Saturday, November 10, 2012

The Central Dogma Dies Again! (not)

You expect IDiots to be idiots so it's not surprising that they consistently screw up their analyses of scientific papers. The latest is a post by David Taylor on the Central Dogma of Molecular Biology [Revisiting the Cental Dogma] [Revisiting the Central Dogma]. He has just noticed a paper published in 2011 where two scientists challenge the Central Dogma. Naturally, this is interpreted to mean that Intelligent Design Creationism is true.

It's frustrating to read yet another scientific paper announcing the demise of the Central Dogma of Molecular Biology. If you've been following the literature, you'll know that the Central Dogma is regularly killed off about ten times per year—a rate that's been fairly constant for thirty years. But to paraphrase Mark Twain, reports of the death of the Central Dogma are greatly exaggerated.

Let's look at the paper by Sarah Franklin and Thomas M. Vondriska from the David Geffen School of Medicine in Los Angeles California (USA) (Franklin and Vondriska 2011). This is a paper that specifically addresses the Central Dogma of Molecular Biology so you'd expect that the authors understand what they are attacking, right?

Here's the opening paragraphs ...
Arguably the greatest postmodern coup for reductionism in biology was the articulation of the central dogma.1 Not since “humors” were discarded from medical practice and logic and experiment instituted as the cornerstones of physiology (which they remain today) had such a revolutionary idea transformed biology and enabled scientific inquiry. Because of its simplicity, the central dogma has the tantalizing allure of deduction: If one accepts the premises (that DNA encodes mRNA, and mRNA, protein), it seems one cannot deny the conclusions (that genes are the blueprint for life). As a result, the central dogma has guided research into causes of disease and phenotype, as well as constituted the basis for the tools used in the laboratory to interrogate these causes for the past half century.

The past decade, however, has witnessed a rapid accumulation of evidence that challenges the linear logic of the central dogma. Four previously unassailable beliefs about the genome—that it is static throughout the life of the organism; that it is invariant between cell type and individual2–4; that changes occurring in somatic cells cannot be inherited (also known as Lamarckian evolution5); and that necessary and sufficient information for cellular function is contained in the gene sequence—have all been called into question in the last few years. Revelations of similar scale have occurred in the transcriptome, with the discovery of the ubiquity (and variety) of mRNA splicing.6 So too with the proteome, which has undergone perhaps the most dramatic shift in understanding as a result of the aforementioned changes to the transcriptome and the genome, as well as by the explosion of technology development that has enabled both quantitative and qualitative analysis of large groups of proteins and their modifications in a single experiment. It is now clear that information flows multidirectionally between different tiers of biological information, of which genes, transcripts, and proteins constitute only the most obvious 3.
Reference 1—the reference to the meaning of the Central Dogma—is the Nature paper published by Francis Crick in 1970. That paper was intended to clarify the meaning of the Central Dogma after the discovery of reverses transcriptase. Crick was concerned about the fact that many scientists were confused about the meaning of the Central Dogma so he attempted to set them straight by clearly stating that the Central Dogma was NOT "DNA makes RNA makes protein" (the Sequence Hypothesis) but ....
... once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958)

The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid. (F.H.C. Crick, 1970)
I explained this in Basic Concepts: The Central Dogma of Molecular Biology.

Since Sarah Franklin and Thomas M. Vondriska reference the 1970 Crick paper, you'd expect them to have read it but they clearly haven't read it at all or they would know that their definition of the Central Dogma is wrong. I don't understand how this happens. How is it possible that two scientists could publish a paper criticizing the Central Dogma without even knowing what the Central Dogma actually says? How is it possible that the reviewers and editors of this journal could let such a paper be published?

For that matter, how is it possible to publish yet another paper announcing the death of the false version of the Central Dogma? How many times can you beat a dead horse even if it's a mythical horse?

Footnote: Let's look at the "Four previously unassailable beliefs about the genome."
  1. (the genome) is static throughout the life of the organism. We've known that this is untrue since the 1970s when genome rearrangements in bacteria were discovered. We've known about immunoglobulin gene rearrangements for over twenty-five years. We've known about mating type in yeast for at least as long as that. We've known about drastic genome rearrangements in protozoa since the 1980s. I assume that what Franklin and Vondriska really mean to say is they have just discovered what they should have learned as undergraduates.
  2. (the genome) is invariant between cell type and individual. See above. Read a textbook.
  3. changes occurring in somatic cells cannot be inherited (also known as Lamarckian evolution. I'm not sure what this means. Do they mean that changes occurring in somatic cells can somehow be transferred to the germ line and inherited by offspring?
  4. necessary and sufficient information for cellular function is contained in the gene sequence. A basic principle of biology is that you need a cell to make another cell. Most people learn this in high school.

Crick, F.H.C. (1958) On protein synthesis. Symp. Soc. Exp. Biol. XII:138-163.

