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An even bigger question: why is DNA/RNA always expressed in the same way? I.e. the codon->aminoacid table is constant for all living things. I always found this
by H8crilA 7y ago
An even bigger question: why is DNA/RNA always expressed in the same way? I.e. the codon->aminoacid table is constant for all living things. I always found this very puzzling. Of course, the easiest explanation is that life really did start from a single cell. But it sounds unlikely that a) there really was that single origin cell, and not a few that popped up around the same time (on a geological scale), and b) no organism has drifted in the millions of years of evolution.
- Sniffnoy 7y agoVariants on the genetic code are known to exist: https://en.wikipedia.org/wiki/Genetic_code#Alternative_genetic_codes https://en.wikipedia.org/wiki/Genetic_code#Alternative_genet... I don't think there are any known to be radically different. Note that it's possible that life arose several times but only the lineage of that one cell survived, perhaps? In any case, it's not like there's been no variation. Now, here's a mystery (AFAIK): Just where is the genetic code stored? I seem to recall reading an article a while back about how while this seems like an easy question it's actually not known. I can't seem to find it at the moment, though. Anyone know more about this?
- fabian2k 7y agoThe mapping between base triplets and amino acids is encoded in the tRNAs. And the tRNAs themselves are of course again encoded in the DNA sequences used to produce them.
- Sniffnoy 7y agoI mean, that's the obvious answer, but I recall reading a thing about why it wasn't actually that simple, how swapping out the tRNAs didn't actually have the effect you would expect. Like, obviously the anticodons match the codons, no problem there, but there was some complicated confusing thing about how the rest of the tRNA matched the amino acid. Trying to find it. Hoping someone knows what I'm talking about.
- learnstats2 7y agoPresumably, biology has a lot of safeguarding to prevent modified transfer-RNA from being functional. In terms of potential errors in gene expression, the genetic code is rarely discussed as a potential source of error.
- Reelin 7y agoNot to be "that guy", but actually, it is. (https://elifesciences.org/articles/09945 https://elifesciences.org/articles/09945) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026258/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026258/) It's just difficult to study for various technical reasons related to how we sequence it. Sometime the mistranslation is even intentional! (https://www.ncbi.nlm.nih.gov/pubmed/25220850 https://www.ncbi.nlm.nih.gov/pubmed/25220850) As you mentioned though, there are also quite a few safeguards. * tRNA synthetase example: https://www.ncbi.nlm.nih.gov/pubmed/27226603 https://www.ncbi.nlm.nih.gov/pubmed/27226603 * trans-editing factor example: https://www.ncbi.nlm.nih.gov/pubmed/28737471 https://www.ncbi.nlm.nih.gov/pubmed/28737471 Damaged tRNA is even repaired (a bit, sometimes). (https://www.ncbi.nlm.nih.gov/pubmed/28901837 https://www.ncbi.nlm.nih.gov/pubmed/28901837) From an interesting (2018) review of tRNA in general (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103721/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103721/): > Surprisingly, a perfect proteome is not a pre-requisite for cellular viability even in the context of human cells. Lant et al. demonstrated that a single tRNA mutant can lead to significant mistranslation in human cells [17]. This was accomplished by expressing an Ala accepting tRNAPro G3:U70 variant in HEK 293 cells. The authors visualized a rate of ~ 3% mistranslation using a novel green fluorescent protein (D129P) reporter that fluoresces in response to mistranslation at proline codons. In contrast to previous studies in yeast [18], human cells in culture did not mount a detectable heat-shock response and tolerated the mistranslation without apparent impact on cell viability.
- klmr 7y agoThe eLife paper you link to discusses errors in RNA synthesis (transcription), not in tRNA-dependent protein synthesis (translation). The abstract mentions “translation”, but only as an amplifier of transcription errors: each mRNA transcript is translated into proteins thousandfold, so every error in a single mRNA molecule will be present in thousands of protein molecules. Translation errors also exist, and some people hypothesise that there is selective pressure on protein-coding genes to reduce this source of errors by selecting codons in a way that reduces the error rate (potentially by slowing down the polymerase). This results in something known as “codon bias” but so far there is no good evidence that codon bias has an actual effect on error rate (it does have an effect on correct protein folding), or is selected for (http://dx.doi.org/10.7554/eLife.27344 http://dx.doi.org/10.7554/eLife.27344, http://dx.doi.org/10.1371/journal.pgen.1006024 http://dx.doi.org/10.1371/journal.pgen.1006024).
- twic 7y agoI'd say it's encoded in the combination of the tRNAs and the aminoacyl-tRNA synthetases, which load the appropriate amino acids on to the tRNAs. There's nothing in the tRNAs themselves which picks out a specific amino acid - that happens because the synthetases recognise specific amino acids and specific tRNAs. The synthetases are also encoded in DNA, so the fundamental point, that the code is encoded in DNA, stands.
