RNA World:

The Answer to Chickens and Eggs

One regret I have regarding the demise of Uncommon Descent is being unable to continue discussion with Upright Biped, a regular at UD who believed he had an argument against the natural evolution of the genetic code, which I refer to as his “semiotic hypothesis”.

Whilst wrapped up in impenetrable jargon and idiosyncratic prose, it is/was quite a simple argument: that the first organisms could not evolve the genetic code without already having the metabolism in place and vice versa, an insoluble chicken-and-egg conundrum.

Upright Biped first publicized his idea in 2011, and it was the subject of an OP by Elizabeth Liddle (owner of this site) in October 2011. 

I didn’t get involved much at the time, as discussion seemed to stick at the semiotics, whereas I thought Upright Biped’s best point was it would be impossible for a genetic storage system to evolve prior to metabolism and equally for heritable metabolic pathways to evolve without a genetic storage system. A classical chicken and egg issue.

In 2005, I encountered the late Robert Shapiro (over his alleged peer review of Mike Behe’s Darwin’s Black Box) who was a sceptic on RNA World, and he influenced me to adopt the same view. Anyway, Upright Biped continued sporadically to promote his idea at Uncommon Descent and elsewhere without much success, yet I thought the “which first, genetic code or metabolism” conundrum was a strong argument.

Not least due to the input from erstwhile TSZ regular, Allan Miller, I have since changed my mind about RNA World and now find it a plausible idea, and there is more and increasing evidentiary support for RNA World than I knew of in 2005 and 2011.

The brilliant thing about RNA World is that RNA can act as a gene, in that it can and does act as a template for replication and also RNA is capable of being a catalyst, a ribozyme, the RNA equivalent of a protein enzyme. Indeed, RNA is the catalytic heart of cellular metabolic “machinery” that synthesizes proteins, the ribosome. No chickens and no eggs, and critically, no genetic code needed. 

I should put in a word for Nick Lane here, whose UCL research group have published many papers on the origin of life from a biochemical standpoint. I recently bought his book, Transformer: The Deep Chemistry of Life and Death, which I recommend as a good summary of the current state of play without being overly technical. There’s a good video of a recent talk here for a recent overview.

I’ve contributed a fair few comments to Uncommon Descent over the years, and been banned a few times, culminating in my disappearance under the pseudonym, Aurelio Smith, back in 2015, since when I’d been content to lurk until, last year I noticed Upright Biped addressing comments to an ID sceptic, JVL, promoting his semiotic argument again. JVL is a mathematician and Upright Biped seemed to have fixated on JVL to the extent of harassing him. So I registered under the pseudonym, Fred Hickson, and added my 2¢.

Unfortunately, force majeure has prevented the discussion with Upright Biped continuing so I hope he’ll consider joining us here. 

 

 

 

254 thoughts on “RNA World:

  1. Elizabeth:
    “CharlieM: Yes, I’m speculating. I do know that I dream and the vast majority of my dreams are not retained in my consciousness, if they ever reach my consciousness in the first place.

    I haven’t looked into it but regression through hypnosis might shed some light on consciousness during anaesthesia.”

    Elizabeth: I think you touch on an important point here. My own take is that memory is intrinsic to conciouness. In fact, I would go so far as to say that “consciousness” isn’t something we “have” (or concious something we “are”) but something we do – and to make sense of it it needs an object – what are we conscious OF?

    And much of the time what are conscious OF is not just the present, but how it relates to memories of the past. So we might be conscious of the present (and even of the past) during a lucid period under anaesthetic, but on “waking” we are not conscious of that conscious period – and it may remain permanently inaccessible to our “consciousness”, or, as I would prefer to term it “our conscious awareness”, though it may leave a trace in the way we react or behave.

    Yes, and “our conscious awareness” is not like an on/off switch. It assumes various levels. And I would say this can be in both directions, enhanced and diminished from our normal waking consciousness.

    If anyone experiences a moment of extreme trauma they are often aware of time slowing down so that, as it happens, they are cognizant of the event in great detail.

