Unfortunate 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: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!)
Muscles 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.
That’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.
It’s always refreshing for me to hear share what they did _not_ know, especially when it’s seems like “something obvious” that they absolutely “should” have known. Thanks for being honest and open - I can personally really relate to this anecdote, and also in the context of biology, genetics, etc.
Surely it's obvious even before finishing high school that everything you are taught in science is at best a partial truth and that this is especially true when you are young and inexperienced. Newton's laws are an approximation to reality at low velocities so we learnt them knowing that it was not the whole story but was good enough for a huge amount of work. In my Applied Physics degree (50 years ago) we didn't do General Relativity, there simply wasn't time to learn the relevant mathematics as well as everything else so we made do with Special Relativity. And so on.
I do agree though that some teachers do give the impression that what they tell you is the whole truth, perhaps I was lucky in mine being mostly more enlightened.
> For example, erythrocytes (RBCs) don't have nucleus and mitochondria.
They are less of an outlier when you find out that they start out with a nucleus but pinch it off and let white blood cells eat it when they near maturity.
Yep! I vaguely remember my professor mentioning about this in my Immunology class when we were on the topic of recognizing self vs non-self. Something about MHC1 vs CD47 on RBCs. It's been a while. Fascinating stuff!
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.
> 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.
> 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.
Folding 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.
In the diagram/text description it is specifically referring to replication, in the sense of transmitting genetic information to daughter cells. In that sense there is no protein-protein transfer; no means of copying one protein or rebuilding nucleic acids from the amino acid sequence.
I 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".
Proteins 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?
The 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.
what Crick means, I believe, is that since multiple codons can code for a single amino acid the information or entropy in that set of codons is larger than the information transferred to the protein creating a many-to-one interaction. This means that you could, in principle, create an RNA sequence 'A' that codes for the same protein as another sequence 'B', but they are discretely different implying that this difference could be exploited to send different information back from proteins to this different RNA sequence. Kinda a reach in my opinion and not really important as proving you could do that doesn't bring us any closer to understanding what nature actually does. I guess the most interesting result with this research is analyzing the thermodynamics of this reverse interaction as an argument as to why nature has not evolved a way to do this.
Codons for the same amino acid can have very different efficiencies due to use of different tRNAs. And tRNA abundance varies across organelles (mitochondria), cells, and organs. It is not just protein sequence but also protein abundance and translational progressivity/speed/efficiency and completeness. Reverse translation would not recover these aspects.
I 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.
I 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
Same protein P is coded by two different sequences, A and B. The "redundancy" observation is just saying that when you find some P molecules in the organism, you can't tell which were coded by A and which by B - that information is, literally, lost in translation. Yes, it's not really lost - it's smeared over the "global state", as DNA sequences are physical objects and A and B have slightly different resource costs, but that's still far from being able to modify DNA based on information from proteins.
FWIW, "redundancy" does have some different interesting functions in nature. Sequences like "AAAA" "ABAB" and "BBBB" are (in this example) equivalent under normal read, but if you shift the reading window one nucleotide to the left or right, those two sequences could code for something else entirely. AFAIK some bacteria exploit that. But again, this is still not a protein->DNA information transfer.
Isn'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.
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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!)
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.
https://en.wikipedia.org/wiki/Myogenesis
I do agree though that some teachers do give the impression that what they tell you is the whole truth, perhaps I was lucky in mine being mostly more enlightened.
They are less of an outlier when you find out that they start out with a nucleus but pinch it off and let white blood cells eat it when they near maturity.
https://wi.mit.edu/news/how-red-blood-cells-nuke-their-nucle...
They also shed their mitochondria at about the same time. Both make more room for hemoglobin, optimizing them for oxygen transport.
> 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.
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.
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.
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.
> “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-obsc...
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?
The article doesn’t seem to present any explanation of how his argument supposedly relied on that.
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.
Same protein P is coded by two different sequences, A and B. The "redundancy" observation is just saying that when you find some P molecules in the organism, you can't tell which were coded by A and which by B - that information is, literally, lost in translation. Yes, it's not really lost - it's smeared over the "global state", as DNA sequences are physical objects and A and B have slightly different resource costs, but that's still far from being able to modify DNA based on information from proteins.
FWIW, "redundancy" does have some different interesting functions in nature. Sequences like "AAAA" "ABAB" and "BBBB" are (in this example) equivalent under normal read, but if you shift the reading window one nucleotide to the left or right, those two sequences could code for something else entirely. AFAIK some bacteria exploit that. But again, this is still not a protein->DNA information transfer.
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.
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