The RNA World Hypothesis(ncbi.nlm.nih.gov)
ncbi.nlm.nih.gov
The RNA World Hypothesis
https://www.ncbi.nlm.nih.gov/books/NBK26876/
7 comments
How is it simultaneously possible to be a personal friend to someone and not have had the opportunity to interact with that person?
You and I were probably the only folks who recommended this book in HN history so hi! Totally agreed that this is required reading for anyone interested in learning about modern science on evolution (as opposed to the Dawkins drivel)
What's wrong with Dawkins (aside from him being an ass)?
I've looked on Google Books' preview and it reads quite smoothly.
I was surprised that Google's price is so much lower than Amazon's though? Less than a half? (Might be locale-dependent, I'm in Poland). It has been long since I bought anything on Google, but I assume it can still be converted to a DRM-free epub like described here?: https://www.reddit.com/r/kindle/comments/3menci/i_prefer_my_...
Where's the catch?
I was surprised that Google's price is so much lower than Amazon's though? Less than a half? (Might be locale-dependent, I'm in Poland). It has been long since I bought anything on Google, but I assume it can still be converted to a DRM-free epub like described here?: https://www.reddit.com/r/kindle/comments/3menci/i_prefer_my_...
Where's the catch?
Love the way you write--"It interrogates virtually every hypothesis" <-- terrific
You might also like the work of Collizi and Hogeweg. They did some rather interesting theoretical work on RNA world hypotheses, particularly on the issue of the error threshold.
About virology, there is no doubt that the first RNA molecule was a virus.
All the popular presentations about the "RNA world" are either incomplete and/or logically inconsistent.
There certainly was a RNA world, in the sense of a world where there was no DNA, but only RNA.
However, there must have existed 2 stages of the RNA world, the later stage, when protein synthesis based on translation from RNA existed, like today, and also an earlier stage, when only RNA replication existed, but RNA did not perform any useful function for its host living being, but it was only a virus that was replicated using energy and molecular components from its host.
The fact that there are RNA molecules that can have a catalytic effect like enzymes, as mentioned in the article is completely irrelevant. If such catalytic RNA molecules had ever existed before the apparition of RNA replication, they would have immediately disappeared without living any descendants.
Only from the moment when some self-replicating RNA molecules has appeared, i.e. the first virus, we have some chain of nucleic acid replications, which has continued until today and all the existing nucleic acid molecules must be descendants of the first virus.
The first replicating RNA molecule required for its synthesis energy and molecular components, in the form of ATP and free nucleotides, which can condense into RNA.
So there must have already existed an equivalent of a bacteria, with metabolism using energy from the environment (i.e. dihydrogen with carbon dioxide and ionic gradients), which was already able to make ATP, which would have been needed to synthesize the polymers made by condensation, e.g. peptides. The apparition of the first RNA virus was an initially undesirable side-effect of using ATP to perform polymer condensations.
Because any memory molecule, like RNA, needs an already existing living being for its first replication, there must have been a stage prior to the RNA world, when there were self-replicating living beings, but without memory molecules.
The self-replication of a system does not need a memory, it can be "hard-wired", where there is a closed chain of chemical reactions where each reaction synthesizes a new component based on previous components and eventually the first component is synthesized from the last components.
However such a self-replicating system without a memory had extremely low chances of evolution, because any random change was almost certain to break the self-replication cycle, leading to death without descendants.
Only after the apparition of RNA, and especially after the later appearance of the RNA to protein translation mechanism, it became possible for mutations to accumulate and eventually create a variety of living beings.
While the first RNA must have been a virus, because diverting ATP and other useful internal components to the production of RNA molecules could not have been of any good for the host, some time after the apparition of RNA-based protein synthesis, some form of symbiosis between a host and some DNA virus must have created the ancestors of bacteria.
All the popular presentations about the "RNA world" are either incomplete and/or logically inconsistent.
There certainly was a RNA world, in the sense of a world where there was no DNA, but only RNA.
However, there must have existed 2 stages of the RNA world, the later stage, when protein synthesis based on translation from RNA existed, like today, and also an earlier stage, when only RNA replication existed, but RNA did not perform any useful function for its host living being, but it was only a virus that was replicated using energy and molecular components from its host.
The fact that there are RNA molecules that can have a catalytic effect like enzymes, as mentioned in the article is completely irrelevant. If such catalytic RNA molecules had ever existed before the apparition of RNA replication, they would have immediately disappeared without living any descendants.
