4 ms·

No, it's not as simple as that. The probability of self-replicating RNA arising by random assembly of bases is very low. There was a good Nature article [1] pub

No, it's not as simple as that. The probability of self-replicating RNA arising by random assembly of bases is very low. There was a good Nature article [1] published a couple years back that digs through some of the numerical issues. (And a good, more layperson oriented summary as well [2].) The gist is that a self-replicating RNA sequence would have to be at least 40 nucleotides (and possibly even as long as 100), but the probability of randomly synthesizing a 40-nucleotide long sequence that happens to be self-replicating anywhere in the visible universe over the span of 13 billion years is effectively zero. To be fair, the probability gets closer to one if you expand your view to include the entire universe and assume that it is many, many orders of magnitude larger than the visible universe. But my take away, at least, is that we are not dealing with a situation where random assembly of RNA is so likely to generate self-replicating sequences that abiogenesis was effectively an inevitability. That was the narrative I was sold in grade school and undergrad, but it appears to be wrong. There are a good number of free parameters in the journal article that I linked: The fraction of RNA sequences that are self-replicating, the fraction of planets that are habitable for life, the average decay rate of RNA on a habitable planet, etc. You take can take issue with the empirical estimates for those parameters, but that points to missing pieces in the framework: Was there a chemical process on early earth that stabilized RNA oligomers that no longer exists? Are self-replicating RNA sequences more common than we believe? If so, why haven't we encountered more of them in nature? And so on. In my opinion, these are the truly interesting questions, not whether nucleotides and amino acids can form spontaneously. [1] https://www.nature.com/articles/s41598-020-58060-0 https://www.nature.com/articles/s41598-020-58060-0 [2] https://mathscholar.org/2020/05/the-origin-of-life-in-an-inflationary-universe/ https://mathscholar.org/2020/05/the-origin-of-life-in-an-inf...

trasz 4y ago
>The probability of self-replicating RNA arising by random assembly of bases is very low. But it parallelizes extremely well - throughout the entire universe for billions of years.
- JJMcJ 4y ago
  Or here on Earth over say 100 million years with trillions of little globs of organic chemicals, likely with even simpler replication mechanisms that are not understood currently.
  - trasz 4y ago
    Well, sure, but it wasn’t just Earth - literally everything in observable universe was involved in some complicated processes; it’s just that we came from a particular “branch” of this process and thus assume we’re the most extra special thing in the entire universe. And then of course there’s https://en.m.wikipedia.org/wiki/Panpsychism https://en.m.wikipedia.org/wiki/Panpsychism.
oneoff786 4y ago
Undiscovered mechanisms of self replicating RNA arising by chance seems very likely though. That’s my point. I agree there’s a lot of good questions to be answered. I think it is likely that we will answer them by staring at nucleotide soup.
skupig 4y ago
>the probability [...] is effectively zero Is that meaningful? No matter how unlikely our existence is, here we are.
pfdietz 4y ago
Back up from that... how are the nucleotides formed? And don't they need energetic polyphosphate groups on them to drive the polymerization? And how does this work in an impure solution with all sorts of variant nucleotides and other cruft?
JJMcJ 4y ago
To my thinking, that means that self replicating systems arose in an even simpler chemical environment and even RNA was a later development.
adgjlsfhk1 4y ago
What this is missing is that it assumes way too little structure. You don't have to generate a self replicating set of RNA. Many RNA strands (maybe most?) will do something, so all you need is to generate a strand of RNA that will eventually produce a self replicating set of RNA which is likely much easier.
lisper 4y ago
> Are self-replicating RNA sequences more common than we believe? Almost certainly yes. > If so, why haven't we encountered more of them in nature? Because they can't compete with modern life. Nearly all of the biomass on earth is in use. A primitive replicator, even if it arose today, would have to compete for resources against all the existing life on earth. It wouldn't stand a chance. This is the reason there is only one universal common ancestor. It's not necessarily that abiogenesis only happened once, it's that only the descendants of one common ancestor survive today. All traces of all other abiogenesis events have been obliterated. You have to compute the abiogenesis odds for an environment that, by definition, does not yet include life. Here is a rough back-of-the-envelope approximation: the biomass of earth is about 2^52kg. Avogadro's number is 2^76. So there is the potential for the early earth to have 2^120 nucleotide bases and amino acid molecules floating around. If the complexity of a simple replicator is around O(100) bits then the odds of finding one by chance when you are rolling that many dice in parallel approaches 1 in just a few million years. After that, evolution takes over.
- Calavar 4y ago
  First, the majority of the biomass of the earth is water, not organic molecules, and big fraction of what's left is lipids and carbohydrates, not nucleic or amino acids. So a simple multiplication of biomass by Avogadro's number is likely off by at least an order of magnitude. Second, yes, today's world has an enormous amount of amino acids and nucleic acids, but that is after billions of years of enzyme-catalyzed synthesis inside trillions of living cells. The prevalence of amino acids/nucleic acids prior to abiogenesis would have been orders of magnitude lower in a world where those enzyme pathways didn't exist yet and biologic molecules with catalytic activity were still in the process of being bootstrapped. Third, does your back of the envelope calculation account for the very short half life of RNA? That is really the biggest issue. If RNA didn't decay, then forget about hundred base sequences; the primordial earth might have been filled with million base sequences.
  - lisper 4y ago
    > the majority of the biomass of the earth is water The figure I cited is the carbon biomass. https://www.visualcapitalist.com/all-the-biomass-of-earth-in-one-graphic/ https://www.visualcapitalist.com/all-the-biomass-of-earth-in... > that is after billions of years of enzyme-catalyzed synthesis inside trillions of living cells Doesn't matter. What matters is the size of the search space that could be explored by the chemistry, and if even a single replicator exists in that search space. The extent to which that first replicator resembles present-day life is irrelevant. The only reason to refer to that at all is to get some idea of what the information content of a minimal replicator is. > Third, does your back of the envelope calculation account for the very short half life of RNA? Again, it doesn't matter. As long as the half-life of the replicator is more than the time it takes it to produce >2 offspring, that's enough to get the ball rolling.

