Francis Crick's "Central Dogma" was misunderstood
asimov.press
asimov.press
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.
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.
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.
> 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.
In that regard, I feel this is particularly relevant:
"During an organism’s life, environmental conditions cause certain genes to get switched on or off. This often occurs through a process known as methylation, in which the cell adds a methyl group to a cytosine base in a DNA sequence. As a result, the cell no longer transcribes the gene.
"These effects occur most frequently in somatic cells — the cells that make up the body of the organism. If epigenetic marks occur in sex cells [however], they are wiped clean prior to egg and sperm formation. Then, once the sperm and eggs have fully formed, methylation patterns are re-established in each type of cell, meaning that the acquired genetic regulation is reset to baseline in the offspring."
I would guess that, in the ordinary cases of cell division, the replication of methylation is, on balance, desirable, and that it probably requires an additional mechanism beyond minimal DNA base-sequence replication. In that case, its near-absence specifically within gamete production seems likely to be significant. The cases where methylation persists through generations should not be ignored, and neither should the existence of a mechanism that apparently exists to prevent (or at least constrain) it (or a mechanism to
> “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.
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?
How can DNA 'get' more information if not from the proteins interactions with its environment?
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.
Is this regarding Rosalind Franklin's data?
Not really taking credit or misunderstanding the work of his betters.
> 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.
Many many exceptions, but this is the main causal flow.
...did you read it?
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.)
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_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!
I don't understand how you arrive at this — while it's true they almost certainly do not "corrupt your DNA", the reasons have nothing to do with the central dogma as Crick conceived it, since information flow from RNA to DNA is not addressed by it.
'while it's true they almost certainly do not "corrupt your DNA"' I second this