The big problem I have with the RNA world idea, and its experimental implementation, is that it runs in a soup that doesn't seem plausible.
RNA gets made from pure, energy-rich molecules that themselves are quite complex. This soup of pure monomers isn't something that just arises naturally in the absence of life. Prebiotic chemistry produces a random soup of a wide variety of chemical species, with the abundance of each declining exponentially in its size and complexity.
You see this issue all the time in origin of life claims. For example, that recent result of "all the bases of RNA and DNA were found on this asteroid by the Japanese" tended to slide over the fact that they were there at extremely low levels, mixed with huge numbers of other non-biological organic molecules.
Trying to replicate RNA in a mix of random crap will just give you polymers of crap, if it gave you anything at all.
OoL needs an idea that will work in a soup of junk, not in massively artificial pure soup on a lab bench.
It seems obvious that if replication of elementary particles appears that everything else will be an emerging property given enough time. And if you look at atoms and math there're definite parallels that once atoms can interconnect stronger than everything else (considering the 3d world) and something like Penrose's tiles where you get repeating interconnecting structures that more higher level structures would be possible. And with energy connected to the particles momentum and Heisenberg's uncertainty principle you get fluctuations in the structures that allow for both new structures and enforcing of the construction rules. You also have clear levels between forces that work on different levels that create boundaries to the structures. 3 spacial dimensions give additional directions of interactions between structures. And voila, given conditions, there's a place for emerging properties. Whether it was RNA who knows. It does seem that the search becomes way murkier toward going into the actual mechanism but the ingredients seem to be in place
Is there a reason why the alternative idea of closed autocatalytic sets from Stuart Kauffman doesn't get nearly as much attention or discussion as the RNA origin hypothesis?
Ever since I first learned about it, it seems to me a much more likely origin of life hypothesis, as it doesn't require something to catalyze itself, which causes inevitable problems with mutation causing loss of catalytic efficiency.
Also, it is not incompatible with RNA being one of the early building blocks. It just doesn't require RNA to be where everything started.
“ Holliger’s team looked for catalytic activity in small RNAs (between 20 and 40 nucleotides in length), allowing for small changes in length in each cycle of mutation. They found a 45-nucleotide molecule that they christened QT45 (“quite tiny”) that could seize another RNA strand and copy it. “In principle it can copy any sequence,” Holliger said.”
> There’s scarcely any corner of Earth in which life hasn’t gained a foothold[..]
About that, not that long ago I was entertaining the idea of what environments can be completely devoid of life. I was thinking about examples like a volcano Cauldron, a nuclear reactor or the insides of a particle accelerator.
When I read about self-replicating RNA I always think about the equivalent in the protein world, the prions. One can make many parallelisms with these scary proteins, responsible of the Creutzfeldt-Jakob disease.
Of course, the are too many limitations for evolving into some more complex, but they can self-replicate and they can infect other organisms. If we could give them an oceanic soup of PrPC and enough time, who knows?
Prion "replication" seems rather different from self-replicating RNA.
Isn't the building block that a prion requires to create a copy of itself essentially a chemically almost-identical protein that is just folded differently?
How about an alternative analogy of the prion folding pattern spreading through chemically-similar molecules like a meme through a population of similarly conditioned brains?
The hardest part of the transition from prebiotic chemistry (assembling the building blocks) to an 'RNA World' is doing so in a way that can support RNA copying. As others have shown the chance of finding one replicator is low - so you need supporting RNA copying chemistry at a pretty substantial level to help that happen.
This is where the hard part of the field is currently: finding chemistry that can support accurate RNA copying that is also both sufficiently high yielding and also compatible with these reactions being inside protocells (fatty acids for example). An RNA genome only really has value when it can be selfish and keep any innovations it makes to itself inside a protocell!
I work in Origins Research - if you have questions please ask and ill try to answer with the current opinions of the field!
