11 ms·

Scientists who have done the math disagree. It's a major current issue. It's extremely difficult to produce useful proteins from random DNA chains. As in, if I

Scientists who have done the math disagree. It's a major current issue. It's extremely difficult to produce useful proteins from random DNA chains. As in, if I took all of the atoms in our galaxy, paired each with random DNA, and allowed you to pick just one (blindfolded), only one of those DNA strands would contain the DNA necessary to produce a valid/useful protein. Literally every other atom has garbage DNA/proteins. The human body contains between 80,000 and 400,000 proteins. DNA looks far more like "information" than it does like random bits written to disk. It's analogous to trying to find an x86 program of at least 160 instructions that computes a valid mathematical function by randomly splatting 1s and 0s to disk and then "running" the "code". Eh, maybe it'll eventually happen, but you can see how hard it actually is in practice. Heat-death-of-the-Universe hard. Give a long enough timeframe, even unlikely things will happen. However, the Universe isn't very old—which is why it's a major current issue.

sveme 6y ago
Well, that's why an RNA first world is most likely. RNA can act catalytically as RNAzymes.
chmod775 6y ago
This assumes a perfect random distribution though. What if amino acids and proteins are in fact likely to arise naturally and in favorable circumstances? There was an article recently (~1-2 months) on HN about a supercomputer/AI discovering new chemical pathways for part of this process, but I can't seem to find it anymore. I think it was about forming amino acids. I'm no expert on this subject (the opposite really, I've slept through chemistry), but my experience with large-scale simulations has been that a surprising number of them converge to the same final result given the same starting parameters even if most processes within them are perfectly random. The bigger the simulation, the more likely they are to give you stable results. And the universe is pretty damn huge. So I like to believe the creation of the foundations of life is in fact more-or-less inevitable in our universe, in turn increasing the chance of useful proteins etc. forming.
- erichocean 6y ago
  > And the universe is pretty damn huge. And that kind of hand-wavey statement seems to convince most people. Universe is hella-old, and really big. Ergo, incredibly rare stuff has happened basically infinitely many times. Life everywhere, etc. Only…it's actually not that old, we have some idea how big it is (not that big, just lots of space between atoms), and thanks to computer science, we're pretty good at analyzing issues surrounding computation complexity. And as it turns out, the DNA-to-protein pathway is much much much less likely that our initial hand waving made it seem. I'm not saying it didn't happen, I'm saying with our current level of knowledge we have no idea how. The math based around being old and big doesn't work. So we need better math, more studies, etc. and less hand waving.
  - chmod775 6y ago
    >Ergo, incredibly rare stuff has happened basically infinitely many times. This wasn't my argument though. In fact it was the complete opposite. I was proposing that it was in fact likely and thus pretty much guaranteed to happen in a large universe, as opposed to being unlikely but still likely given a large enough universe. So we're working with different assumptions here. In fairness I put my assumption way at the beginning of my post, so it probably got forgotten about by the end of it. Quoting myself: > What if amino acids and proteins are in fact likely to arise naturally and in favorable circumstances? We haven't yet conclusively found all of the pathways these can arise, and we continue to discover more. People just tend to assume it's pretty unlikely. I'm not so sure.
    - erichocean 6y ago
