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I think the whole RNA thing is a bit over hyped. People like RNA because it looks somewhat like computer code, and our technology is just smitten with computers

I think the whole RNA thing is a bit over hyped. People like RNA because it looks somewhat like computer code, and our technology is just smitten with computers, these recent decades. And right along with that, it makes for such a painfully obvious way to implement inheritance and natural selection, a way to make genes. But I think our focus is too narrow, we should think bigger than just obvious solutions. Now, it's great if the early oceans were awash with RNA, but does RNA exploit energy gradients on its own? The idea of all this random RNA just sloshing around, using nothing more than entropy, behaving as genes and inventing all the rest of it, just seems a little cart-before-the-horse. What about metabolism-first? Is fire alive? It has many properties of life but, critically, lacks self regulation and heritability. Burns everything and goes out. Imagine though, a system of enzymes that can assimilate various specific kinds of molecules, and sustain production of those enzymes. Imagine this contained, compartmentalized in some way. Dynamically not much more complicated than simple fire, but crucially, the enzymes can be said to be inherited. These are not 'genes' as such, these are the actual machinery. It should be possible for natural selection to act on 'life' no more complicated than that. And that kind of system could then take find uses for RNA. (And yes, the enzymes I refer to could be realized as RNA, but acting as the enzymes directly, not merely describing them, and this would confer some major benefits)

