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Francis Crick's "Central Dogma" was misunderstood
- moomin 2y agoSurely prion diseases are an example of protein to protein, which the article specifically says was part of the CD? I’m not unhappy with the tone of the article suggesting that Watson, yet again, vastly misunderstood the work of his betters while taking credit for it.
- benlivengood 2y agoI think if prions were considered violations of CD then enzymes or at least ribosomes would be considered to violate CD as well.
- IWeldMelons 2y agoribosomes are not proteins though.
- dekhn 2y ago(to clarify: Ribosomes are composed of mostly protein; they are protein/RNA complexes in which the enzymatic functionality is implemented by RNA enzymes that are decorated with proteins that stabilize the complex, as well as increase its efficiency).
- birdiesanders 2y agoThe “dogma” is “information flow from proteins back to genetic material does not occur” not that proteins can’t transfer information. Regardless of considering “shape” as information or not, the transfer is not violating that statement, the information is fully trapped in the protein and not flowed back to DNA.
- lmm 2y agoThe article explicitly lists protein -> protein as one of the 3 prohibited information flows.
- spiritbear14 2y agothe article argues that prions do not facilitate the flow of information in the same way the Dogma states. They simply change the way the protein is folded, but not the amino acids in the structure. I disagree with this (I have papers in this field that say the opposite), but that is the argument.
- transcriptase 2y agoIt seems the articles purpose is less about what could best be described as dunking on what 10th graders are taught about molecular biology for simplicity’s sake, and more about discrediting Watson by reframing the past, and chipping away at his legacy because of… well, you know.
- throwbmw 2y agoWhat?
- jakubsuchy 2y agoBecause...you know...he stole the DNA discovery from Rosalind Franklin
- moomin 2y agoDon’t forget the eugenics. Dude did an awfully thorough job of trashing his own reputation.
- gopher_space 2y agoHanging your name on things has always been a double-edged sword in any context, but science is actively held back by cults of personality. Your contributions might be foundational, but your legacy is harmful.
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- 77pt77 2y ago> Watson, yet again, vastly misunderstood the work of his betters while taking credit for it. Is this regarding Rosalind Franklin's data?
- moomin 2y agoI mean, there’s that, there’s the eugenics stuff… with Watson it’s a bit of a target-rich environment.
- twic 2y agoAs the first figure says: > Information here means the sequence of the amino acid residues, or other sequences related to it. Prions do not transfer sequence information between proteins, so this is in keeping with Crick's idea. I've always assumed that Watson understood Crick's idea perfectly well, but used the simpler formulation because it was easier to communicate, while still being mostly accurate.
- robwwilliams 2y agoYes, that is highly likely. Most causality flows in the same direct—from DNA variants through RNA variants, through protein variance to differences in phenotypes. Many many exceptions, but this is the main causal flow.
- danparsonson 2y ago>...Specifically, prion proteins do not change the sequence of amino acids; they instead transmit their pathological shape to otherwise “healthy” proteins, causing them to misfold in the same way. Prion diseases do not alter the validity of the Central Dogma because they don’t alter any genetic sequences. ...did you read it?
- pknomad 2y agoUnfortunate nomenclature aside, this issue highlights the difference between models and reality in science and how students can take these models too literally and thus easily conflate the two in pedagogy. Here's an embarrassing story for me: I didn't realize (or at least didn't internalize) that not all cells in the human body conform to to the canonical image of the cell that we see in Biology textbooks (https://en.wikipedia.org/wiki/Cell_(biology)#/media/File:Celltypes.svg https://en.wikipedia.org/wiki/Cell_(biology)#/media/File:Cel...) until I finished oncology and embryology class in my senior year back in 2015. For example, erythrocytes (RBCs) don't have nucleus and mitochondria. Some hepatocytes even have more than 1 nucleus (polyploidy). I still don't know how I went through my cell biology class in sophomore year without understanding this. Maybe I missed the forest for the trees (curse you clathrin mediated endocytosis!)
- kridsdale1 2y agoMuscles also have more than one nucleus per cell, if you have strength trained. You can fast and diet and waste away all the protein and shrink them down, but the nuclei remain. Go in to a surge of calories, protein, (and optional androgenic hormone signaling) and the nuclei effectively parallel process transcription of mRNA in the ribosomes for regeneration of the proteins from amino acids and re-bulking up of the cells and your strength. This, (along with neural adaption) is what we are taking about when we reference “muscle memory”. It’s a steep hill to train the first time and multiply the nuclei, but once you have them, you have them for life, and subsequent re-strengthening efforts will be far easier. I’ve gone through this myself and it’s pretty shocking. It took me X years to achieve Y kilograms barbell whatever movement. A diet or lack of training for a year and I can only do Y/2. But if I eat a ton, I can be back to Y or higher in a few months.