  2. CharlieM: I would say he is using the methods of contemporary natural science, which comes from within an ‘onlooker consciousness’.

    I do not think this is at all true: the methods of contemporary natural science do not involve an “onlooker consciousness”. Contemporary natural science involves active intervention into the causal flux by way of experimentation and manipulation. Even observation in field work involves a great deal of decision-making about what to measure and how. All intervention involves interaction (or, better, what Karen Barad calls “intra-action”).

    This stems from the dualistic Res extensa and res cogitans of Descartes which is difficult to escape from.

    I think it is quite easy to escape from once the dualism is correctly understood. But most people do not correctly understand the source of Cartesian dualism because they just haven’t taken the time to read Descartes’s original works carefully.

    How can the non-physical, ‘something’ that is missing any physical attributes, affect the physical? Isn’t that what he’s asking?

    No, I don’t think it is. He is talking about the causal power of absences. That is different from posting something that is actually present, yet non-physical.

  3. ***Drive-by comment alert!***

    Coming late to this, and it seems to have gone into tangential fields already, but one thing I think deeply significant to the OP is the role of RNA monomers in cellular energetics. ATP we all know about if we paid attention in biology class, but GTP has a vital role in (for significant example) protein synthesis, while CTP and UTP* also find roles in some quite fundamental biochemistry.

    Additionally, the Adenosine moiety with various numbers of attached phosphates appears in several other forms quite central to biochemistry: NAD(H), FAD, Coenzyme A, and others.

    What gives?

    As far as the unadulterated monomers are concerned, there are 3 parts: the planar bases ACUG that some seek to dignify as a ‘code’, ribose and 3 phosphates.

    For energetic purposes, the business end is those 3 phosphates. Cleavage of these yields energy. Now, among the energetic processes utilising this fact are the nucleic acid chain extension processes themselves: RNA and DNA polymerisation. But you don’t just chain ribose-phosphates together. In order for stacking to take place, you need the bases: the A, U, C and G. Further, those bases need to be complementary – A pairs with U, G with C (but only when the chains are oriented antiparallel). Without that, you have no hope of replication, nor indeed of protein synthesis, proofreading**, repair, or any other process that utilises complementarity.

    So, we can see that the base does have a role in chain extension and other templated/binding actions. But what’s it doing when xTP is a cofactor, or part of one? Sure, it can act as a ‘handle’ for enzymes to grab onto. But why does that handle have an antiparallel complement; why is it planar; why does it happen to stack so neatly when the 3′ carbon of one ribose links, with the release of energy, to the 5” of its neighbour?

    My money: the fundamental reaction is RNA polymerisation. All the rest is just repurposing what was already there.

    *UTP but not, as far as I can gather, TTP. Eeenteresting, no? dTTP being the DNA version of RNA’s UTP an’ all. Almost as if one of them was late to the party…

    ** “He said proofreading! Even in denial he’s using linguistic terms!” Calm yourself.

  4. Allan Miller: Additionally, the Adenosine moiety with various numbers of attached phosphates appears in several other forms quite central to biochemistry: NAD(H)…

    I’m reading Nick Lane’s Transformer in which he has quite a bit to say about NADH especially in relation to the Krebs cycle. I have to confess I didn’t follow his points well enough to précis them so I’ll have another read of the relevant chapters.

  5. Alan Fox,

    Cheers! I am yet again on a long-distance hike: the Pacific Crest Trail. Just come out of the Sierra Nevada to Mammoth, in a record snow year. Epic!

  6. Alan Fox,

    I’m reading Nick Lane’s Transformer in which he has quite a bit to say about NADH especially in relation to the Krebs cycle. I have to confess I didn’t follow his points well enough to précis them so I’ll have another read of the relevant chapters.

    Haven’t read that one (though I think Lane explains biochemistry well) but a key point for me is that adenosine appears in those modified forms, typically as a dinucleotide, or as ATP etc when a cofactor, in exactly the same form as in an RNA helix. There is no apparent energetic reason for this. If you’re going to donate or receive electrons, or release the energy of phosphate cleavage, you don’t need a flat molecule that hydrogen-bonds with another (only when ‘upside down’) and is capable of mutual template specification through that complementarity.