Only from the moment when some self-replicating RNA molecules has appeared, i.e. the first virus, we have some chain of nucleic acid replications, which has continued until today and all the existing nucleic acid molecules must be descendants of the first virus.
The first replicating RNA molecule required for its synthesis energy and molecular components, in the form of ATP and free nucleotides, which can condense into RNA.
So there must have already existed an equivalent of a bacteria, with metabolism using energy from the environment (i.e. dihydrogen with carbon dioxide and ionic gradients), which was already able to make ATP, which would have been needed to synthesize the polymers made by condensation, e.g. peptides. The apparition of the first RNA virus was an initially undesirable side-effect of using ATP to perform polymer condensations.
Because any memory molecule, like RNA, needs an already existing living being for its first replication, there must have been a stage prior to the RNA world, when there were self-replicating living beings, but without memory molecules.
The self-replication of a system does not need a memory, it can be "hard-wired", where there is a closed chain of chemical reactions where each reaction synthesizes a new component based on previous components and eventually the first component is synthesized from the last components.
However such a self-replicating system without a memory had extremely low chances of evolution, because any random change was almost certain to break the self-replication cycle, leading to death without descendants.
Only after the apparition of RNA, and especially after the later appearance of the RNA to protein translation mechanism, it became possible for mutations to accumulate and eventually create a variety of living beings.
While the first RNA must have been a virus, because diverting ATP and other useful internal components to the production of RNA molecules could not have been of any good for the host, some time after the apparition of RNA-based protein synthesis, some form of symbiosis between a host and some DNA virus must have created the ancestors of bacteria.
> So there must have already existed an equivalent of a bacteria, with metabolism using energy from the environment (i.e. dihydrogen with carbon dioxide and ionic gradients), which was already able to make ATP, which would have been needed to synthesize the polymers made by condensation, e.g. peptides. The apparition of the first RNA virus was an initially undesirable side-effect of using ATP to perform polymer condensations.
No, you're not postulating an RNA world here. The whole point of the RNA world (aka "RNA first") hypothesis is that the first life (self-contained, self-replicating particles) was RNA-based, and both proteins and lipid bilayers came later. If you argue that the first RNA was a virus that parasitized already existing organisms, then it's usually called a "metabolism first" hypothesis.
No, you're not postulating an RNA world here. The whole point of the RNA world (aka "RNA first") hypothesis is that the first life (self-contained, self-replicating particles) was RNA-based, and both proteins and lipid bilayers came later. If you argue that the first RNA was a virus that parasitized already existing organisms, then it's usually called a "metabolism first" hypothesis.
Yes, that is exactly that what I have said.
While there was replicating RNA before any DNA and before any proteins made by translation from RNA, metabolism must have existed before any RNA and catalysis must have been done with peptides produced by other ways than translation from RNA (today there still are such non-ribosomal peptides).
Speaking about a RNA world is correct only in this sense, because RNA could not have performed any function before a mechanism for its replication had appeared and such a mechanism could not appear in any environment where ATP and the other nucleotides did not already exist.
ATP and the other nucleotides could not be made without an already functioning metabolism.
On the other hand, there is absolutely no need of RNA or of any other memory molecule for a working metabolism.
These precedence relations are as certain as 2 + 2 = 4, so speaking of any other kind of RNA world is senseless, despite the fact that there have been indeed many publications that fail to mention why the appearance of RNA before ATP and before metabolism is impossible.
While there was replicating RNA before any DNA and before any proteins made by translation from RNA, metabolism must have existed before any RNA and catalysis must have been done with peptides produced by other ways than translation from RNA (today there still are such non-ribosomal peptides).
Speaking about a RNA world is correct only in this sense, because RNA could not have performed any function before a mechanism for its replication had appeared and such a mechanism could not appear in any environment where ATP and the other nucleotides did not already exist.
ATP and the other nucleotides could not be made without an already functioning metabolism.
On the other hand, there is absolutely no need of RNA or of any other memory molecule for a working metabolism.
These precedence relations are as certain as 2 + 2 = 4, so speaking of any other kind of RNA world is senseless, despite the fact that there have been indeed many publications that fail to mention why the appearance of RNA before ATP and before metabolism is impossible.
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>such a mechanism could not appear in any environment where ATP and the other nucleotides did not already exist.
What evidence is there that this is true
What evidence is there that this is true
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>and also an earlier stage, when only RNA replication existed, but RNA did not perform any useful function for its host living being, but it was only a virus that was replicated using energy and molecular components from its host.