      Comparing amino acids to proteins is a category error, almost akin to comparing individual x86 instructions to a full x86 Linux kernel binary. The level of complexity increase is not just in size, but it's a fundamental different thing altogether. The amount of information (via DNA) needed to create a useful protein from the 20 amino acids is absolutely incredible. So…finding more potential (note: not demonstrated) pathways to create amino acids ex nihilo does literally nothing for producing viable DNA strands and proteins. DNA and proteins are a totally different problem, and we've made basically no progress at all, and the more we look at it, the less likely it seems. And then people (not you per se) hand wave about the size of the Universe to explain the problem away. I think we should instead accept the problem exists and work to solve it. ---- Separately, we have no known examples of any natural process producing what we, as humans, would call "information." DNA is much closer to information than any other concept, to the point where if we were sent something similar to DNA from space in, say, a radio transmission, we would absolutely assume intelligent life had made that transmission. That is, with our current knowledge, it takes something vaguely "intelligent" to product the kind of information we have in DNA. Maybe such processes exist, but this is an absolute far cry from producing amino acids from chemical precursors, which are not information-like at all (and thus, it is unsurprising that we can do it).
bserge 6y ago
Fascinating. And of all life on Earth, how did human consciousness arise? We're basically virtual machines/entities/minds stuck inside biological bodies, and the majority of us are at odds with nature and every other living organism on Earth. I guess I'm more interested in how that happened than how life started, both seem equally incomprehensible to me, though.
- Glorbutron 6y ago
  I've seen postulated mechanisms by which increasing levels of self modeling get selected for, demystifying paradoxes has some examples.
gus_massa 6y ago
> It's extremely difficult to produce useful proteins from random DNA chains. I think we all agree about that. > Scientists who have done the math disagree. It's a major current issue. The problem is that you can do the correct calculation or a wrong calculation. For example the number 160 is probably too high. Some of the current proteins have a 160 or more amino acids, but there are shorter proteins, and there are some useful short amino acid chains with only 20 amino acids.
mortehu 6y ago
But why assume a leap directly to proteins, by definition a long chain of amino acids? Couldn't we have started with self-replicating peptides and incremental improvements?
- erichocean 6y ago
  Peptides are just short proteins, and no, we have no idea how to get them either (though it's obviously easier). Also, it's not that what I've called bad/garbage DNA doesn't produce proteins, it's that the proteins produced are useless: they don't "do" anything. There's no obvious reason why DNA "extension" should produce useful proteins over un-useful ones, at least, no mechanism that we have discovered so far. Instead of accepting a theory of incremental improvement that "sounds nice", waving our arms about random chance and an old, vast Universe and going "yup, that's how it happened!", let's try to develop testable mechanisms and validate them. I'm asking for more rigor while simultaneously shooting down "random chance", "plenty of time", and hand waving about the Law of Large Numbers. We've done the math and we need far more effective, directed mechanisms than random chance to produce useful DNA sequences.
  - mortehu 6y ago
    > Peptides are just short proteins This is very misleading. Proteins are defined by a minimum level of complexity, being strictly higher than peptides.
Cogito 6y ago
The framing you have here is an attractive one, but I don't think it makes much sense in the context of reproducing molecules. There is no reason to posit random DNA chains. The statement that "the number of DNA chains that produce valid/useful protein in the space of all possible DNA chains is vanishingly small" seems reasonable (however I'm not sure how we would know these chains are the only ones that produce valid/useful proteins). The idea that we need to choose randomly from the space of all possible DNA chains is not reasonable. ---- Once we have a reproducing molecule, we expect to see a multitude of valid reproducing molecules as descendants of that first molecule. We expect (at least some of) these descendants to eventually be extremely different from the original molecule, and by their nature valid reproducing molecules. Once we have a reproducing molecule (like DNA) that creates other molecules (like RNA and proteins) we can expect the same of its descendants, and the descendants' by-products. If these molecules form an ecosystem, where the reproduction of one relies on the validity of the other, the only succesful variations within the ecosystem