    You wouldn’t do it like that. You’d optimise for the job in hand: a planar base for a neat stereochemical fit, or some other moiety for optimal energetics. It smacks of co-option of preexisting components.

  7. Allan Miller:
    Alan Fox,

    Cheers! I am yet again on a long-distance hike: the Pacific Crest Trail. Just come out of the Sierra Nevada to Mammoth, in a record snow year. Epic!

    Bloody hell!! All of it? To say I’m impressed would be an understatement.

  8. Allan Miller,

    We’ve been invaded by nieces, so today is dedicated to sybaritic pursuits involving swimming pools and barbecues, making substantive comments more difficult than normal. I imagine there are similar distractions in Mammoth. 😉

  9. Allan Miller: You wouldn’t do it like that. You’d optimise for the job in hand: a planar base for a neat stereochemical fit, or some other moiety for optimal energetics. It smacks of co-option of preexisting components.

    Designer is just trying to fool us.

  10. Allan Miller: If you’re going to donate or receive electrons, or release the energy of phosphate cleavage, you don’t need a flat molecule that hydrogen-bonds with another (only when ‘upside down’) and is capable of mutual template specification through that complementarity.

    You wouldn’t do it like that. You’d optimise for the job in hand: a planar base for a neat stereochemical fit, or some other moiety for optimal energetics. It smacks of co-option of preexisting components.

    You mean humans wouldn’t do it like that. We tend to take a more focused approach without regard for the wider consequences.

    We would optimize for the job in hand. In other words we would focus on specific tasks without concern for how our designs would fit in to the the wider world of designed objects or be able to utilized in future situations.

    It’s a bit like designing threaded nuts and bolts. In the beginning they were made to be optimized for specific designs. Designers didn’t feel the need for standardization. Each manufacturer used their own standard.

    In Britain in 1760, J and W Wyatt introduced a factory process for the mass production of screw threads. However, this milestone led to another challenge: each company manufactured its own threads, nuts, and bolts so there was a huge range of different sized screw threads on the market, causing problems for machinery manufacturers.

    Nature works by different rules. It’s as Goethe said, She doesn’t care about individuals. As long as the whole maintains its viability over time, Nature is satisfied. And this means overall cooperation at the expense of individuals, whether that be individual organisms, species, orders or whatever.

    Standardization in the use of basic materials is crucial to the continuation of evolving life.

    Happy hiking. 🙂

  11. Alan Fox:
    Allan Miller: You wouldn’t do it like that. You’d optimise for the job in hand: a planar base for a neat stereochemical fit, or some other moiety for optimal energetics. It smacks of co-option of preexisting components.

    Alan Fox: Designer is just trying to fool us.

    You mean if he was anything like us, your imagined old grey-bearded man in the sky would only do it that way if he was trying to deceive us. But we’re not fooled. We know how it should be done, don’t we. 🙂

  12. Allan Miller:
    ***Drive-by comment alert!***

    (…)
    My money: the fundamental reaction is RNA polymerisation. All the rest is just repurposing what was already there.

    Great post Allan. I understand your argument. I don’t find it compelling, but I understand it. I feel like an alternative interpretation of the same evidence is that the structure and chemistry of the RNA polymer is the product of selection. The reason it lends itself so well to the polymerization and templating reaction is selection has acted on some deeper system of chemistry and RNA is a long-term result of that.

  13. CharlieM,

    None of this addresses my fundamental challenge. You seem perpetually incurious about the puzzles of nature, and just chuck it all back at Goethe. “Oh well, it just doesn’t play by our rules”. Even there: why not? Why do RNA monomers appear in exactly that form throughout energetics? There’s no energetic reason for it.

    There is a deep puzzle here you are just brushing aside.

  14. Rumraket,

    I feel like an alternative interpretation of the same evidence is that the structure and chemistry of the RNA polymer is the product of selection.

