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Researchers have identified a new DNA structure called the i-motif inside cells
- quark33 9y agoI'm curious what sort of implications this will have for hereditary disease gene research (Cancer, Alzheimers, etc).
- jeppz 9y agoThe problem right now is that "has only been witnessed in vitro – that is, under artificial conditions in the laboratory, and not inside cells." which means it may not even exist in our bodies.
- alexholehouse 9y agoBut this is literally the entire point of the this paper. The sentence you just pasted was the the previous state of the art, this paper makes the point that they have now imaged them in cells (using i-motif specific antibodies).
- subroutine 9y ago'in vitro' can mean 'in cells in a dish'. I think the previous state of the art was 'unsure if these exist in living cells' (could be wrong, but id be surprised if they did this exp in vivo). edit based on your comment above you probably have the paper and are in a better position to comment on this. I defer to op.
- alexholehouse 9y agoYeah agreed (what in vitro means to different people is a whole other conversation :-P), but that sentence makes it pretty clear that by in vitro they mean not in cells (because it says, "and not inside cells"). Agreed, of course, that this doesn't necessarily mean it happens in cells in an organism (though in the authors' defense they do examine three different cell lines). Edit: For clarity - all the in cell work is cultured cell lines and not cells taken from an animal model or in situ imaging. Literally my only point was that 'this might not matter for biology because we've not even seen it in cells' is no longer true. It still might not matter for biology though!
- subroutine 9y agoSeems like these "i-motifs" form transiently during transcription. If they are making the argument these motifs exist much longer than the course of transcription I'd like to how DNA could remain stable in such a conformation. There are molecular machines inside nuclei that really dont like single stranded DNA, and will chomp it up on sight. If the complementary strand to the i-motif isn't itself moonlighting as some double stranded motif, how is it protected from these dnases. If they are only saying the conformation exists while DNA is undergoing transcription... this isnt exactly on par with a A-,B-,Z-DNA conformations. The primary source is behind a paywal for me (while off campus), but I'll be interested to read more about this later: https://www.nature.com/articles/s41557-018-0046-3 https://www.nature.com/articles/s41557-018-0046-3 (also, how do you confirm the existence of transient structures using fluoro antibodies? 'fret'? 'fish'?)
- alexholehouse 9y agoSo it seems like there are two timescales for what 'transient' means in the paper. 1) There are different levels/numbers of i-motifs identified depending on the cell cycle position (highest at G1/S boundary, although this is only comparing cells synchronized to G1, G1/S and early S so maybe more at different points?), suggesting these structures don't just stably form and then just sit happily around for the entire lifetime of the cell. 2) In vitro these motifs are less stable than (say) G-quadruplexes so presumably there is a suggestion they may be transient over short timescales, but this is not actually examined in the paper. No idea how you'd actually test this without inherently perturbing the equilibrium being examined in vivo. Even if you could avoid fixing the cells antibodies would be out of the question because of the inherent linkage (if you bind the i-motif with a 500 pM Kd [high affinity] you're gonna HUGELY stabilize that conformation).
- subroutine 9y agoI'm curious about this... "What excited us most is that we could see the green spots – the i-motifs – appearing and disappearing over time, so we know that they are forming, dissolving and forming again,” anyone know what technique they used during this observation? It sounds.. not fixed? what matters most in my opinion is whether this is a spontaneous DNA conformation or whether this is a transient conformation DNA assumes while transcription machinery is preparing to read nearby bases. (if the former, kinda interesting; if the latter, much less interesting)
- deleted 9y ago[deleted]
- isthatart 9y agoComputation: “What excited us most is that we could see the green spots – the i-motifs – appearing and disappearing over time, so we know that they are forming, dissolving and forming again,” says Dr Mahdi Zeraati, whose research underpins the study’s findings.
- bitL 9y agoHooray! Finally the inevitable happened! I guess this will turn biology upside down, everybody assumed DNA/RNA were static (with the exception of some primitive viruses). Now how to reverse engineer "machine code"?
- dekhn 9y agothis doesn't turn biology upside down in any way.
- ryanwaggoner 9y agoThis amuses me. When was the last time any major finding turned an entire mature field of study on its head?
- dekhn 9y agoI don't understand. Are you implying this paper is a "major finding"? Many things that happen in biology occur without any real meaning or utility.
- ryanwaggoner 9y agoNo, I'm agreeing with you. I think it rare that any mature field these days is "turned on its head". I doubt most of the examples given by other comments would qualify if you dig into them.
- dekhn 9y agoA good example would be induced pluripotent stem cells nobody thought that that can happen but once it was obvious that you just needed a few transcription factors to move cells from state-to-state. Completely trans formed a field that was already mature
- nukeop 9y agoWill Apple sue the researchers for trademark infringement?