trasz 4y ago

>The probability of self-replicating RNA arising by random assembly of bases is very low. But it parallelizes extremely well - throughout the entire universe for billions of years.

JJMcJ 4y ago
Or here on Earth over say 100 million years with trillions of little globs of organic chemicals, likely with even simpler replication mechanisms that are not understood currently.
- trasz 4y ago
  Well, sure, but it wasn’t just Earth - literally everything in observable universe was involved in some complicated processes; it’s just that we came from a particular “branch” of this process and thus assume we’re the most extra special thing in the entire universe. And then of course there’s https://en.m.wikipedia.org/wiki/Panpsychism https://en.m.wikipedia.org/wiki/Panpsychism.

oneoff786 4y ago

Undiscovered mechanisms of self replicating RNA arising by chance seems very likely though. That’s my point. I agree there’s a lot of good questions to be answered. I think it is likely that we will answer them by staring at nucleotide soup.

skupig 4y ago

>the probability [...] is effectively zero Is that meaningful? No matter how unlikely our existence is, here we are.

pfdietz 4y ago

Back up from that... how are the nucleotides formed? And don't they need energetic polyphosphate groups on them to drive the polymerization? And how does this work in an impure solution with all sorts of variant nucleotides and other cruft?

JJMcJ 4y ago

To my thinking, that means that self replicating systems arose in an even simpler chemical environment and even RNA was a later development.

adgjlsfhk1 4y ago

What this is missing is that it assumes way too little structure. You don't have to generate a self replicating set of RNA. Many RNA strands (maybe most?) will do something, so all you need is to generate a strand of RNA that will eventually produce a self replicating set of RNA which is likely much easier.

lisper 4y ago

> Are self-replicating RNA sequences more common than we believe? Almost certainly yes. > If so, why haven't we encountered more of them in nature? Because they can't compete with modern life. Nearly all of the biomass on earth is in use. A primitive replicator, even if it arose today, would have to compete for resources against all the existing life on earth. It wouldn't stand a chance. This is the reason there is only one universal common ancestor. It's not necessarily that abiogenesis only happened once, it's that only the descendants of one common ancestor survive today. All traces of all other abiogenesis events have been obliterated. You have to compute the abiogenesis odds for an environment that, by definition, does not yet include life. Here is a rough back-of-the-envelope approximation: the biomass of earth is about 2^52kg. Avogadro's number is 2^76. So there is the potential for the early earth to have 2^120 nucleotide bases and amino acid molecules floating around. If the complexity of a simple replicator is around O(100) bits then the odds of finding one by chance when you are rolling that many dice in parallel approaches 1 in just a few million years. After that, evolution takes over.

Calavar 4y ago
First, the majority of the biomass of the earth is water, not organic molecules, and big fraction of what's left is lipids and carbohydrates, not nucleic or amino acids. So a simple multiplication of biomass by Avogadro's number is likely off by at least an order of magnitude. Second, yes, today's world has an enormous amount of amino acids and nucleic acids, but that is after billions of years of enzyme-catalyzed synthesis inside trillions of living cells. The prevalence of amino acids/nucleic acids prior to abiogenesis would have been orders of magnitude lower in a world where those enzyme pathways didn't exist yet and biologic molecules with catalytic activity were still in the process of being bootstrapped. Third, does your back of the envelope calculation account for the very short half life of RNA? That is really the biggest issue. If RNA didn't decay, then forget about hundred base sequences; the primordial earth might have been filled with million base sequences.
- lisper 4y ago
  > the majority of the biomass of the earth is water The figure I cited is the carbon biomass. https://www.visualcapitalist.com/all-the-biomass-of-earth-in-one-graphic/ https://www.visualcapitalist.com/all-the-biomass-of-earth-in... > that is after billions of years of enzyme-catalyzed synthesis inside trillions of living cells Doesn't matter. What matters is the size of the search space that could be explored by the chemistry, and if even a single replicator exists in that search space. The extent to which that first replicator resembles present-day life is irrelevant. The only reason to refer to that at all is to get some idea of what the information content of a minimal replicator is. > Third, does your back of the envelope calculation account for the very short half life of RNA? Again, it doesn't matter. As long as the half-life of the replicator is more than the time it takes it to produce >2 offspring, that's enough to get the ball rolling.