    If you mean Darwinian selection, there needs to be a replication process already in place. That demands complementarity – the bases ‘select’ each other. That creates an extra constraint – you can’t fiddle with the hydrogen-bonding of one of a complementary pair without upsetting the other.

    But either way, would you agree that the widespread appearance of RNA bases in cellular energetics would appear to be subsequent to their role in the RNA polymer? You could take any old molecule of ATP, or slice the nucleotides out of any old bit of NAD etc, and they would fit in an RNA helix like a glove – because the bases are planar, and H bond precisely with UTP in antiparallel orientation.

  15. Allan Miller: If you mean Darwinian selection, there needs to be a replication process already in place. That demands complementarity

    I don’t think so. That is one way where it is easy to see how you can achieve Darwinian selection by having structural complementarity as a basis for replication, but replication (or at least, reproduction) itself does not demand direct structural complementarity. There is theoretical work showing that you can get reproduction through other physical mechanisms. See for example this recent work on such a model:
    Attractor dynamics drives self-reproduction
    in protobiological catalytic networks

    Allan Miller:
    But either way, would you agree that the widespread appearance of RNA bases in cellular energetics would appear to be subsequent to their role in the RNA polymer?

    I’m not persuaded of that. It seems to me very much an open question about the timing and role of bases and nucleotide derivatives of all sorts in the earliest stages of chemical evolution.

  16. Rumraket,

    replication (or at least, reproduction) itself does not demand direct structural complementarity. There is theoretical work showing that you can get reproduction through other physical mechanisms.

    Sure, but then you have the hard problem of transition from a mechanism not involving complementarity to one that does. I just don’t see how that would work – serial selection tunes improvements in Mechanism X, then nucleic acid just … kinda … takes over. Presumably badly, at first. Why? How? What benefit could cause the Mechanism X replicator to evolve complementary replication? It can already replicate.

    Allan Miller:
    But either way, would you agree that the widespread appearance of RNA bases in cellular energetics would appear to be subsequent to their role in the RNA polymer?

    Rumraket:
    I’m not persuaded of that. It seems to me very much an open question about the timing and role of bases and nucleotide derivatives of all sorts in the earliest stages of chemical evolution.

    Well, you have me stumped. I can see no reason why ATP, or the adenosine bases in the various cofactors, should have the capacity to H-bond with U, and polymerise 5′-3′ in classical spiral fashion with that complement – in short, to be an actual RNA monomer – if that complementary helical capacity did not come first.

    It’s like finding a glove in a box and insisting it has nothing to do with classical hand-glove interactions, but is instead just one o’those things! A massive coincidence, possibly predating the use of gloves on hands? Nah.

  17. Allan Miller: Sure, but then you have the hard problem of transition from a mechanism not involving complementarity to one that does. I just don’t see how that would work – serial selection tunes improvements in Mechanism X, then nucleic acid just … kinda … takes over. Presumably badly, at first. Why? How? What benefit could cause the Mechanism X replicator to evolve complementary replication? It can already replicate.

    One possibility is genes began as parasites. Literal parasites on some sort of evolving metabolism that was generating nucleotides because they had some other metabolic role.

    And in a similar way to how genetic parasites, or endosymbionts, can begin as parasites, their presence can be coopted to serve useful purposes. So to begin with some sort of evolving metabolic cycle was generating RNA monomers, which had some sort of useful chemical role in this metabolism, but a byproduct was these RNA monomers could link up and generate polymers, of which some eventually functioned as parasites that literally leeched matter and energy from this system to serve their own replication. But because RNA is also able to have a breadth of catalytic roles besides things that directly contribute to their own replication, they could take on functions that aided their hosts and thus indirectly their own surival. They could massively speed up reactions that previously did not benefit from ribozymal accelerations, and suppress others that produced deleterious byproducts, etc. In this way they gradually evolved the ability to accelerate and regulate many of the reactions that were already occurring, while also suppressing others and so reducing waste etc. etc.