- Sniffnoy 7y agoAha! Thanks, hopefully with that search term I can maybe find what I was thinking of. :)
- dosy 7y agois that correct? I seem to remember a biochem class noting there are exceptions, and depending on conditions or species codons can be transcribed to different AA. For the first question, isn't this related to the types of AA that can bind to transcriptase?
- ozy 7y agoIt isn't: https://en.wikipedia.org/wiki/List_of_genetic_codes https://en.wikipedia.org/wiki/List_of_genetic_codes On the other hand, once a certain layer of functionality exists, and starts being used to build on top of, that layer will resist change, because any variation will throw off so many higher level processes it's unlikely to be viable.
- yourapostasy 7y agoThe ultimate technical debt if there ever was one for our species. An "oopsie" at this layer would be pretty insanely difficult to architect and engineer around.
- phkahler 7y agoSelenocysteine is a really strange one.
- deleted 7y ago[deleted]
- teekert 7y agoThis small snippet from Wikipedia claims that DNA/RNA is not always "expressed in the same way" and that bacteria en eukaryotes have a different (albeit related) amino acid for AUG (Methionine vs. N-formylmethionine). So those claims here and in the article (even the title) are not completely true. _Encoding_ Methionine is one of only two amino acids encoded by a single codon (AUG) in the standard genetic code (tryptophan, encoded by UGG, is the other). In reflection to the evolutionary origin of its codon, the other AUN codons encode isoleucine, which is also a hydrophobic amino acid. In the mitochondrial genome of several organisms, including metazoa and yeast, the codon AUA also encodes for methionine. In the standard genetic code AUA codes for isoleucine and the respective tRNA (ileX in Escherichia coli) uses the unusual base lysidine (bacteria) or agmatine (archaea) to discriminate against AUG.[15][16] The methionine codon AUG is also the most common start codon. A "Start" codon is message for a ribosome that signals the initiation of protein translation from mRNA when the AUG codon is in a Kozak consensus sequence. As a consequence, methionine is often incorporated into the N-terminal position of proteins in eukaryotes and archaea during translation, although it can be removed by post-translational modification. In bacteria, the derivative N-formylmethionine is used as the initial amino acid. [0] [0] https://en.wikipedia.org/wiki/Methionine https://en.wikipedia.org/wiki/Methionine
- jayd16 7y agoPerhaps there's a first mover advantage such that any new gene system just can't compete with established life.
- magicalhippo 7y agoIt's not so much first mover advantage I think as established life having had tons of time to optimize. Tierra[1] illustrates how any new system has to be much better than the established to have any chance of surviving. [1]: https://en.wikipedia.org/wiki/Tierra_(computer_simulation) https://en.wikipedia.org/wiki/Tierra_(computer_simulation)
- earenndil 7y ago> it sounds unlikely that a) there really was that single origin cell, and not a few that popped up around the same time (on a geological scale) Why? Life happens rarely enough; even in the 'optimal' conditions of the primordial soup, it's still a pretty miraculous occurrence for a cell to spontaneously form. Then consider this: - The first cell was probably not 'good' at surviving, even in those conditions. It probably sucked at it, and was just barely good enough at doing it to reproduce a little and evolve a little. - So, a cell which is actually good at surviving is pretty much guaranteed not to form spontaneously. Meanwhile, the lineage of the first (shitty) one has evolved to be pretty damn good at it. - If a new cell tries to form, even if it's better at surviving than the Original cell, it'll probably get instantly outcompeted by its progeny. Voila, single ancestor cell. > b) no organism has drifted in the millions of years of evolution. Why should they? There's no pressure to.
- magicalhippo 7y agoI read long ago about someone doing computer simulations, finding that the current table is near optimal when it comes to error resilience (against mutations etc) as well as encoding efficiency IIRC. This would answer why most are using it now. If other cells uses a different mapping that's less optimal, they'll have a harder time to reproduce, and thus lose out over time.
- plushpuffin 7y agoThat was in the April 2004 issue of Scientific American: Evolution Encoded. https://www.jstor.org/stable/26047680?seq=1#page_scan_tab_contents https://www.jstor.org/stable/26047680?seq=1#page_scan_tab_co... https://wps.prenhall.com/wps/media/objects/12330/12626747/myanthropologylibrary/PDF/BA_SCIAM_15_Freed_Hurst_562.pdf https://wps.prenhall.com/wps/media/objects/12330/12626747/my...
- magicalhippo 7y agoThat would be it. Thanks for digging it up!
- rtkwe 7y agoYeah I think the answer is pretty clear why there's one. It was slightly better than the others in some ways like error resistance (important on a young, ie recently formed, where there's no atmosphere to protect from UV and other comic radiation) and then it just out competed. It's easy to forget just how long it took to go from single celled life (4000 MYA) to multi celled life (~2100 MYA, first fossil evidence at least). That's almost 2 billion years for different versions of DNA/RNA/Amino acids to be tried and tested with almost no chance that we'd find fossil evidence of it. (Not even sure if you could tell from a fossil at all honestly)
- PeterisP 7y agoIIRC the standard argument against "not a few that popped up around the same time (on a geological scale)" is that geological scale is so much, much longer than biological scale, that the time between two events that would be "around the same time (on a geological scale)" is sufficient for that single cell to multiply in immense amounts, colonize the whole of world's oceans, evolve significantly, and (most importantly) eat up all the easily available resources that allowed it to form. If we look at the 'primordial soup' theory, it's about concentrations of aminoacids that can accumulate only if life is not present - once the first life spreads through the oceans, it'll colonize and consume every location that's sufficiently rich for new life to spawn.
