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I have always felt that applying the label "origins of life" research on amino acid/nucleic acid synthesis is extremely misleading. An analogy would be writing

I have always felt that applying the label "origins of life" research on amino acid/nucleic acid synthesis is extremely misleading. An analogy would be writing an article about the natural abundance of silicon on beaches and calling it "how computers are made." We have a decent idea of how the first nucleic acids may have been synthesized, and we have a decent framework for how life evolved from protobiont to prokaryote to eukaryote to multicellular organisms. But there is an absolutely staggering gap between the synthesis of individual nucleotides and the synthesis of the first RNA replicase that we know nearly nothing about.

gliptic 4y ago
If we truly didn't know how computers came about, it's certainly progress to figure out the silicon can come from sand. How is it not origins of life research to attack every step in the process?
- Calavar 4y ago
  It's progress, but the degree of progress is vastly oversold by the media, and sometimes even by academics. Kind of similar to those "amazing new semiconductor" articles that come out every 6 months.
  - soco 4y ago
    Maybe you mean the regular amazing new battery breakthrough?
  - Calavar 4y ago
    Adding to my previous comment: If a student asked "how did life originate?" a response about about nucleic acid synthesis would be a bit disingenuous, because that covers only very, very tiny fraction of the surface area of the problem. The more honest answer would be that there are so many large gaps in our knowledge that we truly don't know. To be clear, I'm not trying to cast skepticism on the whole of biology. There are other questions that we have much better answers to, like the evolutionary pathway from single cellular life to multicellular life. Or the evolutionary link between humans and great apes. But abiogenesis is not one of those questions.
    - marcosdumay 4y ago
      > The more honest answer would be that there are so many large gaps in our knowledge that we truly don't know. Are the gaps really that large? We know that some configurations of nucleotids are enough to create a full metabolism, we know that they arrange at random, and we know how most of them appeared. Except for the few nucleotides that we don't know how they existed, we do know that if you have enough of them on enough places, some kind of life will appear. So looks like the open question here is how those molecules appeared.
      - dathanb82 4y ago
        But RNA / DNA isn't sufficient for life, right? How are proteins synthesized from that string of nucleotides without ribosomes? And nucelotides randomly reshuffling certainly doesn't explain how ribosomes would be created. It's theorized that under the right conditions amino acids will bond to become proteins without needing the mediation of a ribosome. So it's certainly possible that with enough primordial soup you could get proteins. But that doesn't explain how the nucleotide string ends up getting treated as a reusable blueprint for proteins. That seems like a pretty big gap.
        bobthechef 4y ago
        marcosdumay 4y ago
        Ribosomes are mostly RNA, and there is good evidence that they evolved from something that was purely RNA. The aminoacid transport and encoding mechanism is also basically composed of RNA, with some evidence that something like them would work without any of the protein parts. Also, people have created RNA-only self replicating mechanisms that could quite well appear at random, with extremely low odds. Life probably comes from some structure with higher odds that we don't know about, but that's not a huge gap.
        sterlind 4y ago
        I wish I recalled better, but I saw a hypothesis that centered around tRNA rather than the ribosome as the origin of replication. after all, the ribosome simply catalyzes the binding of tRNA to mRNA, and amino acid linkage. iirc the idea centered around the tRNA "code" having a pattern to it - one shaped by its binding affinity to part of the sequence that codes for the tRNA-aminoacyltransferase enzyme itself. I wish I remembered enough to find the reference. edit: ah! think I remembered. the hypothesis was that the codon sequence had some sort of binding affinity to the amino acid it codes for. that there's a relationship between them, suggesting a world where codons attracted amino acids to bind to them without an enzyme linking them. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924937/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924937/
- dieselgate 4y ago
  Just a clarifying question but when you use “attack” do you mean from a “critically minded research focused lens” or a “skeptical” one?
  - trasz 4y ago
- RosanaAnaDana 4y ago
  In the context of building computers and defining computation, silicon can be considered an afterthought. We already had adding machines and the philosophy necessary for digital logic. It may well be the case with the original system that initiated the process we call life. RNA (and by extension DNA) may have been a complete afterthought. I'm always disappointed when I see this research outside of a systems context. Like, sure we can show these things happen, but show me a thermodynamic systems, in place,where this can happen. In you metaphor about sand and beaches, this may be like taking some one to a dune field and saying 'see all this sand. That's where computers come from'.
oneoff786 4y ago