    Allan Miller: I can see no reason why ATP, or the adenosine bases in the various cofactors, should have the capacity to H-bond with U, and polymerise 5′-3′ in classical spiral fashion with that complement, if that complementary helical tendency did not come first.

    Ehh that seems confused to me. The actual molecules U and A have the structure they do regardless of whether they first began by having roles in polymerization, or something else (catalysts, reactants in some chemical cycle or whatever).
    So of course their complementarity is intrinsic to their structure regardless of what they’re doing. You can’t separate the complementarity of A and U from the actual molecules so that the molecules can come before their complementarity(as if a hand can emerge without it being complementary to a hypothetical glove), and neither can their complementarity come before the actual molecules. That just makes zero logical sense. Obviously I am suggesting no such thing.

    Neither did I mean to suggest that the monomers of RNA were somehow unable to be complementary, and then their complementarity evolved. Rather the idea is when I suggested RNAs replication ability is a product of selection, that these specific bases were selected out of a host of chemically related molecules of which these were just better at it, exactly because of their high intrinsic complementarity.

    The question is if the very first thing, the very first role that (say) A or U had (and their many precursors and derivatives), was their roles as monomers in RNA polymers, or if they individually served other useful functions before they later got linked together into polymers and thus began to participate in sequence replication. The idea is that there was some sort of chemical system generating nucleotides, and the nucleotides did something in this chemical system before the nucleotides got into polymerization, and this feedstock of nucleotide generation at some point became parasitized by the polymers.

    I just don’t see why we should think the chronological order of functions you suggest, with polymerization coming before the other functions RNA monomers and their various derivatives have (or could have had) is a better explanation for their existence than mine.

  18. Rumraket,

    One possibility is genes began as parasites.

    Doesn’t help you. The fundamental problem in these scenarios is that Mechanism X has an evolutionary history, while complementary pairing does not. So X will be better at it through iteration and selection. In order to get more than one copy of these ‘parasitic genes’, they have to work, as replicators-within-replicators, from the outset***. The existing replicator will be, all else equal, better at it. So how does a feeble replicator take over a good one?

    ***Of course this is true of the very first RNA replicator in other models too, but putting it inside a preexisting cell does not solve that.

    Allan Miller: I can see no reason why ATP, or the adenosine bases in the various cofactors, should have the capacity to H-bond with U, and polymerise 5′-3′ in classical spiral fashion with that complement, if that complementary helical tendency did not come first.

    Rumraket
    Ehh that seems confused to me. The actual molecules U and A have the structure they do regardless of whether they first began by having roles in polymerization, or something else (catalysts, reactants in some chemical cycle or whatever).

    So you’d have the capacity to polymerise and specify the antiparallel complement as incidental? Strong disagree. There are 4 chiral carbons, so 16 different stereoisomers, looking at the ribose.alone. There are vastly more similar structures that wouldn’t work in RNA than would. Many of these would make a perfectly serviceable energy currency or cofactor.

    So of course their complementarity is intrinsic to their structure regardless of what they’re doing.

    It isn’t though! ATP the ‘energy currency’ could have many different structures, many of which will not polymerise 5′-3′ or bind a complement. But It isn’t one of those; it is an actual RNA monomer. One of the vastly many possible near-misses would serve an energetic role just as well or better, shorn of the additional constraint to polymerise 5′-3′, or H-bond to an antiparallel complement.

    Rather the idea is when I suggested RNAs replication ability is a product of selection, that these specific bases were selected out of a host of chemically related molecules of which these were just better at it, exactly because of their high intrinsic complementarity.

    I can buy the idea that there can be an element of selection for base pairs. But that must (surely?) be driven by their role in a double-chained polymer. What is unclear to me is why you think the singleton molecules could have the exact structure required to polymerise and complement before polymerisation and complementarity added these constraints. What use is base pairing or polymerisation to a singleton?

    I just don’t see why we should think the chronological order of functions you suggest, with polymerization coming before the other functions RNA monomers and their various derivatives have (or could have had) is a better explanation for their existence than mine.

    See above?