- renewiltord 2y agoThat’s the mechanism? It makes sense. It was trivial for me to return to my strength after an accident that left me hobbled for months but progress beyond is just as hard as originally. Cool.
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- exmadscientist 2y ago...well that makes a lot more sense now. Flashing back to my undergrad biology class, I honestly never understood what was so important about the "central dogma" or why it was so important to spend so much time on. Now, reading its origin story, it is immediately apparent why it's interesting and such an important feature of life to understand. (Tangent: anyone who complained about mRNA vaccines "corrupting your DNA" fell afoul of exactly what the central dogma is about.) More broadly, it is fascinating to see how often this happens. So many ideas that are spread or taught in their "modern form" are trite or difficult or just disconnected. And then you see them in their original place, often in the original discoverer's words... and it's immediately obvious what they really mean and why they're so important. (Another example: Einstein's (special) theory of relativity. Read his original papers! They're short and explain everything!) I'd suggest the solution is just reading more primary source material, but unfortunately the opposite is also true: plenty of stuff is illegible in its original form, too. (Maxwell's formulation of Maxwell's equations comes to mind here.)
- kleton 2y agoIt is difficult to entirely avoid contamination by DNA. https://x.com/p_j_buckhaults/status/1861083163868672204 https://x.com/p_j_buckhaults/status/1861083163868672204
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- Mathnerd314 2y agoOne way to look at it is that most college textbooks are bad. They are written by one person, who has limited time, and limited understanding. And then you have a teacher who knows even less than the textbook, trying to explain the textbook. In contrast, Wikipedia editors have all the time they care to spend on the subject (which is a lot!). They often reproduce the original discoverer's words, when appropriate. E.g., https://en.wikipedia.org/wiki/Central_dogma_of_molecular_biology https://en.wikipedia.org/wiki/Central_dogma_of_molecular_bio... uses Crick's words. Whereas in the case of Maxwell, the formulation "is credited to Oliver Heaviside". Long story short: Wikipedia has the best explanations, and if you don't think so then fix it!
- raldi 2y agoI don’t understand how “Crick’s attempt to break the central dogma” … “relied upon the fact that the genetic code is redundant.” The article doesn’t seem to present any explanation of how his argument supposedly relied on that.
- lupire 2y agoI think it was a bad argument, perhaps due to weakness in Crick's knowledge of information science. The argument goes like this; Suppose you built a library of chemical reactions, to generate a DNA codon from an amino acid, and did this for all of the different amino acids. Since two different DNA sequences comple to the same protein, you could take sequence A, perform transcription and generate a protein P, and then construct a different DNA sequence B. Thus we have "genetic information" extracted from a protein and stored in DNA, violating the Dogma... in an extremely cheesy way, since it's obviously the same "information" you had at the start, just encoded differently, and also it's not different in any meaningful sense from doing the same reverse engineering on non-logically-redundant DNA.
- spiritbear14 2y agoI think the idea is that this different codon sequence "may" be able to be used by the biological organism in a as yet to be discovered way. So, it wouldn't be useful in producing more proteins but may be able to affect the cell in some other way. I've never heard of anything like that though and the redundant codons is probably just the most thermodynamically efficient route to protein production. Interesting thought though
- asdff 2y agoRedundant codons allows for more fidelity in signal. If you notice for most codons in the codon table the third base in the codon can mutate and still encode for the same amino acid. Now that position in the DNA is more tolerant of receiving a mutation to the point we call it a silent mutation if one is there.
- TeMPOraL 2y ago
- spiritbear14 2y agoHere is an argument against the CD. We know that DNA changes overtime due indirectly from environmental conditions through evolutionary natural selection. So, why is this not an argument for the reversed direction of information?
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- infradig 2y agoThe proteins don't directly change the DNA via information transfer, that's not how natural selection works.
- asdff 2y agoPlenty of protein work with DNA in the cell. Repair protein could screw up the DNA repair, now you pass that screw up on to the daughter cells.
- spiritbear14 2y agoNot directly, but in a very long round about way they do. Like if I have a mutation that is evolutionarily positive, the only way that helps me pass on my DNA is through the expression of the proteins, without them I could not do anything. The proteins, and their interactions with the environment, creates new information that indirectly results in a evolutionary pressure on the DNA and at a population level can change it. How can DNA 'get' more information if not from the proteins interactions with its environment?
- andrewflnr 2y agoBecause having a vague, highly indirect, unpredictable and generally unreliable influence on genetic information is not the same as transmitting or copying it in day to day operation. Not even close, not even comparable for the purpose of answering measurable questions. The CD is not, and was never intended to be, an all-encompassing metaphysical invariant, it's an observation about biochemistry.