And in this stage, where there is no DNA, what molecule carried the genetic information of these host organisms?
>Because any memory molecule, like RNA, needs an already existing living being for its first replication
No, it doesn't. RNA is capable of folding into complex catalytic machineries same as polypeptide chains (aka. proteins). An RNA synthetase itself composed of RNA is absolutely probable.
And in this stage, where there is no DNA, what molecule carried the genetic information of these host organisms?
>Because any memory molecule, like RNA, needs an already existing living being for its first replication
No, it doesn't. RNA is capable of folding into complex catalytic machineries same as polypeptide chains (aka. proteins). An RNA synthetase itself composed of RNA is absolutely probable.
As I have already said, there is no need for genetic information in a living being able to grow and reproduce.
The difference between a living being with genetic information and a living being without genetic information is the same as between a processor with micro-programmed control and a processor with hard-wired control.
In a processor with micro-programmed control, it is easy to add new instructions or to replace the instructions that it can execute with others having a completely different behavior, just by changing the content of the control memory.
In a processor with hard-wired control, you might be able to change the interconnections between blocks or to replace some logical gates with other kinds of logical gates, but the chances that these changes will result in a new processor that will still function and do something useful are minuscule.
Genetic information is necessary for the evolution of simple self-reproducing living beings to the complex living beings that exist today, but it is not necessary for life, i.e. for growth and reproduction of complex molecules.
It is fortunate that this is true, because otherwise there would have not been any path from inanimate matter to memory molecules like RNA, because they cannot continue to exist without being replicated from the template of an already existing memory molecule, so they cannot have any other function earlier than the first replication begins to produce them, and the replication cannot appear before the monomers, e.g. ATP, are available.
About the RNA synthetase, that is just a catalyst.
It cannot produce any RNA without the monomers (nucleotides) and without energy, i.e. a dehydrating agent like ATP, which must extract the water from the monomers, to condense them in the RNA polymer.
In the first living beings that used ATP and the other nucleotides to perform condensation reactions, the reactions were not controlled as well as today, so there were many parasite reactions that consumed a part of the reactants instead of producing the desirable end products. So some of the ATP molecules must have condensed with themselves and with other nucleotides, instead of producing useful polymers.
From these ATP condensation side-reactions, some kind of RNA synthetase must have been produced by chance and then it began to replicate itself. However that was possible only because ATP and nucleotides produced continuously by the host metabolism were available. Without monomers, the RNA synthetase would not have been able to do anything.
The difference between a living being with genetic information and a living being without genetic information is the same as between a processor with micro-programmed control and a processor with hard-wired control.
In a processor with micro-programmed control, it is easy to add new instructions or to replace the instructions that it can execute with others having a completely different behavior, just by changing the content of the control memory.
In a processor with hard-wired control, you might be able to change the interconnections between blocks or to replace some logical gates with other kinds of logical gates, but the chances that these changes will result in a new processor that will still function and do something useful are minuscule.
Genetic information is necessary for the evolution of simple self-reproducing living beings to the complex living beings that exist today, but it is not necessary for life, i.e. for growth and reproduction of complex molecules.
It is fortunate that this is true, because otherwise there would have not been any path from inanimate matter to memory molecules like RNA, because they cannot continue to exist without being replicated from the template of an already existing memory molecule, so they cannot have any other function earlier than the first replication begins to produce them, and the replication cannot appear before the monomers, e.g. ATP, are available.
About the RNA synthetase, that is just a catalyst.
It cannot produce any RNA without the monomers (nucleotides) and without energy, i.e. a dehydrating agent like ATP, which must extract the water from the monomers, to condense them in the RNA polymer.
In the first living beings that used ATP and the other nucleotides to perform condensation reactions, the reactions were not controlled as well as today, so there were many parasite reactions that consumed a part of the reactants instead of producing the desirable end products. So some of the ATP molecules must have condensed with themselves and with other nucleotides, instead of producing useful polymers.
From these ATP condensation side-reactions, some kind of RNA synthetase must have been produced by chance and then it began to replicate itself. However that was possible only because ATP and nucleotides produced continuously by the host metabolism were available. Without monomers, the RNA synthetase would not have been able to do anything.
>there is no need for genetic information in a living being able to grow and reproduce.
Yes there is, because one of the principles that define life is the ability to "pass traits onto offspring". This isn't possible without a medium to carry that information.
Self replicating systems do not require information. Self replicating systems that are "alive" by any definiton in the scientific literature, do.