Crick, F. (1970) Central Dogma of Molecular Biology. Nature 227, 561-563. [PDF file]

Franklin S. and Vondriska, T.M. (2011) Genomes, Proteomes, and the Central Dogma. Circulation: Cardiovascular Genetics 4:576 [doi: 10.1161/​CIRCGENETICS.110.957795]

20 comments :

  1. I suspect this is driven not (entirely) by misunderstanding but by the modern need for every paper to revolutionize the field. Press release hype, in other words, has invaded the actual publications. In order to revolutionize the field you have to show that some predecessor, the more prominent the better, was wrong. Crick is only number two in prestige, after Darwin, and I'm sure you could show this by counting the number of times per year that each is proven wrong. Junk DNA (author unspecified) is another prominent target.

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  2. To me the Central Dogma is simply this:

    DNA <-> RNA -> Proteins

    It is perfectly possible to be a neo-Lamarkian and subscribe to the central dogma for example Ted Steele.

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    1. I better add of course that my arrows refer to information flow not conversion. Just in case some IDiot misses that.

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    2. If you insist on using a diagram, then you should use the triangle version that Crick used in order to show that information cannot flow from protein directly to DNA. The version you use is easily confused with the sequence hypothesis.

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    3. Sorry but it is just easier to produce a linear diagram with a keyboard. Any way it just lists the permitted routes of information transfer.

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    4. Maybe you could use parentheses?

      ( DNA <-> RNA ) -> Proteins

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  3. NNNNNNNNN -> aa-aa-aa

    aa-aa-aa /-> NNNNNNNNN

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  4. I remember a paper the SGU talked about where this kind of crap hype did actually get researchers more support.
    ...or the paper was more about the researchers themselves causing the majority of ridiculous claims well before the science reporters came along, the hosts just speculated about this, and I'm not being rigorous enough to hunt it down so I give people accurate information.

    My initial searches haven't turned up anything but if anyone recognizes the paper I'd definitely appreciate a refresher so I can tell if I just tried to make things up.

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    1. I think you are referring to a study that showed that lines directly out of paper abstracts were picked up by the media for the apparent "bad reporting" in the popular press (" the only factor associated, with “spin” in the press release was “spin” in the article abstract conclusions"). The SGU spoke a lot about the topic, but only glossed over the actual paper content.

      The paper is at here .

      Yavchitz A, Boutron I, Bafeta A, Marroun I, Charles P, et al. (2012) Misrepresentation of Randomized Controlled Trials in Press Releases and News Coverage: A Cohort Study. PLoS Med 9(9): e1001308. doi:10.1371/journal.pmed.1001308

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  5. A few weeks ago, I mentioned a recent article by Eugen Koonin entitled “Does the central dogma still stand?” and said that it appears that Koonin doesn’t understand the Central Dogma as defined by Crick ( http://sandwalk.blogspot.com/2012/09/james-shapiro-claims-credit-for.html). Here is a quote from Koonin’s paper:

    ”the Central Dogma of molecular biology is invalid as an "absolute‟ principle: transfer of information from proteins (and specifically from protein sequences) to the genome does exist”

    Larry replied: “Koonin understands perfectly well what the Central Dogma of Molecular Biology means” and he went on to write a post about Koonin’s view ( http://sandwalk.blogspot.com/2012/09/does-central-dogma-still-stand.html.

    Here is how Larry concluded this post:
    “However, if people like Eugene Koonin are so bothered by the Central Dogma that they want to quibble over issues like this then maybe we should stop talking about it altogether. The Central Dogma may have outlived its usefulness.”

    I could not believe that Laurence A. Moran, the gate keeper of the Central Dogma of Molecular Biology, was ready to give up on a remarkable historical and conceptual landmark in molecular biology because a scientist, who he greatly admires, apparently, misunderstood the Central Dogma as defined by Crick.

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    1. I could not believe that (Larry) ... was ready to give up on a remarkable historical and conceptual landmark in molecular biology because a scientist, who he greatly admires, apparently, misunderstood the Central Dogma as defined by Crick.

      Eugene Koonin understands the correct version of the Central Dogma. He uses the version defined by Francis Crick. Koonin thinks the Central Dogma has been refuted by prions.

      That's just useless quibbling but if others like Koonin believes it's important then perhaps the correct version of the Central Dogma has outlived its purpose.

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    2. The idea that the Central Dogma has been refuted by prions (which, BTW, nobody knows what they are; see: http://www.nature.com/nature/journal/v470/n7335/full/nature09768.html), has been tossed around for decades by scientists in the prion field. So, there is no novelty there, at least not enough to publish yet another paper!