- abcc8 7y agoThe codon->amino acid table is not always expressed in the same way within human cells. Mitochondria utilize different codons for the same amino acids compared to the nuclear genome.
- king07828 7y agoFascinating. Multiple different DNA based instruction set architectures. https://en.wikipedia.org/wiki/Human_mitochondrial_genetics https://en.wikipedia.org/wiki/Human_mitochondrial_genetics Genetic Code Variants For most organisms the "stop codons" are "UAA", "UAG", and "UGA". In vertebrate mitochondria "AGA" and "AGG" are also stop codons, but not "UGA", which codes for tryptophan instead. "AUA" codes for isoleucine in most organisms but for methionine in vertebrate mitochondrial mRNA. wikipedia cites to https://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi https://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi?
- petjuh 7y agohttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894784/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894784/
- klmr 7y ago> But it sounds unlikely that a) there really was that single origin cell This is just a fact. All life that we know of has the same origin. Common descent is a core tenet, and one of the best established facts, of modern biology (https://doi.org/10.1038%2Fnature09014 https://doi.org/10.1038%2Fnature09014). For there to have been multiple distinct ancestors, we would need to see some relevant differences in the core machinery of life. And the fact is that, despite minor variations, we simply don’t see any. The odds of there being multiple distinct ancestors is astronomical, and would fundamentally impact our understanding of modern biology. > and b) no organism has drifted in the millions of years of evolution Organisms have drifted. That’s what evolution is. But evolution plays by rules, it can’t just change things willy-nilly. Changes to the core machinery would presumably either break it outright, or be so strongly detrimental as to be purified away almost immediately. Of course many genetic changes are deleterious to some extent but most effects can either be buffered for a short time because they are minor, or they confer some other advantage. In the core machinery of the cell this is much (!) less tolerated because even tiny chemical inefficiencies would immediately be amplified millionfold. Odds are, the DNA/RNA core machinery of all life sits in a steep local optimum. It’s not necessarily a global optimum but it’s essentially impossible to evolve out of because any individual change, or even a handful of coincidental changes, would leave the organism a lot worse off.
- naringas 7y ago> Common descent is a core tenet but that doesn't mean it's been proven through experimentation, does it? isn't it just an assumption? what if there's something akin to mathematical uniqueness in the mechanics of the core machinery? I mean it in the sense that it's either the way it is, or it's not really viable over a long enough period of time? such that it could have multiple origins which all nontheless converge into the same core mechanism?
- klmr 7y ago> but that doesn't mean it's been proven through experimentation, does it? isn't it just an assumption? It’s not an assumption, it’s backed up by excellent evidence — see the paper I linked. > what if there's something akin to mathematical uniqueness in the mechanics of the core machinery? Well that’s clearly not the case, we can trivially (…) design self-replicating machines that have completely different mechanics, as a thought experiment. More to the point, we can change parts of the machinery. For instance, we can take the universal genetic code and, with effort, change it into something completely different (by just swapping all codons around). The result is just as viable, but doesn’t exist in nature. In fact, the observed universality of the genetic code, in itself, is already seen as sufficient evidence for common descent (and then some).
- gnulinux 7y ago> But it sounds unlikely that a) there really was that single origin cell, and not a few that popped up around the same time (on a geological scale) This is not a necessity. It is entirely possible life on earth was formed multiple times, completely independently and our lineage simply out-competed other sort(s) of life; and somehow we lost the evidence of it, or couldn't find it yet. As it's suggested by other comments, it's a well established fact that the life we know of share the same single origin (this organism(s?) is called the "Last universal common ancestor" or LUCA [1]); but that doesn't mean there has been a single sort of life our lineage ever interacted with, it just means our lineage was the only good-enough life for the conditions on earth for most of the geological periods. [1] https://en.wikipedia.org/wiki/Last_universal_common_ancestor https://en.wikipedia.org/wiki/Last_universal_common_ancestor
- cc439 7y agoIf I had to relate this to an HN related topic, I'd say this is closest to the theory of "technical debt". The further your code base moves away from the origin, the more difficult it is to address issues in the foundational code. Fudging around with the basic building blocks of life is extremely risky in an evolutionary perspective, gains can be made but they are going to be smaller (less advantageous) than gains possible by fudging around with top level code. By making base level changes, you effectively halt top level change until everything is proved out. By the time a base level change would have stabilized and the gains realized, the more nimble organisms making top level changes will have long since outcompeted the base changer into oblivion.