Is that really a staggering gap? The nucleotides jumble together until they randomly hit a config that leads to a pattern that leads to more of that config. We don’t know what that path is exactly but we can be pretty sure it’s the result of random mumbling through a series of random searches in an organic chemistry space. Computers don’t arise randomly (without annoying semantic arguments).
- NateEag 4y ago
  > Computers don’t arise randomly (without annoying semantic arguments). If you believe the human brain's processes are computable, and you believe evolution is a random process, then you believe that computers arise randomly. Is that what you mean by "annoying semantic arguments"?
  - oneoff786 4y ago
    Yes. That is an annoying semantic argument. The intended discussion is pretty clearly a purposefully manufactured device made of silicon and how understanding how that instantiates by watching silicon is not at all like watching how nucleotides arrange into rna. Discussions of what constitutes a computer in this context or whether an nth order effect of a “random” process are just distracting.
    - jdthedisciple 4y ago
      Are you saying you are certain that human DNA was not purposefully manufactured?
      - oneoff786 4y ago
        Human DNA is a lonnnng way down below the timelines and processes we’re talking about buddy.
- tengbretson 4y ago
  > Computers don’t arise randomly You are right. They don't.
photochemsyn 4y ago
It's unlikely that RNA replicases ever existed in the absence of short amino acid polymers. The primordial ribosome might be the concept your looking for - an association between short RNA sequences and short amino acid sequences capable of self-replication via various RNA reactions and amino-catalyzed reactions. This may be the original article discussing this hypothesis: "The ribosome as a missing link in the evolution of life" (2015) Root-Bernstein & Root-Bernstein, J. Theoretical Biology https://sci-hub.se/10.1016/j.jtbi.2014.11.025 https://sci-hub.se/10.1016/j.jtbi.2014.11.025 > "Evolvable entities existing between self-replicating polymers and fully functional cells would presumably have many, though not all, of the functions of a cell, yet be significantly simpler in composition and organization. These entities would be able to self-organize and replicate themselves; store information and replicate that information; translate the information into the components necessary to produce their functional structures; capture metabolic components and energy; and transform these into useful biochemical networks. Norris and his colleagues have called functional forms of organization midway between macromolecules and cells “hyperstructures” (Norris et al., 2007). Such hyperstructures had to be instantiated as evolvable entities, meaning that their components would be subject to variation, replication and natural selection."
pfdietz 4y ago
> We have a decent idea of how the first nucleic acids may have been synthesized, Really? Nucleotides are already too complex to have been produced in any valid OoL experiment at more than vanishingly small concentrations. Experiments that demonstrate some chemical X can be produced, and then lead to another experiment where X is made available in pure form at high concentration (and then rinse and repeat down the synthesis chain), don't tell us anything interesting at all.
TrapLord_Rhodo 4y ago
The whole point of the article was discussing how RNA isn't the orgin of life and we need to push our ideas back further. RNA-Peptide coevolution is the spontaneous immergence of 'replicating' matter. No one molecule in the system has all the requisites for life, but as a whole they do. (I.E.amino acids and nucleobases can transmit information, replicate, move and 'sense' about the world). Pushing this idea of self-replicating orgiins of life back may illuminate the issue. RNA generation doesn't have to be random, it can be selected for like any other evolutionary proceses. Finally, Listen to what you are saying... The rhetoric was much different 10 years ago. We have scientifically narrowed the limit of what we can't explain, and this very small gap in our knowledge is what's left. We are making progress in understandng the origins of life.
- pfdietz 4y ago
  I think you are grossly exaggerating the state of knowledge in the field. No, there's not a "very small gap" left. There's a lot of smoke and speculation and very little actually known.
rojobuffalo 4y ago
Dr. Nick Lane is my favorite author on this subject. My reduced summary of a slide he presented titled "what is life" goes: - free energy powers growth - growth is thermodynamically favorable - heredity is growth, doubling by exact copying - growth combines carbon and energy metabolism - growth is driven by environmental disequilibria That doesn't explain away the mystery of the first RNA replicase, but I really like how it explains growth and doubling as a form a growth. That's copy-pasted from a newsletter draft I'm writing. It'll be posted next week on https://0123.substack.com https://0123.substack.com
- kabdib 4y ago
  If you like Nick Lane's writing, I also recommend David Dreamer's Assembling Life. It gets a good deal more technical (chemical?), and has more depth about possible ways that membranes were "invented". Paul Falkowski's Life's Engines is also quite good.
Thorentis 4y ago
There is also a staggering gap between nucleic acids existing, and just random atoms existing. And then an even more staggering gap between atoms existing, and nothing existing.

gliptic 4y ago

If we truly didn't know how computers came about, it's certainly progress to figure out the silicon can come from sand. How is it not origins of life research to attack every step in the process?