>It cannot produce any RNA without the monomers (nucleotides) and without energy, i.e. a dehydrating agent like ATP
In the same way RNA folds could catalyse RNA synthesis, other folding patterns could break down energy-rich compounds and generate nucleotides.
The one thing they need for this to work, is an enclosed reaction environment, aka a lipid-vesicle, which form spotaneously as long as there are fatty acids.
So no, the RNA world does NOT require some form of non-genetic-host-organisms. Folded RNA molecules within lipid vesicles are likely the earliest form of organised life.
Yes there is, because one of the principles that define life is the ability to "pass traits onto offspring". This isn't possible without a medium to carry that information.
Self replicating systems do not require information. Self replicating systems that are "alive" by any definiton in the scientific literature, do.
>It cannot produce any RNA without the monomers (nucleotides) and without energy, i.e. a dehydrating agent like ATP
In the same way RNA folds could catalyse RNA synthesis, other folding patterns could break down energy-rich compounds and generate nucleotides.
The one thing they need for this to work, is an enclosed reaction environment, aka a lipid-vesicle, which form spotaneously as long as there are fatty acids.
So no, the RNA world does NOT require some form of non-genetic-host-organisms. Folded RNA molecules within lipid vesicles are likely the earliest form of organised life.
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Stated Clearly has a great video about the RNA world hypothesis (https://www.youtube.com/watch?v=K1xnYFCZ9Yg) if anyone's looking for an engaging overview.
That was a fantastic video. It gave intuitive explanations to not just the hypothesis itself but how certain biochemical mechanisms function. Thanks for linking it.
I find it funny that the comments here split across:
“I have no doubt that life emerged from an RNA first world”
and
“I have no doubt that life emerged from a metabolism first world”
Last I checked, nobody should have absolute certainty for how life began. Progress comes from skepticism. Have more doubt!
“I have no doubt that life emerged from an RNA first world”
and
“I have no doubt that life emerged from a metabolism first world”
Last I checked, nobody should have absolute certainty for how life began. Progress comes from skepticism. Have more doubt!
Given the instability of ribose even in plain pH 7 water, and the indiscriminate results of abiotic carbohydrate synthesis processes, I find the RNA-first hypothesis unlikely.
https://www.jstor.org/stable/2368016
https://www.jstor.org/stable/2368016
I do not doubt things just to doubt them however. Doubt has to be reasonable.
[0] Self-Sustained Replication of an RNA Enzyme, Tracey A. Lincoln and Gerald F. Joyce
https://www.researchgate.net/publication/23766369_Self-Susta...
https://www.researchgate.net/publication/23766369_Self-Susta...
I have no doubt that our life originally evolved from an RNA world. I’m just not convinced the world is earth. This shit could not have happened so fast (few tens or hundreds of million years?) the moment it became conducive on earth. It must have flown in as archea from elsewhere!
Also anyone who’s worked in a lab trying to keep some Lb plates sterile would immediately see how difficult it would be to keep an earth sized Lb plate sterile if the galaxy has a ton of life harboring planets.
Also anyone who’s worked in a lab trying to keep some Lb plates sterile would immediately see how difficult it would be to keep an earth sized Lb plate sterile if the galaxy has a ton of life harboring planets.
>This shit could not have happened so fast (few tens or hundreds of million years?)
It didn't happen that fast. The earliest direct evidence, (as in: fossils) for life on earth are 3.465 BILLION years old.
https://en.wikipedia.org/wiki/Earliest_known_life_forms
>Also anyone who’s worked in a lab trying to keep some Lb plates sterile would immediately see how difficult it would be to keep an earth sized Lb plate sterile if the galaxy has a ton of life harboring planets.
The earths diameter is 12742 km.
A petri-dish is usually about 12 cm in diameter.
The closest star system (Alpha Centaury) is 9461000000000 km away (4.35 LY).
So the closest place in the galaxy where there is even sufficient mass for conditions to form life, is ~2970020405 earth-diameters from here.
Two petri dishes on opposite sides of the planet are ~106183333 petri-dish-diameters away from each other.
So purely from a perspective of distance, the chance that two petri-dishes on opposite sides of the planet transmit life between them, is an order of magnitude HIGHER than life coming to earth from outer space.
It didn't happen that fast. The earliest direct evidence, (as in: fossils) for life on earth are 3.465 BILLION years old.
https://en.wikipedia.org/wiki/Earliest_known_life_forms
>Also anyone who’s worked in a lab trying to keep some Lb plates sterile would immediately see how difficult it would be to keep an earth sized Lb plate sterile if the galaxy has a ton of life harboring planets.