will be valid variations of the ecosystem. ---- The space that we are choosing from is not the space of all possible DNA chains, it is the space of all DNA chains adjacent to existing valid chains (or chains in a valid ecosystem). It's analogous to taking a valid x86 program that can reproduce, randomly adding/removing/mutating some bits on reproduction (with low frequency, very quickly, and in a ginormous space - think on the scale of molecules in the Earth's oceans), and asking if that new program is also valid. And then, after millions of years of this, asking if one of the programs is a valid mathematical function. ---- There are still big questions here. Questions like "how do we get the first reproducing molecule?" and "is DNA likely to arise once you have reproducing molecules, or just one out of many options?" None of those questions give reason to evoke the number of all possible variations of DNA as evidence that the variation we see in proteins is somehow unlikely. Once we know that there exists one valid DNA/protein system (which we do, as it exists), and we know that variations of DNA/protein ecosystems can be functional (which we do, as we've observed it), it is reasonable to expect a multitude of valid, functional DNA chains, and the proteins produced by them.
- erichocean 6y ago
  Like you, I can imagine hundreds—maybe thousands—of ways to resolve these issues. That's hardly relevant though, what matters are resolutions that actually work. I agree that we are (very) likely to find the mechanisms involved, but so far, we haven't. In fact, we don't even have a theory on how DNA was originally developed, or how non-functional DNA/proteins self-replicate, or really anything at all. We only have the end product (which does—as you point out—work). The question is how did it get there, and previous hand waving about a huge, old Universe and random chance isn't sufficient. It's going to have to be something similar to what you (and other commenters) describe: mechanisms that preferentially and relatively quickly produce valid, self-replicating DNA/protein chains. To date, no one has found anything even close to that.
Glorbutron 6y ago
You do realize that natural selection iterates through these same sorts of garbage proteins at a rate of trillions and trillions of bacteria per year for millions of years?, and with bias toward previously existing functional structures? It's a pretty potent optimization process, given the timeframes and scale. and the uncertainty is enough. It isn't equivalent to that, because there can also be incremental progress made toward a functional protein, unlike code.
- girvo 6y ago
  Doesn't that presuppose we already _have_ life, and thus is irrelevant to the question, or am I misunderstanding?
  - Cogito 6y ago
    There is a question of where does the first self-replicating molecule come from, and how do we get to DNA from that, and how do we get the diversity of proteins that we see today. Creating random DNA sequences and showing they don't produce 'useful' proteins has nothing to do with any of those questions (and how do we even know they are not useful?)
    - vagrantJin 6y ago
      I think the main stumbling block for me is the perception of time scales. It is impossible for me to say, with certainty, any information regarding time scales of a billion years and the randomness which permeates the evolutionary process. What we see and know are the winners of the race, not the mountains of failures.
ajuc 6y ago
> if I took all of the atoms IN OUR GALAXY There's between 100 and 200 billion galaxies in the observable universe. There were billions of years to do the choosing - how many times per minute am I allowed to do it? > The human body contains between 80,000 and 400,000 proteins. Good thing first life wasn't homo sapiens then (and probably wasn't using DNA).
cma 6y ago
The many worlds interpretation of quantum mechanics increases the combinatorial space to play in for some otherwise unlikely seed event by tremendous amounts. Also, we know stuff like the smallest observed polymerase, but we don't know what the smallest functional one would be that could have into it. We also have self-replicating pure RNA systems, though the components aren't abundant. But this is just what scientists came up with in one effort trying to make one to prove it is feasible: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652413/#R7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652413/#R7