For a long time, since I learned about how evolution works at the gene level, I’ve been bedazzled by sharks. Here is a configuration of genes which has reached such a sweet spot in the eyes of evolution that it has cruised mostly uncharged (modulo the shrinking due to change in oxygen composition) for hundreds of millions of years. Then I learned about the code of RNA (credit to Deutsch I think in his treatment of evolution in Fabric or maybe it was Beginning, I don’t recall) and my mind was blown! The actual knowledge encoded in the RNA sequence—†not the physical stuff; but the precise coded sequence—required for replication is actually quite ubiquitous across species and unchanged on timescales vastly larger than I had previously fathomed, mountains look like sand castles and sharks are brand new in the eyes of the code of RNA. This is only an analogy; but it felt like how Unix works: RNA is like the tiny kernel which has spread everywhere due to being tiny and good enough to solve the problem and therefore difficult to replace. Anyways, this is only a day dream since I’m not really in the weeds; but I wonder if you can correct any of my misconceptions. Like: RNA is like code for DNA replication, is it sort of like low-level machinery for life? Has the precise RNA code survived a really long time and it’s sort of like an old operating system which just keeps humming in the background? And it is older than sharks right? Any other cool stuff to recommend pursuing for someone like me who really loves evolution; but is just a layperson?
†one note about my em dashes: I am a real person who thinks evolution AND em dashes are cool and for a total aside: it’s such a bummer people think I’m a bot just because I like tinkering w/ f* punctuation marks.
Does the current SOTA believe that it's most likely that life originated on Earth? I know there are some theories that at least one of the critical building blocks was delivered via asteroid or other extra-terrestrial process.
I think the biggest unresolved question isn't whether RNA can replicate itself, but how you get from occasional replication to a self-sustaining system
Most mutations are negative dead-ends, not unlikely DNA now where most pregnancies spontaneously abort due to errors. But life has many, many chances — especially at the molecular scale. So what’s the actual problem?
Similarly, if you have a soup of 10-15 nucleotide sequences, what are the odds actually that they’d link into larger segments?
Let’s suppose that density is a million times lower than blood, so you have one picogram per gram of water. There are 10^24 grams of water on Earth’s surface and 10 base pairs weighs 10^-20 grams, giving us approximately 10^32 segments of that length.
Feel free to play with my numbers, but I’m supposed to believe that with ~10^30 pieces, we can’t have ten of them form the right sequence?
A combinatorial explosion. To have mutations you need to have replication first. If a smallest viable self-replicator is, say, 100 nucleotides long, and there's not many other such replicators of the same length, the improbability of its spontaneous formation (~4^-100) dwarfs any amount of material available on Earth.
The researchers have found QT45 replicator. But it replicates other RNA strands, that is it needs another replicator nearby to replicate itself, which brings the probability down to 4^-90 range.
And it's not clear from the article whether QT45 is a viable replicator. That is whether it is stable enough and replicates other RNA strands correctly enough to sustain exponential growth instead of petering out due to filling its surroundings with broken copies that don't perform replication before decaying itself.
Your numbers are fine - but RNA is fragile; making one copy of something really rare will not be able to do anything as it will not last long enough to meaningfully contribute.
Interestingly we now are thinking about ways to use mutations in other ways, youve spent a lot of energy making these polymers, so it would be a shame to waste that right? We think that they can be used to assemble larger functional pieces as mutations are mostly deterministic meaning you'll get the same kinds of errors - so why not put them to use!
I also don't understand. Adding billions of years to your numbers probably makes it an even better point.
"Life's first molecule." Take your favorite quantum field theory and consider how it draws a line between a molecule and not a molecule. Consider how it draws a line between life or not. That'd be cool. Consider that it doesn't give a shit who did what first.
The big problem I have with the RNA world idea, and its experimental implementation, is that it runs in a soup that doesn't seem plausible.
RNA gets made from pure, energy-rich molecules that themselves are quite complex. This soup of pure monomers isn't something that just arises naturally in the absence of life. Prebiotic chemistry produces a random soup of a wide variety of chemical species, with the abundance of each declining exponentially in its size and complexity.
