wouldn't talk about cloning it. People don't seem ever to say they "typed a gene" into a computer. They seem to prefer to say they typed in "the sequence of a gene." I think that when one inserts a gene into a chromosome material is being inserted. The chromosome becomes bigger and weighs more in proportion to the amount of sequence that was inserted. 168... 17:12, 9 Jan 2004 (UTC)

I can probably agree with that! Stewart Adcock 18:38, 9 Jan 2004 (UTC)

Well, then probably you have agreed that it is accurate to say nucleotides 'make up' genes, in the same sense that Latinos make up a percentage of the U.S. population. You didn't seem to agree that this was fair to say before. 168... 19:15, 9 Jan 2004 (UTC)

No! I was disagreeing to your assertion that it is unfair to say "genes are encoded". (At least that's what I recall... the discussion over at DNA has been going on so long, and changes tack so often, that I'm beginning to lose a full appreciation of what's going on). Stewart Adcock 17:14, 11 Jan 2004 (UTC)

Yes, I think that was the original and main thing you disagreed with, but in trying to bring you round to my perspective, I began by building a case on the assumption that you would agree on the use of "make up." You replied that you did not accept that usage, so we ground to a halt. Since that was the only stumbling block to agreement you mentioned, I was excited when we seemed to have resolved it, but I realize now that there might be unstated others in the way. Anyway, I suppose it's not worth the trouble.168... 08:26, 12 Jan 2004 (UTC)

No, I don't suppose it's worth the trouble. Nonetheless, I did (hesitantly) agree to the use of "make up" in the article fairly quickly... although if I was writing it myself (i.e. without reference to anybody else's opinions) then I'd still choose "encode"! Stewart Adcock 20:18, 12 Jan 2004 (UTC)