sveme 6y ago

Well, that's why an RNA first world is most likely. RNA can act catalytically as RNAzymes.

chmod775 6y ago

This assumes a perfect random distribution though. What if amino acids and proteins are in fact likely to arise naturally and in favorable circumstances? There was an article recently (~1-2 months) on HN about a supercomputer/AI discovering new chemical pathways for part of this process, but I can't seem to find it anymore. I think it was about forming amino acids. I'm no expert on this subject (the opposite really, I've slept through chemistry), but my experience with large-scale simulations has been that a surprising number of them converge to the same final result given the same starting parameters even if most processes within them are perfectly random. The bigger the simulation, the more likely they are to give you stable results. And the universe is pretty damn huge. So I like to believe the creation of the foundations of life is in fact more-or-less inevitable in our universe, in turn increasing the chance of useful proteins etc. forming.

erichocean 6y ago
> And the universe is pretty damn huge. And that kind of hand-wavey statement seems to convince most people. Universe is hella-old, and really big. Ergo, incredibly rare stuff has happened basically infinitely many times. Life everywhere, etc. Only…it's actually not that old, we have some idea how big it is (not that big, just lots of space between atoms), and thanks to computer science, we're pretty good at analyzing issues surrounding computation complexity. And as it turns out, the DNA-to-protein pathway is much much much less likely that our initial hand waving made it seem. I'm not saying it didn't happen, I'm saying with our current level of knowledge we have no idea how. The math based around being old and big doesn't work. So we need better math, more studies, etc. and less hand waving.
- chmod775 6y ago
  >Ergo, incredibly rare stuff has happened basically infinitely many times. This wasn't my argument though. In fact it was the complete opposite. I was proposing that it was in fact likely and thus pretty much guaranteed to happen in a large universe, as opposed to being unlikely but still likely given a large enough universe. So we're working with different assumptions here. In fairness I put my assumption way at the beginning of my post, so it probably got forgotten about by the end of it. Quoting myself: > What if amino acids and proteins are in fact likely to arise naturally and in favorable circumstances? We haven't yet conclusively found all of the pathways these can arise, and we continue to discover more. People just tend to assume it's pretty unlikely. I'm not so sure.
  - erichocean 6y ago
    Comparing amino acids to proteins is a category error, almost akin to comparing individual x86 instructions to a full x86 Linux kernel binary. The level of complexity increase is not just in size, but it's a fundamental different thing altogether. The amount of information (via DNA) needed to create a useful protein from the 20 amino acids is absolutely incredible. So…finding more potential (note: not demonstrated) pathways to create amino acids ex nihilo does literally nothing for producing viable DNA strands and proteins. DNA and proteins are a totally different problem, and we've made basically no progress at all, and the more we look at it, the less likely it seems. And then people (not you per se) hand wave about the size of the Universe to explain the problem away. I think we should instead accept the problem exists and work to solve it. ---- Separately, we have no known examples of any natural process producing what we, as humans, would call "information." DNA is much closer to information than any other concept, to the point where if we were sent something similar to DNA from space in, say, a radio transmission, we would absolutely assume intelligent life had made that transmission. That is, with our current knowledge, it takes something vaguely "intelligent" to product the kind of information we have in DNA. Maybe such processes exist, but this is an absolute far cry from producing amino acids from chemical precursors, which are not information-like at all (and thus, it is unsurprising that we can do it).

bserge 6y ago

Fascinating. And of all life on Earth, how did human consciousness arise? We're basically virtual machines/entities/minds stuck inside biological bodies, and the majority of us are at odds with nature and every other living organism on Earth. I guess I'm more interested in how that happened than how life started, both seem equally incomprehensible to me, though.

Glorbutron 6y ago
I've seen postulated mechanisms by which increasing levels of self modeling get selected for, demystifying paradoxes has some examples.

gus_massa 6y ago

> It's extremely difficult to produce useful proteins from random DNA chains. I think we all agree about that. > Scientists who have done the math disagree. It's a major current issue. The problem is that you can do the correct calculation or a wrong calculation. For example the number 160 is probably too high. Some of the current proteins have a 160 or more amino acids, but there are shorter proteins, and there are some useful short amino acid chains with only 20 amino acids.

mortehu 6y ago

But why assume a leap directly to proteins, by definition a long chain of amino acids? Couldn't we have started with self-replicating peptides and incremental improvements?

erichocean 6y ago
Peptides are just short proteins, and no, we have no idea how to get them either (though it's obviously easier). Also, it's not that what I've called bad/garbage DNA doesn't produce proteins, it's that the proteins produced are useless: they don't "do" anything. There's no obvious reason why DNA "extension" should produce useful proteins over un-useful ones, at least, no mechanism that we have discovered so far. Instead of accepting a theory of incremental improvement that "sounds nice", waving our arms about random chance and an old, vast Universe and going "yup, that's how it happened!", let's try to develop testable mechanisms and validate them. I'm asking for more rigor while simultaneously shooting down "random chance", "plenty of time", and hand waving about the Law of Large Numbers. We've done the math and we need far more effective, directed mechanisms than random chance to produce useful DNA sequences.
- mortehu 6y ago
  > Peptides are just short proteins This is very misleading. Proteins are defined by a minimum level of complexity, being strictly higher than peptides.