Calavar 4y ago
It's progress, but the degree of progress is vastly oversold by the media, and sometimes even by academics. Kind of similar to those "amazing new semiconductor" articles that come out every 6 months.
- soco 4y ago
  Maybe you mean the regular amazing new battery breakthrough?
- Calavar 4y ago
  Adding to my previous comment: If a student asked "how did life originate?" a response about about nucleic acid synthesis would be a bit disingenuous, because that covers only very, very tiny fraction of the surface area of the problem. The more honest answer would be that there are so many large gaps in our knowledge that we truly don't know. To be clear, I'm not trying to cast skepticism on the whole of biology. There are other questions that we have much better answers to, like the evolutionary pathway from single cellular life to multicellular life. Or the evolutionary link between humans and great apes. But abiogenesis is not one of those questions.
  - marcosdumay 4y ago
    > The more honest answer would be that there are so many large gaps in our knowledge that we truly don't know. Are the gaps really that large? We know that some configurations of nucleotids are enough to create a full metabolism, we know that they arrange at random, and we know how most of them appeared. Except for the few nucleotides that we don't know how they existed, we do know that if you have enough of them on enough places, some kind of life will appear. So looks like the open question here is how those molecules appeared.
    - dathanb82 4y ago
      But RNA / DNA isn't sufficient for life, right? How are proteins synthesized from that string of nucleotides without ribosomes? And nucelotides randomly reshuffling certainly doesn't explain how ribosomes would be created. It's theorized that under the right conditions amino acids will bond to become proteins without needing the mediation of a ribosome. So it's certainly possible that with enough primordial soup you could get proteins. But that doesn't explain how the nucleotide string ends up getting treated as a reusable blueprint for proteins. That seems like a pretty big gap.
      - bobthechef 4y ago
      - marcosdumay 4y ago
        Ribosomes are mostly RNA, and there is good evidence that they evolved from something that was purely RNA. The aminoacid transport and encoding mechanism is also basically composed of RNA, with some evidence that something like them would work without any of the protein parts. Also, people have created RNA-only self replicating mechanisms that could quite well appear at random, with extremely low odds. Life probably comes from some structure with higher odds that we don't know about, but that's not a huge gap.
      - sterlind 4y ago
        I wish I recalled better, but I saw a hypothesis that centered around tRNA rather than the ribosome as the origin of replication. after all, the ribosome simply catalyzes the binding of tRNA to mRNA, and amino acid linkage. iirc the idea centered around the tRNA "code" having a pattern to it - one shaped by its binding affinity to part of the sequence that codes for the tRNA-aminoacyltransferase enzyme itself. I wish I remembered enough to find the reference. edit: ah! think I remembered. the hypothesis was that the codon sequence had some sort of binding affinity to the amino acid it codes for. that there's a relationship between them, suggesting a world where codons attracted amino acids to bind to them without an enzyme linking them. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924937/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924937/
dieselgate 4y ago
Just a clarifying question but when you use “attack” do you mean from a “critically minded research focused lens” or a “skeptical” one?
- trasz 4y ago
RosanaAnaDana 4y ago
In the context of building computers and defining computation, silicon can be considered an afterthought. We already had adding machines and the philosophy necessary for digital logic. It may well be the case with the original system that initiated the process we call life. RNA (and by extension DNA) may have been a complete afterthought. I'm always disappointed when I see this research outside of a systems context. Like, sure we can show these things happen, but show me a thermodynamic systems, in place,where this can happen. In you metaphor about sand and beaches, this may be like taking some one to a dune field and saying 'see all this sand. That's where computers come from'.

oneoff786 4y ago

Is that really a staggering gap? The nucleotides jumble together until they randomly hit a config that leads to a pattern that leads to more of that config. We don’t know what that path is exactly but we can be pretty sure it’s the result of random mumbling through a series of random searches in an organic chemistry space. Computers don’t arise randomly (without annoying semantic arguments).