      However, there is plenty of ‘novelty’ in other ideas about the Central Dogma that were brought forward by Koonin, as described in the following 2 quotes:

      “The Central Dogma was conjured by Francis Crick in response to the discovery of reverse transcription, when it became clear that the RNA to DNA information transfer was an integral part of the life cycle of retro-transcribing genetic elements”

      ”the Central Dogma of molecular biology is invalid as an "absolute‟ principle: transfer of information from proteins (and specifically from protein sequences) to the genome does exist”

      So, apparently, Koonin believes that “The Central Dogma was conjured by Francis Crick in response to the discovery of reverse transcription”. Obviously, that is incorrect; as I previously mentioned, it seems that this author was not aware of Crick’s 1958 paper about the Central Dogma, which he did not cite.

      Second, Koonin states that the “transfer of information from proteins (and specifically from protein sequences) to the genome does exist”. This seems to be also flagrantly incorrect!

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    3. Incidentally, I found a very recent comment by Koonin on an issue very close to one of Larry’s strongest scientific believes: that on ‘directed mutagenesis.’

      In the comments section of a recent paper by Arlin Stoltzfus published in Biology Direct (http://www.biology-direct.com/content/pdf/1745-6150-7-35.pdf), Koonin says:

      ”It is clear now that a variety of mechanisms exist for directing mutations to specific targets that are relevant for adaptation under the given conditions”

      Maybe Larry can explain, or even write a post on it! (Parenthetically, I’m with Koonin on this one!)

      Also Larry and other Sandwalk readers might want to know that Sandwalk was cited in a comment on the same paper by evolutionist Peter Gogarten who said:

      “Other earlier writings by Arlin Stoltzfus that I highly enjoyed reading were the guest blogs he wrote for Larry Moran's Sandwalk blog [65], analyzing the forces that shaped today's perception of the modern synthesis and neo-Darwinism"

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    4. What comments? Your link goes to the BioMed Central pdf, which has no comments. When I go to the article page at the online journal site, it says "No comments have yet been made on this article."

      Better yet, why not link to, or at least describe, the evidence that you think supports directed mutation. (Or information flowing from protein sequences to the genome.)

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    5. It is in the .pdf. They posted the comments from peer-review round.

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    6. The Other Jim, thanks for the answering the questions about the location of the comments I quoted.

      @qetzal: We have discussed at large ‘directed mutations’ here at Sandwalk, please see:

      http://sandwalk.blogspot.com/2012/05/on-difference-between-evolutionary.html

      http://sandwalk.blogspot.com/2012/09/james-shapiro-claims-credit-for.html

      http://sandwalk.blogspot.com/2012/09/boudry-vs-plantinga.html

      If you read these comments, unfortunately, you’ll run into some of the most shocking words written by a scientists “I'm not interested in discussing that paper”. And, I’m sorry to say that this scientist was Larry, our host.

      The scientific paper under discussion was entitled ‘Transcription-associated mutation in Bacillus subtilis cells under stress” ( http://www.ncbi.nlm.nih.gov/pubmed/20435731) which was published in the reputable Journal of Bacteriology.

      Because the paper presented results that conflicted with his views about ‘directed mutations,’ Larry refused to address it. Like many other modern scientists , Larry has learned that the best way to deal with inconvenient questions or issues is not by rationally addressing or criticizing hem, which would bring them into discussion, but by pretending that they don’t exist, which is indeed the most efficient way of keeping ideas or the truth silent!

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    7. qetzal says: ”(Or information flowing from protein sequences to the genome)”

      I did not say that, Koonin said it, and here is the quote:

      ”the Central Dogma of molecular biology is invalid as an "absolute‟ principle: transfer of information from proteins (and specifically from protein sequences) to the genome does exist”

      Larry keeps preaching to us that ”Eugene Koonin understands the correct version of the Central Dogma”. We are all curious how does he explain Koonin’s statement that the information is transferred from proteins, specifically from protein sequences, to the genome?

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  6. setting aside the not insignificant detail that the central dogma still stands, why do people act as if discovering exceptions to rules, or new principles that overturn or modify older ones, is remarkable? This is of course how the scientific process would be expected to perform.

    In the above example the scientists have just embarrassed themselves. As for ID advocates, their goal, as with most religious conservatives, is to convince their non-scientific audiences that there is something inherently untrustworthy about science.

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  7. I note that some version of the phrase "should have learned as undergrads" comes up very often. My own experience which doesn't seem to terribly dissimilar suggests that the rush to get everybody to do a research experience i.e. the ultimate in student centered learning may be contributing to this phenomena. One undoubtedly learns a lot, but I can safely say looking back that with respect to understanding basic concepts I was in way over my head on every single project I ever started practically(with the possible exception of grad school). I had my first joint publication before I even had any college level biology in the most extreme case.

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  8. "changes occurring in somatic cells cannot be inherited (also known as Lamarckian evolution)"

    Maybe when they state that this idea has been overthrown, the authors are thinking about plants and applying inappropriate terminology? In flowering plants a mutation in a shoot meristem cell results in stem and leaf cells with the same mutation, and can lead to ovules and pollen carrying that mutation. Of course, the somatic / germline distinction is not applicable in plants.

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