Cogito 6y ago

The framing you have here is an attractive one, but I don't think it makes much sense in the context of reproducing molecules. There is no reason to posit random DNA chains. The statement that "the number of DNA chains that produce valid/useful protein in the space of all possible DNA chains is vanishingly small" seems reasonable (however I'm not sure how we would know these chains are the only ones that produce valid/useful proteins). The idea that we need to choose randomly from the space of all possible DNA chains is not reasonable. ---- Once we have a reproducing molecule, we expect to see a multitude of valid reproducing molecules as descendants of that first molecule. We expect (at least some of) these descendants to eventually be extremely different from the original molecule, and by their nature valid reproducing molecules. Once we have a reproducing molecule (like DNA) that creates other molecules (like RNA and proteins) we can expect the same of its descendants, and the descendants' by-products. If these molecules form an ecosystem, where the reproduction of one relies on the validity of the other, the only succesful variations within the ecosystem will be valid variations of the ecosystem. ---- The space that we are choosing from is not the space of all possible DNA chains, it is the space of all DNA chains adjacent to existing valid chains (or chains in a valid ecosystem). It's analogous to taking a valid x86 program that can reproduce, randomly adding/removing/mutating some bits on reproduction (with low frequency, very quickly, and in a ginormous space - think on the scale of molecules in the Earth's oceans), and asking if that new program is also valid. And then, after millions of years of this, asking if one of the programs is a valid mathematical function. ---- There are still big questions here. Questions like "how do we get the first reproducing molecule?" and "is DNA likely to arise once you have reproducing molecules, or just one out of many options?" None of those questions give reason to evoke the number of all possible variations of DNA as evidence that the variation we see in proteins is somehow unlikely. Once we know that there exists one valid DNA/protein system (which we do, as it exists), and we know that variations of DNA/protein ecosystems can be functional (which we do, as we've observed it), it is reasonable to expect a multitude of valid, functional DNA chains, and the proteins produced by them.

erichocean 6y ago
Like you, I can imagine hundreds—maybe thousands—of ways to resolve these issues. That's hardly relevant though, what matters are resolutions that actually work. I agree that we are (very) likely to find the mechanisms involved, but so far, we haven't. In fact, we don't even have a theory on how DNA was originally developed, or how non-functional DNA/proteins self-replicate, or really anything at all. We only have the end product (which does—as you point out—work). The question is how did it get there, and previous hand waving about a huge, old Universe and random chance isn't sufficient. It's going to have to be something similar to what you (and other commenters) describe: mechanisms that preferentially and relatively quickly produce valid, self-replicating DNA/protein chains. To date, no one has found anything even close to that.

Glorbutron 6y ago

You do realize that natural selection iterates through these same sorts of garbage proteins at a rate of trillions and trillions of bacteria per year for millions of years?, and with bias toward previously existing functional structures? It's a pretty potent optimization process, given the timeframes and scale. and the uncertainty is enough. It isn't equivalent to that, because there can also be incremental progress made toward a functional protein, unlike code.

girvo 6y ago
Doesn't that presuppose we already _have_ life, and thus is irrelevant to the question, or am I misunderstanding?
- Cogito 6y ago
  There is a question of where does the first self-replicating molecule come from, and how do we get to DNA from that, and how do we get the diversity of proteins that we see today. Creating random DNA sequences and showing they don't produce 'useful' proteins has nothing to do with any of those questions (and how do we even know they are not useful?)
  - vagrantJin 6y ago
    I think the main stumbling block for me is the perception of time scales. It is impossible for me to say, with certainty, any information regarding time scales of a billion years and the randomness which permeates the evolutionary process. What we see and know are the winners of the race, not the mountains of failures.

ajuc 6y ago

> if I took all of the atoms IN OUR GALAXY There's between 100 and 200 billion galaxies in the observable universe. There were billions of years to do the choosing - how many times per minute am I allowed to do it? > The human body contains between 80,000 and 400,000 proteins. Good thing first life wasn't homo sapiens then (and probably wasn't using DNA).

cma 6y ago

The many worlds interpretation of quantum mechanics increases the combinatorial space to play in for some otherwise unlikely seed event by tremendous amounts. Also, we know stuff like the smallest observed polymerase, but we don't know what the smallest functional one would be that could have into it. We also have self-replicating pure RNA systems, though the components aren't abundant. But this is just what scientists came up with in one effort trying to make one to prove it is feasible: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652413/#R7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652413/#R7