NateEag 4y ago
> Computers don’t arise randomly (without annoying semantic arguments). If you believe the human brain's processes are computable, and you believe evolution is a random process, then you believe that computers arise randomly. Is that what you mean by "annoying semantic arguments"?
- oneoff786 4y ago
  Yes. That is an annoying semantic argument. The intended discussion is pretty clearly a purposefully manufactured device made of silicon and how understanding how that instantiates by watching silicon is not at all like watching how nucleotides arrange into rna. Discussions of what constitutes a computer in this context or whether an nth order effect of a “random” process are just distracting.
  - jdthedisciple 4y ago
    Are you saying you are certain that human DNA was not purposefully manufactured?
    - oneoff786 4y ago
      Human DNA is a lonnnng way down below the timelines and processes we’re talking about buddy.
tengbretson 4y ago
> Computers don’t arise randomly You are right. They don't.

photochemsyn 4y ago

It's unlikely that RNA replicases ever existed in the absence of short amino acid polymers. The primordial ribosome might be the concept your looking for - an association between short RNA sequences and short amino acid sequences capable of self-replication via various RNA reactions and amino-catalyzed reactions. This may be the original article discussing this hypothesis: "The ribosome as a missing link in the evolution of life" (2015) Root-Bernstein & Root-Bernstein, J. Theoretical Biology https://sci-hub.se/10.1016/j.jtbi.2014.11.025 https://sci-hub.se/10.1016/j.jtbi.2014.11.025 > "Evolvable entities existing between self-replicating polymers and fully functional cells would presumably have many, though not all, of the functions of a cell, yet be significantly simpler in composition and organization. These entities would be able to self-organize and replicate themselves; store information and replicate that information; translate the information into the components necessary to produce their functional structures; capture metabolic components and energy; and transform these into useful biochemical networks. Norris and his colleagues have called functional forms of organization midway between macromolecules and cells “hyperstructures” (Norris et al., 2007). Such hyperstructures had to be instantiated as evolvable entities, meaning that their components would be subject to variation, replication and natural selection."

pfdietz 4y ago

> We have a decent idea of how the first nucleic acids may have been synthesized, Really? Nucleotides are already too complex to have been produced in any valid OoL experiment at more than vanishingly small concentrations. Experiments that demonstrate some chemical X can be produced, and then lead to another experiment where X is made available in pure form at high concentration (and then rinse and repeat down the synthesis chain), don't tell us anything interesting at all.

TrapLord_Rhodo 4y ago

The whole point of the article was discussing how RNA isn't the orgin of life and we need to push our ideas back further. RNA-Peptide coevolution is the spontaneous immergence of 'replicating' matter. No one molecule in the system has all the requisites for life, but as a whole they do. (I.E.amino acids and nucleobases can transmit information, replicate, move and 'sense' about the world). Pushing this idea of self-replicating orgiins of life back may illuminate the issue. RNA generation doesn't have to be random, it can be selected for like any other evolutionary proceses. Finally, Listen to what you are saying... The rhetoric was much different 10 years ago. We have scientifically narrowed the limit of what we can't explain, and this very small gap in our knowledge is what's left. We are making progress in understandng the origins of life.

pfdietz 4y ago
I think you are grossly exaggerating the state of knowledge in the field. No, there's not a "very small gap" left. There's a lot of smoke and speculation and very little actually known.

rojobuffalo 4y ago

Dr. Nick Lane is my favorite author on this subject. My reduced summary of a slide he presented titled "what is life" goes: - free energy powers growth - growth is thermodynamically favorable - heredity is growth, doubling by exact copying - growth combines carbon and energy metabolism - growth is driven by environmental disequilibria That doesn't explain away the mystery of the first RNA replicase, but I really like how it explains growth and doubling as a form a growth. That's copy-pasted from a newsletter draft I'm writing. It'll be posted next week on https://0123.substack.com https://0123.substack.com

kabdib 4y ago
If you like Nick Lane's writing, I also recommend David Dreamer's Assembling Life. It gets a good deal more technical (chemical?), and has more depth about possible ways that membranes were "invented". Paul Falkowski's Life's Engines is also quite good.

Thorentis 4y ago

There is also a staggering gap between nucleic acids existing, and just random atoms existing. And then an even more staggering gap between atoms existing, and nothing existing.