The earths diameter is 12742 km.
A petri-dish is usually about 12 cm in diameter.
The closest star system (Alpha Centaury) is 9461000000000 km away (4.35 LY).
So the closest place in the galaxy where there is even sufficient mass for conditions to form life, is ~2970020405 earth-diameters from here.
Two petri dishes on opposite sides of the planet are ~106183333 petri-dish-diameters away from each other.
So purely from a perspective of distance, the chance that two petri-dishes on opposite sides of the planet transmit life between them, is an order of magnitude HIGHER than life coming to earth from outer space.
Read your own ref. Optimistic estimates put the first appearance of life on earth as soon as 50 mill years after oceans formed.
The Petri dish analogy was only supposed to be tounge in cheek but if you want to be pedantic then consider that the medium between the source and destination is a frozen vacuum which means you have billions of years for transmission and spreading.
The Petri dish analogy was only supposed to be tounge in cheek but if you want to be pedantic then consider that the medium between the source and destination is a frozen vacuum which means you have billions of years for transmission and spreading.
Yes, and these oceans formed 4.5 billion years ago, aka. much longer than "few tens or hundreds of million years"
> then consider that the medium between the source and destination is a frozen vacuum which means you have billions of years for transmission and spreading.
And by what means does that spreading take place? Spreading implies a medium through which to spread, which doesn't exist in interstellar space.
So that leaves moving over that distance on a fragment of a shattered planetoid for example. The fastest known asteroid, 2021-PH27 clocks at around 106 km/sec. Meaning, it would require about 2800y to make it's journey (remember, this is still alpha centauri I'm talking about, which by all accounts has no planets in the habitable zone).
2800 years at top speed thorugh the vacuum of space, unshielded from the denaturing effects of cosmic radiation. And at the end of that travel, if it isn't swallowed up by the gravitational forces of the sun or our 2 gas giants, an impact event comparable to a large thermonuclear device going off.
Sorry, but compared to that, sponeneous abiogenesis sounds a lot more plausible to me.
> then consider that the medium between the source and destination is a frozen vacuum which means you have billions of years for transmission and spreading.
And by what means does that spreading take place? Spreading implies a medium through which to spread, which doesn't exist in interstellar space.
So that leaves moving over that distance on a fragment of a shattered planetoid for example. The fastest known asteroid, 2021-PH27 clocks at around 106 km/sec. Meaning, it would require about 2800y to make it's journey (remember, this is still alpha centauri I'm talking about, which by all accounts has no planets in the habitable zone).
2800 years at top speed thorugh the vacuum of space, unshielded from the denaturing effects of cosmic radiation. And at the end of that travel, if it isn't swallowed up by the gravitational forces of the sun or our 2 gas giants, an impact event comparable to a large thermonuclear device going off.
Sorry, but compared to that, sponeneous abiogenesis sounds a lot more plausible to me.
Seriously, Read the two sentences immediately after the sentence you got your number from in the Wikipedia page you referred. Earliest estimates go back further.
And where exactly am I talking about "estimates"?
Quote from my post:
Quote from my post:
"The earliest direct evidence,"
> Also anyone who’s worked in a lab trying to keep some Lb plates sterile would immediately see how difficult it would be to keep an earth sized Lb plate sterile if the galaxy has a ton of life harboring planets.
Unless you worked in an enormous vaccuum, I'm not realy sure how that's supposed to be comparable.
Unless you worked in an enormous vaccuum, I'm not realy sure how that's supposed to be comparable.
Copyright 2002. Predates a lot of understanding in molecular genetics. Just sayin'
This is from 2002, the title could probably include that.
I'm admittedly biased, because Koonin is a personal friend and occasional colleague of a member of my PhD committee, but what I've heard from everyone that I know who has interacted with him (unfortunately I've never had the opportunity, to my great dismay), is that he's completely unassuming and carries no ego at all. My experience reading "The Logic of Chance" has confirmed this. The book is accessible to anyone with an ability to read. It taught me more about how to think for myself and recognize bias than probably any other work I've read (perhaps excluding Taleb's "Incerto" series, which complement Koonin's work very nicely), and also taught me a lot about evolution. The book can be found on the usual websites that graduate students are apt to visit.
The RNA world hypothesis is almost single handedly responsible for my interest in virology.