tetris11 4y ago
It's not quite a random soup though, RNA folding usually tries to minimize the energy exerted during the folding and binding process, no? Isn't this similar with fire, and enzymes, and other unconscious actors that appear to exhibit complex behavoirs but are just minimising some energy gradient?
- greenbit 4y ago
  I'm just painting broad strokes, trying to avoid the TL;DR threshold. But re energy gradients, I'm talking about the difference between being able to tap into potential energy in the environment, vs just seeking some kind of equilibrium. Sure, a freshly crafted sequence of amino acids will find a shape to minimize the internal energy, and so you can say there's a gradient there, but that's different from taking in H2S and CO2 (or what have you) from the environment and reacting them to liberate non-thermal energy that can be used to get things done.
  - Ultimatt 4y ago
    greenbit so in your mind what is a viroid? We have examples that are extant of RNA doing this. Sure its exploiting an established RNA system, but the point still stands as there's absolutely no reason you couldn't have viroids dealing with other catalytic networks making RNA. That's sort of the point, at some point everything was wandering viroids among autocatalytic networks with varying survival rates. That gets you selective pressure. Thats the transition you're talking about, from autocatalytic localised chemistry into RNA. The initial fitness benefit of RNA is that for one class of molecule you can have a lot of complex catalytic chemistry AND they have the ability through base pairing to catalyse their own exact replication.
greenbit 4y ago
Some afterthoughts: In seeking abiogenesis what we're really looking for is the first replicators. Certainly RNA strands can self replicate, but how is a particular sequence alive? About as alive as a virus, perhaps. Ok, posit a whole world of naked RNA, with multitudes of different sequences. Has life arrived on such a world? I'd say the interesting event would still be downstream from there, when by chance some of those different sequences happened to cooperate to mutual advantage. But that's like viruses inventing the cell. Whereas, if you allow for the spontaneous collaboration of mere enzymes to create self sustaining metabolism, you can get a system that should exhibit natural selection, even without genes. I guess what I'm railing on about is this notion that we have one class of molecules that do the work, and another that merely describes other molecules. We create categories and labels for what we see, and then get stuck within those constructs. Truth is often more subtle.
- Ultimatt 4y ago
  RNA does all of those functions, thats why people think it was prevalent before DNA. There are very few DNA enzymes compared to RNA. RNA provides structure in complex with other molecules which is indirectly catalytic to their activity, as well as being catalytic directly from its own folded structure, then you also have coded information representing its own structure but later those of proteins with the establishment of the genetic code. But you have to remember ribosomes have to exist for the genetic code to mean anything, or at least whatever ribosomes looked like at the start, which is very likely just RNA and a couple of peptides.
  - ianai 4y ago
    Saw a video on YT that I think was saying what you just described might eventually build up a living cell. That would be pretty huge.
- lupire 4y ago
  Life is not a binary. Life is a gradient of complexity.
- robbiep 4y ago
ramraj07 4y ago
It’s often hard to tell between a genius who’s so far out away from others that what they say doesn’t make any sense or someone who has no clue what’s actually known about something. I’ll give that benefit of doubt to you but suffice to say I have no idea what you’re talking about. The rna hypothesis is not overhyped. The fact of the matter is rna looks like a likely candidate that can form in the conditions of early earth, and it’s a perfect candidate for a single molecule that can become self replicating. We don’t know the math of the probability that this thing happened and how big an experiment volume we had in terms of environment size and time span, so hard to tell if this happened this way or not. Suffice to say I see no other plausible hypothesis proposed that is as believable as the RNA world. At least something I can understand anyway. FWIW I do believe in the RNA world hypothesis only I don’t think it happened in earth, but some other planet at some point in past. I just think that space is filled with floating frozen microbial spores that can instantly (geologically speaking) inoculate any planet with the right conditions.
- uplifter 4y ago
  Not the GP but maybe I can help elucidate the position they're representing. The GP advocates for what is known as the "metabolism-first" hypothesis in origins of life theory. The motivation of this theory that some chemists and biologists find it implausible that a self-catalyzing RNA based biological machinery would have formed spontaneously from a collection of basic precursor chemicals, even given very long spans of time and large volumes of precursors. They believe this because nucleic acids are very complex structures and themselves require very complex biologic machinery to assemble, and their understanding of the likelihood of chemical reactions suggests its unreasonable to expect them to form in geological time spans. They posit that instead its more likely that nucleic acid based systems were themselves preceded by system(s) composed of sets of simpler chemicals (ones which are likely to form spontaneously) which together catalyze each other's formation (a so-called "auto-catalytic set"), and that this era of simple metabolisms eventually produced a nucleic acid based system which completely overtook and replaced/assimilated the more primitive auto-catalytic set world. Here's a primer on the metabolism-first hypothesis: https://www.statedclearly.com/videos/what-is-the-metabolism-first-hypothesis-for-the-origin-of-life/ https://www.statedclearly.com/videos/what-is-the-metabolism-...
uplifter 4y ago
You seem to already know this, but "Metabolism First" is the name used for the theory in biology that you just described[0] The idea is that some self-catalyzing cycle(s) of reactions among chemicals structurally much simpler than nucleotides or even protein enzymes preceded the era of nucleic acid based biology, until being completely (or replaced) by said RNA/DNA based systems. [0] Metabolism First primer: https://www.statedclearly.com/videos/what-is-the-metabolism-first-hypothesis-for-the-origin-of-life/ https://www.statedclearly.com/videos/what-is-the-metabolism-...
Ultimatt 4y ago
The RNA thing is more about what was the first storage of genetic heritable information, I don't know anyone in academia who imagines some kind of RNA world where auto catalytic networks weren't established first or alongside... So yes? You're creating a weird straw man argument for yourself. No one doesn't agree with you. That doesn't take away from the idea of stored information being in RNA before say DNA as it is today. Some of the more fun theories I've seen also focus around the ribosome as the original primary replicator rather than cells. With cells being the evolutionary consequence of ribosomes improving their efficiency.
- greenbit 4y ago
  Maybe it's the sources I look at, which unfortunately tend to be journalistic rather than scientific. So I encounter something like 10x as many items about RNA/DNA for every one about abiogenesis that focuses on something else.
zmgsabst 4y ago
> (And yes, the enzymes I refer to could be realized as RNA, but acting as the enzymes directly, not merely describing them, and this would confer some major benefits) Isn’t the standard model that chemical complexes of increasing sophistication formed around volcanic vents until the molecules involved looked like viroids or other ribozymes? Then there’s an evolutionary fork, where the RNA moves towards DNA for storage and proteins for work, but the relationship remains mediated by RNA, eg in mitochondria.
flobosg 4y ago
> And yes, the enzymes I refer to could be realized as RNA, but acting as the enzymes directly, not merely describing them RNA can act as an enzyme (https://en.wikipedia.org/wiki/Ribozyme https://en.wikipedia.org/wiki/Ribozyme). This fact is one of the arguments in favor of the RNA world hypothesis.
topher515 4y ago
If you haven't read "The Vital Question" by Nick Lane yet, then you really should. One of the book's suggestions is that an energy-first analysis of life and the origins of life, can be incredibly explanatory—particularly since Science (and Pop-Science) has been so focused on genetics for so long. In terms of the origins of life, the idea is essentially that rather than try to imagine how RNA could "just appear", we should look for places where there were natural, persistent, energy fluxes (the "fires" as you say), and try to understand how these energy fluxes began to resemble cells. i.e., were constrained into cell-sizes and began replicating. Incidentally, the theory that Nick Lane puts forward of which particular energy fluxes gave rise to life is sea-floor alkaline hydrothermal vents[1]—which is also discussed in the book. [1] https://nick-lane.net/publications/origin-life-alkaline-hydrothermal-vents-2/ https://nick-lane.net/publications/origin-life-alkaline-hydr...
- adampwells 4y ago
  There is a podcast interview [1] with Nick Lane by Sean Carrol that goes into more detail along these lines - a very compelling argument! [1]https://www.preposterousuniverse.com/podcast/2022/05/23/198-nick-lane-on-powering-biology/ https://www.preposterousuniverse.com/podcast/2022/05/23/198-...