You see this issue all the time in origin of life claims. For example, that recent result of "all the bases of RNA and DNA were found on this asteroid by the Japanese" tended to slide over the fact that they were there at extremely low levels, mixed with huge numbers of other non-biological organic molecules.
Trying to replicate RNA in a mix of random crap will just give you polymers of crap, if it gave you anything at all.
OoL needs an idea that will work in a soup of junk, not in massively artificial pure soup on a lab bench.
Well we don’t know what is and what’s not possible on a planetary scale (i.e. trillions of interactions daily). At least not yet.
It seems obvious that if replication of elementary particles appears that everything else will be an emerging property given enough time. And if you look at atoms and math there're definite parallels that once atoms can interconnect stronger than everything else (considering the 3d world) and something like Penrose's tiles where you get repeating interconnecting structures that more higher level structures would be possible. And with energy connected to the particles momentum and Heisenberg's uncertainty principle you get fluctuations in the structures that allow for both new structures and enforcing of the construction rules. You also have clear levels between forces that work on different levels that create boundaries to the structures. 3 spacial dimensions give additional directions of interactions between structures. And voila, given conditions, there's a place for emerging properties. Whether it was RNA who knows. It does seem that the search becomes way murkier toward going into the actual mechanism but the ingredients seem to be in place
Lee Cronin's "assembly theory" tries to formalize this idea: https://en.wikipedia.org/wiki/Assembly_theory
Is there a reason why the alternative idea of closed autocatalytic sets from Stuart Kauffman doesn't get nearly as much attention or discussion as the RNA origin hypothesis?
Ever since I first learned about it, it seems to me a much more likely origin of life hypothesis, as it doesn't require something to catalyze itself, which causes inevitable problems with mutation causing loss of catalytic efficiency.
Also, it is not incompatible with RNA being one of the early building blocks. It just doesn't require RNA to be where everything started.
“ Holliger’s team looked for catalytic activity in small RNAs (between 20 and 40 nucleotides in length), allowing for small changes in length in each cycle of mutation. They found a 45-nucleotide molecule that they christened QT45 (“quite tiny”) that could seize another RNA strand and copy it. “In principle it can copy any sequence,” Holliger said.”
You need evolution to have life. Why is mutation a deal-breaker?
> There’s scarcely any corner of Earth in which life hasn’t gained a foothold[..]
About that, not that long ago I was entertaining the idea of what environments can be completely devoid of life. I was thinking about examples like a volcano Cauldron, a nuclear reactor or the insides of a particle accelerator.
If you expand the bounds beyond Earth there are a lot of environments completely devoid of life…
I assume the caldera is hotter than what this little dude can take https://en.wikipedia.org/wiki/Methanopyrus
When I read about self-replicating RNA I always think about the equivalent in the protein world, the prions. One can make many parallelisms with these scary proteins, responsible of the Creutzfeldt-Jakob disease.
Of course, the are too many limitations for evolving into some more complex, but they can self-replicate and they can infect other organisms. If we could give them an oceanic soup of PrPC and enough time, who knows?
Prion "replication" seems rather different from self-replicating RNA.
Isn't the building block that a prion requires to create a copy of itself essentially a chemically almost-identical protein that is just folded differently?
How about an alternative analogy of the prion folding pattern spreading through chemically-similar molecules like a meme through a population of similarly conditioned brains?
The hardest part of the transition from prebiotic chemistry (assembling the building blocks) to an 'RNA World' is doing so in a way that can support RNA copying. As others have shown the chance of finding one replicator is low - so you need supporting RNA copying chemistry at a pretty substantial level to help that happen.
This is where the hard part of the field is currently: finding chemistry that can support accurate RNA copying that is also both sufficiently high yielding and also compatible with these reactions being inside protocells (fatty acids for example). An RNA genome only really has value when it can be selfish and keep any innovations it makes to itself inside a protocell!