- foxhop 9y agoI wonder if the formation of an i-motif could change the behavior of the "normal" DNA code. Like a flag on a function to slightly change how it works. Could make certain parts of reading normal double helix DNA a no-op, for example by accumulating parts before they can be read. Another idea is maybe this is just a structure for temporary memory for use in a more complex "algorithm". We used to think DNA was just mostly static data but now it seems there is some computation going on. If not computation to change behavior, maybe the i-motif act like a check sum to make sure a complex or essential part of DNA isn't corrupted (by a storage failure or a virus)
- subroutine 9y agoI dont think this motif brings anything spooky/special to the fore. DNA is swarmed by proteins, ribocomplexes, acetyl/methyl histone mods, etc. all of its own making. Whatever special computation one might speculate this motif could perform- that computation or fidelity check or whatever else is probably a known and well-documented function of some DNA-associating complex. While it's fun to speculate how this might 'change the game', in all likelihood, this finding is a very small drop in a very large bucket. But if we are speculating... That a motif forms by a single strand of DNA or RNA is expected (given certain properties or symmetries). What the image in the article depicts and given the quote that this is often seen at start codons, to me, suggests this motif forms whenever transcription machinery has opened the helix creating two single strands. And instead of hanging out as single strands (a very vulnerable state, to DNase degradation, etc) they coil unto themselves. This might also suggest this segment of DNA is relatively easy to unzip, and has built-in degredation protection, making for ideal consensus sequences as start codons.
- epistasis 9y agoSome previous HN discussion of this: https://news.ycombinator.com/item?id=16909328 https://news.ycombinator.com/item?id=16909328
- chiefalchemist 9y agoThe was an article in The Atlantic a couple+ months back - which after 10 mins I still can't find - about some scientist and his alt view / theory on DNA. The gist, if I recall correctly, was (and forgive me if I fall short of capturing the significance of his idea): How DNA functions is far more complicated than how current accepted science pictures it. 1 - Certainly seems like he might be onto something. 2 - If so, could the use of CRISPR be premature, if not dangerous?
- ItsMe000001 9y ago> How DNA functions is far more complicated than how current accepted science pictures it. From what I learned in courses on edX (e.g. MITs Eric Lander's "Introduction to Biology" or RiceX BIOC300.2x "DNA: Biology's Genetic Code"), that is already well known and taught. Scientists are not naive and overconfident in their knowledge, individual examples to the contrary notwithstanding. Guess what - they teach what is actually reliably and verifiably known. It's just a bit too much to expect scientists to work with methods and knowledge they don't even know exist yet, or even to teach them - but that doesn't mean they think they already know it all. Science is full of this exact thing: Layer upon layer of models. Bohr's atom model is very far from what a physics student learns these days. The Newton universe vs. the relativity universe. Chemical bonds in high-school, then in early university chemistry courses, and then what physicists work with who study bonding seems like it comes from entirely different universes, although it all describes the same thing. Same with DNA. The more courses you take the more the knowledge resembles a Mandelbrot set image. Actually, that's a horrible analogy, because in that image when you go deeper you still get similar structures, but when you go deeper in science the same thing starts looking very different. The reason why I still use this analogy is because the part that seems applicable and important is that you can go deeper and deeper and deeper and... (etc.) However, as far as I could tell from just a few courses that complexity already is being taught as far as this is possible (as I mentioned above, it's hard to teach "unknown unknowns", to quote a famous American politician philosopher /s ). What you should keep in mind though is that on each level of knowledge there are a lot - often A LOT - of experiments and applications of that level of knowledge that have been shown to work reliably and well. It's just that new levels of knowledge (and models) open up new possibilities. "Every model is wrong, some models are useful", I only understood what that means when I learned more and more and realized how useless the word "truth" is when attempted to be used in absolute terms. Each model is "true" for the things it successfully and reliably predicts, and for the applications it makes possible. Finding deeper models does not invalidate what you already learned and used successfully. I would suggest seeing science not as the search for "the one final truth". As practised, it is far more practical (yes, same word twice, deliberately). You find something, you demonstrate that it works, you show that it is useful ("you" is many people), you move on. "If you want 'truth' you are in the wrong lecture, philosophy is down the hall" is a sentence I remember to have read having been said a (biology? physics?) professor when he started the first freshman lecture. By concentrating on what you can demonstrate you don't need to have "the final truth" before you are able to do anything useful. You go step by step, and while you don't know if there ever is a final word that does not really matter. That means your statement > How DNA functions is far more complicated than how current accepted science pictures it. actually already is built into science. You can always assume that there is much more that you are not yet aware of.
- klmr 9y agoOriginal paper: https://www.nature.com/articles/s41557-018-0046-3 https://www.nature.com/articles/s41557-018-0046-3 Full text PDF: https://paperpile.com/app/p/ce9c364d-416a-0ede-9233-adf319101f59 https://paperpile.com/app/p/ce9c364d-416a-0ede-9233-adf31910...
- dekhn 9y agoThose of you who are CS people who are trying to stretch this paper into more significant than it is: please go and read all the first-year biology textbooks before speculating.
- laythea 9y agoI am a CS person. If the article is not readily consumable for a CS person why is it on a website called "Hacker News"? Seems like a bad submission if you ask me...
- Jedd 9y ago> I am a CS person. If the article is not readily consumable for a CS person why is it on a website called "Hacker News"? Seems like a bad submission if you ask me... Like many before you, you appear to assume Hacker equates to the C in CS.
- laythea 9y agoLike the many that will, after me, assume Hacker to mean the C in CS. Technically, you are correct, and I agree. But I must point out, that actually, you are wrong - the general use of the word belongs to computers.
- twodave 9y agoWait, they identified it AND managed to get it to tell them its name? Wow!
- deleted 9y ago[deleted]
- lerie82 9y agoThis title is misleading, it's not new.