tetris11 4y ago

It's not quite a random soup though, RNA folding usually tries to minimize the energy exerted during the folding and binding process, no? Isn't this similar with fire, and enzymes, and other unconscious actors that appear to exhibit complex behavoirs but are just minimising some energy gradient?

greenbit 4y ago
I'm just painting broad strokes, trying to avoid the TL;DR threshold. But re energy gradients, I'm talking about the difference between being able to tap into potential energy in the environment, vs just seeking some kind of equilibrium. Sure, a freshly crafted sequence of amino acids will find a shape to minimize the internal energy, and so you can say there's a gradient there, but that's different from taking in H2S and CO2 (or what have you) from the environment and reacting them to liberate non-thermal energy that can be used to get things done.
- Ultimatt 4y ago
  greenbit so in your mind what is a viroid? We have examples that are extant of RNA doing this. Sure its exploiting an established RNA system, but the point still stands as there's absolutely no reason you couldn't have viroids dealing with other catalytic networks making RNA. That's sort of the point, at some point everything was wandering viroids among autocatalytic networks with varying survival rates. That gets you selective pressure. Thats the transition you're talking about, from autocatalytic localised chemistry into RNA. The initial fitness benefit of RNA is that for one class of molecule you can have a lot of complex catalytic chemistry AND they have the ability through base pairing to catalyse their own exact replication.

greenbit 4y ago

Some afterthoughts: In seeking abiogenesis what we're really looking for is the first replicators. Certainly RNA strands can self replicate, but how is a particular sequence alive? About as alive as a virus, perhaps. Ok, posit a whole world of naked RNA, with multitudes of different sequences. Has life arrived on such a world? I'd say the interesting event would still be downstream from there, when by chance some of those different sequences happened to cooperate to mutual advantage. But that's like viruses inventing the cell. Whereas, if you allow for the spontaneous collaboration of mere enzymes to create self sustaining metabolism, you can get a system that should exhibit natural selection, even without genes. I guess what I'm railing on about is this notion that we have one class of molecules that do the work, and another that merely describes other molecules. We create categories and labels for what we see, and then get stuck within those constructs. Truth is often more subtle.

Ultimatt 4y ago
RNA does all of those functions, thats why people think it was prevalent before DNA. There are very few DNA enzymes compared to RNA. RNA provides structure in complex with other molecules which is indirectly catalytic to their activity, as well as being catalytic directly from its own folded structure, then you also have coded information representing its own structure but later those of proteins with the establishment of the genetic code. But you have to remember ribosomes have to exist for the genetic code to mean anything, or at least whatever ribosomes looked like at the start, which is very likely just RNA and a couple of peptides.
- ianai 4y ago
  Saw a video on YT that I think was saying what you just described might eventually build up a living cell. That would be pretty huge.
lupire 4y ago
Life is not a binary. Life is a gradient of complexity.
robbiep 4y ago

ramraj07 4y ago

It’s often hard to tell between a genius who’s so far out away from others that what they say doesn’t make any sense or someone who has no clue what’s actually known about something. I’ll give that benefit of doubt to you but suffice to say I have no idea what you’re talking about. The rna hypothesis is not overhyped. The fact of the matter is rna looks like a likely candidate that can form in the conditions of early earth, and it’s a perfect candidate for a single molecule that can become self replicating. We don’t know the math of the probability that this thing happened and how big an experiment volume we had in terms of environment size and time span, so hard to tell if this happened this way or not. Suffice to say I see no other plausible hypothesis proposed that is as believable as the RNA world. At least something I can understand anyway. FWIW I do believe in the RNA world hypothesis only I don’t think it happened in earth, but some other planet at some point in past. I just think that space is filled with floating frozen microbial spores that can instantly (geologically speaking) inoculate any planet with the right conditions.