I work in Origins Research - if you have questions please ask and ill try to answer with the current opinions of the field!
For a long time, since I learned about how evolution works at the gene level, I’ve been bedazzled by sharks. Here is a configuration of genes which has reached such a sweet spot in the eyes of evolution that it has cruised mostly uncharged (modulo the shrinking due to change in oxygen composition) for hundreds of millions of years. Then I learned about the code of RNA (credit to Deutsch I think in his treatment of evolution in Fabric or maybe it was Beginning, I don’t recall) and my mind was blown! The actual knowledge encoded in the RNA sequence—†not the physical stuff; but the precise coded sequence—required for replication is actually quite ubiquitous across species and unchanged on timescales vastly larger than I had previously fathomed, mountains look like sand castles and sharks are brand new in the eyes of the code of RNA. This is only an analogy; but it felt like how Unix works: RNA is like the tiny kernel which has spread everywhere due to being tiny and good enough to solve the problem and therefore difficult to replace. Anyways, this is only a day dream since I’m not really in the weeds; but I wonder if you can correct any of my misconceptions. Like: RNA is like code for DNA replication, is it sort of like low-level machinery for life? Has the precise RNA code survived a really long time and it’s sort of like an old operating system which just keeps humming in the background? And it is older than sharks right? Any other cool stuff to recommend pursuing for someone like me who really loves evolution; but is just a layperson?
†one note about my em dashes: I am a real person who thinks evolution AND em dashes are cool and for a total aside: it’s such a bummer people think I’m a bot just because I like tinkering w/ f* punctuation marks.
Does the current SOTA believe that it's most likely that life originated on Earth? I know there are some theories that at least one of the critical building blocks was delivered via asteroid or other extra-terrestrial process.
I think the biggest unresolved question isn't whether RNA can replicate itself, but how you get from occasional replication to a self-sustaining system
I don’t understand the objections:
Most mutations are negative dead-ends, not unlikely DNA now where most pregnancies spontaneously abort due to errors. But life has many, many chances — especially at the molecular scale. So what’s the actual problem?
Similarly, if you have a soup of 10-15 nucleotide sequences, what are the odds actually that they’d link into larger segments?
Let’s suppose that density is a million times lower than blood, so you have one picogram per gram of water. There are 10^24 grams of water on Earth’s surface and 10 base pairs weighs 10^-20 grams, giving us approximately 10^32 segments of that length.
Feel free to play with my numbers, but I’m supposed to believe that with ~10^30 pieces, we can’t have ten of them form the right sequence?
> what’s the actual problem?
A combinatorial explosion. To have mutations you need to have replication first. If a smallest viable self-replicator is, say, 100 nucleotides long, and there's not many other such replicators of the same length, the improbability of its spontaneous formation (~4^-100) dwarfs any amount of material available on Earth.
The researchers have found QT45 replicator. But it replicates other RNA strands, that is it needs another replicator nearby to replicate itself, which brings the probability down to 4^-90 range.
And it's not clear from the article whether QT45 is a viable replicator. That is whether it is stable enough and replicates other RNA strands correctly enough to sustain exponential growth instead of petering out due to filling its surroundings with broken copies that don't perform replication before decaying itself.
Your numbers are fine - but RNA is fragile; making one copy of something really rare will not be able to do anything as it will not last long enough to meaningfully contribute.
Interestingly we now are thinking about ways to use mutations in other ways, youve spent a lot of energy making these polymers, so it would be a shame to waste that right? We think that they can be used to assemble larger functional pieces as mutations are mostly deterministic meaning you'll get the same kinds of errors - so why not put them to use!
I also don't understand. Adding billions of years to your numbers probably makes it an even better point.
"Life's first molecule." Take your favorite quantum field theory and consider how it draws a line between a molecule and not a molecule. Consider how it draws a line between life or not. That'd be cool. Consider that it doesn't give a shit who did what first.
"given any word, there's no such thing"