- globalnode 2y agonot a biologist, but if we have a bunch of redundant dna (aka genes) that get activated/deactivated based on our environment, would that "state" be transferred to children? or do children get a blank slate of parental dna? also, what causes genes to activate or deactivate? if proteins have any impact on this then there is information flow in the reverse direction, no?
- spiritbear14 2y agoTo answer the second question, the Central Dogma is interested in permanent changes at each stage, so the proteins can change the way DNA is expressed, but it cannot change the DNA sequence itself.
- globalnode 2y agothank you
- wiml 2y agoI think there are multiple mechanisms by which genes "activate" and "deactivate", but one of them is methylation, which can to some extent be passed to offspring: this is studied as part of "epigenetics".
- panabee 2y agoProteins can cause DNA alterations via chromosomal translocations. If these occur in germ cells, the new sequences may transmit permanently to future generations. Depending on the definition of "information transfer" and the willingness to consider methylation as information transfer, how would the Central Dogma view protein-induced chromosomal translocations?
- asdff 2y agoThe central dogma doesn’t consider them because it was developed before they were widely known. Its still useful because we don’t cover these topics that deviate from the central dogma terribly thoroughly until grad school where you might specialize in it, and finally read the corpus of seminal papers in that line of biology.
- galaxyLogic 2y agoIsn't this about the same as using a compiler to produce binary code from a high-level language? The code in the high-level language determines the binary executable code output. But the binary output cannot produce the code in the high-level language. Of course we can build "de-assmeblers" etc. that do somehing like that for us, but nature does nto have de-assmebhlers.
- pfisherman 2y ago> The most significant part of Crick’s idea — and the part that Watson ignored in his oversimplification — was that there are three flows of information that cannot occur, due both to lack of experimental evidence and any plausible biochemical mechanisms. These were protein → protein, protein → RNA and, above all, protein → DNA. These are categorically untrue. Post translational modification of proteins (by proteins) is a thing. Post transcriptional modification of RNAs (by proteins) is a thing. Transposition of DNA sequences (by proteins) is a thing.
- robwwilliams 2y agoThese exceptions covered toward the end of the article. The core claim by Crick boils down to “no reverse translation”.
- sparsely 2y agoI think this is a much clearer expression of the claim than the commonly given one.
- dreamcompiler 2y ago> Post translational modification of proteins (by proteins) is a thing. Yes prions are real but the article points out that prions modify the way other, already-existing proteins fold. Prions do not create new proteins nor do they change the amino acid sequences of other proteins, which means prions don't violate the dogma. The article addresses your other points as well.
- sparsely 2y agoFolding is clearly a form of information transfer though (and proteins are deeply involved in folding other proteins, even outside of the prion case). As stated in the screenshot it is fine "information here means the sequence of amino acid residues..." but that's a much narrower definition than is commonly communicated. Proteins also do change the amino acid sequences of other proteins - they cleave them! The results of the cleavage are then important for cell biology, and although it seems plausible that the the results could have traditional "protein" style functions, e.g. as an enzyme, I not sure this is ever actually the case. But the end result is still that the rule has to be understood very narrowly.
- cromulent 2y agoI re-listened to Malcolm Gladwell's podcast episode about Nobel prize winning Howard Temin on the weekend. According to his student: > “At one point, Howard Temin wrote Francis Crick, Sir Francis Crick, Nobel Prize winner of Watson and Crick, the co-discoverers of DNA, the authors of the central dogma itself. Temin writes Crick a letter, gently suggesting that an amendment to the central dogma might be in order. Crick writes back: "I'm sure you think this is true, but you must realize you are wrong". https://www.pushkin.fm/podcasts/revisionist-history/the-obscure-virus-club https://www.pushkin.fm/podcasts/revisionist-history/the-obsc...
- Myrmornis 2y ago> profoundly misleading. > Watson’s reductive and erroneous presentation. These descriptions are silly, and a huge exaggeration. The traditional succinct formulation (from Watson) DNA => RNA => Protein is used in an educational context (whether of the general public or students). As such it does a great job! If students can get and retain that idea, then the educator is winning. And if the student goes further into molecular biology they may discover that reverse transcription exists. Great. But simple-to-understand formulations that capture the key idea are pedagogically essential, and the attacks in this article are completely unnecessary. It's easy to wonder whether they are irrational, i.e. sociopolitically motivated by (perfectly reasonable) distaste for Watson's (deeply unpleasant) comments made later in life, and they lessen the attraction of the author's forthcoming biography of Crick.
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