uplifter 4y ago
Not the GP but maybe I can help elucidate the position they're representing. The GP advocates for what is known as the "metabolism-first" hypothesis in origins of life theory. The motivation of this theory that some chemists and biologists find it implausible that a self-catalyzing RNA based biological machinery would have formed spontaneously from a collection of basic precursor chemicals, even given very long spans of time and large volumes of precursors. They believe this because nucleic acids are very complex structures and themselves require very complex biologic machinery to assemble, and their understanding of the likelihood of chemical reactions suggests its unreasonable to expect them to form in geological time spans. They posit that instead its more likely that nucleic acid based systems were themselves preceded by system(s) composed of sets of simpler chemicals (ones which are likely to form spontaneously) which together catalyze each other's formation (a so-called "auto-catalytic set"), and that this era of simple metabolisms eventually produced a nucleic acid based system which completely overtook and replaced/assimilated the more primitive auto-catalytic set world. Here's a primer on the metabolism-first hypothesis: https://www.statedclearly.com/videos/what-is-the-metabolism-first-hypothesis-for-the-origin-of-life/ https://www.statedclearly.com/videos/what-is-the-metabolism-...

uplifter 4y ago

You seem to already know this, but "Metabolism First" is the name used for the theory in biology that you just described[0] The idea is that some self-catalyzing cycle(s) of reactions among chemicals structurally much simpler than nucleotides or even protein enzymes preceded the era of nucleic acid based biology, until being completely (or replaced) by said RNA/DNA based systems. [0] Metabolism First primer: https://www.statedclearly.com/videos/what-is-the-metabolism-first-hypothesis-for-the-origin-of-life/ https://www.statedclearly.com/videos/what-is-the-metabolism-...

Ultimatt 4y ago

The RNA thing is more about what was the first storage of genetic heritable information, I don't know anyone in academia who imagines some kind of RNA world where auto catalytic networks weren't established first or alongside... So yes? You're creating a weird straw man argument for yourself. No one doesn't agree with you. That doesn't take away from the idea of stored information being in RNA before say DNA as it is today. Some of the more fun theories I've seen also focus around the ribosome as the original primary replicator rather than cells. With cells being the evolutionary consequence of ribosomes improving their efficiency.

greenbit 4y ago
Maybe it's the sources I look at, which unfortunately tend to be journalistic rather than scientific. So I encounter something like 10x as many items about RNA/DNA for every one about abiogenesis that focuses on something else.

zmgsabst 4y ago

> (And yes, the enzymes I refer to could be realized as RNA, but acting as the enzymes directly, not merely describing them, and this would confer some major benefits) Isn’t the standard model that chemical complexes of increasing sophistication formed around volcanic vents until the molecules involved looked like viroids or other ribozymes? Then there’s an evolutionary fork, where the RNA moves towards DNA for storage and proteins for work, but the relationship remains mediated by RNA, eg in mitochondria.

flobosg 4y ago

> And yes, the enzymes I refer to could be realized as RNA, but acting as the enzymes directly, not merely describing them RNA can act as an enzyme (https://en.wikipedia.org/wiki/Ribozyme https://en.wikipedia.org/wiki/Ribozyme). This fact is one of the arguments in favor of the RNA world hypothesis.

topher515 4y ago

If you haven't read "The Vital Question" by Nick Lane yet, then you really should. One of the book's suggestions is that an energy-first analysis of life and the origins of life, can be incredibly explanatory—particularly since Science (and Pop-Science) has been so focused on genetics for so long. In terms of the origins of life, the idea is essentially that rather than try to imagine how RNA could "just appear", we should look for places where there were natural, persistent, energy fluxes (the "fires" as you say), and try to understand how these energy fluxes began to resemble cells. i.e., were constrained into cell-sizes and began replicating. Incidentally, the theory that Nick Lane puts forward of which particular energy fluxes gave rise to life is sea-floor alkaline hydrothermal vents[1]—which is also discussed in the book. [1] https://nick-lane.net/publications/origin-life-alkaline-hydrothermal-vents-2/ https://nick-lane.net/publications/origin-life-alkaline-hydr...

adampwells 4y ago
There is a podcast interview [1] with Nick Lane by Sean Carrol that goes into more detail along these lines - a very compelling argument! [1]https://www.preposterousuniverse.com/podcast/2022/05/23/198-nick-lane-on-powering-biology/ https://www.preposterousuniverse.com/podcast/2022/05/23/198-...