    There are many more nucleotide variants than will polymerise neatly, or hydrogen bond with a complement. Yet the metabolic variants we use have exactly the right structure to do both. I find that strange, and compelling.

  19. Allan Miller:
    Rumraket,
    Doesn’t help you. The fundamental problem in these scenarios is that Mechanism X has an evolutionary history, while complementary pairing does not. So X will be better at it through iteration and selection. In order to get more than one copy of these ‘parasitic genes’, they have to work, as replicators-within-replicators, from the outset***. The existing replicator will be, all else equal, better at it. So how does a feeble replicator take over a good one?

    It doesn’t take it over, at least initially. It merely comes along for the ride. And it doesn’t strictly have to catalyze it’s own replication, merely inadvertently be replicated through complementary base-pairing.

    What I’m thinking of here is a scenario borrowing some concepts similar to the one proposed in this paper:
    Universal Sequence Replication, Reversible Polymerization and Early Functional Biopolymers: A Model for the Initiation of Prebiotic Sequence Evolution.

    My idea is that of a continuous generation of polymers some of which can be replicated non-enzymatically through complementary base-pairing.

    The point is the polymers are generated as an unavoidable byproduct of some other function the monomer nucleotides have in the host reproducer. And yes there would likely be many dead-end polymers forming that never got off the ground exactly because they did not lend themselves to complementary base-pairing and thus could not get replicated.

    And it actually doesn’t follow at all that the host reproducer is intrinsically superior in speed than non-ribozymal polymerization and replication would be. The relative rates certainly matter, but you’re making an assumption about how good a replicator these first metabolic ensembles could be before enzymes and ribozymes evolved to catalyze their functions. But exactly because they’re not relying on such incredibly effective catalytic rate-accelerators they would probably be orders of magnitude slower than even primitive ribozymes and non-enzymatic template replicators.

    Allan Miller:
    So you’d have the capacity to polymerise and specify the antiparallel complement as incidental? Strong disagree.

    That’d be true on any model for the origin of RNA. Some sort of scenario is posited that just happens to have the properties that it produces molecules that lend themselves to complementary base-pairing and metabolic rules, presumably among a larger ensemble of molecules of which many do not have the properties of being able to replicate through complementary base-pairing. How are you yourself not positing this?

    Allan Miller:
    It isn’t though! ATP the ‘energy currency’ could have many different structures, many of which will not polymerise 5′-3′ or bind a complement. But It isn’t one of those; it is an actual RNA monomer. One of the vastly many possible near-misses would serve an energetic role just as well or better, shorn of the additional constraint to polymerise 5′-3′, or H-bond to an antiparallel complement.

    And those that didn’t polymerize or didn’t bind a complement while serving a role critical to the evolving ensemble eventually were suppressed by those that could generate polymers. I genuinely don’t see how this is a problem for the scenario I’m positing here.

    There is a host of molecules being generated that have various metabolic roles, but only a subset of these are capable of forming polymers that can get replicated through complementary base-pairing. Obviously those that aren’t capable of this do not find a role as monomers in evolving polymers. As evolving polymers evolve cooperative functions in this ensemble, they also eventually act to suppress or discard things that do not contribute to their own replication.

  20. Rumraket,

    It doesn’t take it over, at least initially. It merely comes along for the ride.

    In order to persist it must, in some way, enhance the survival of its host. If so, and its host is a ‘Mechanism X Replicator’, then ISTM that the beneficiary here is Mechanism X – more organisms will exist having Mechanism X+. It doesn’t seem that Mechanism X is on the way out here.

    And it doesn’t strictly have to catalyze it’s own replication, merely inadvertently be replicated through complementary base-pairing.

    I can’t see a use for complementary base pairing in this nonreplicative scenario. OK it can support secondary structure, but it has to replicate, otherwise how do you get more copies of the successful sequences? There are no non-templated mechanisms of chain extension now, and I don’t see a good reason to appeal to them in the past. Sequence begets sequence, ever and ever amen.

    The point is the polymers are generated as an unavoidable byproduct of some other function the monomer nucleotides have in the host reproducer.

    There is no reason here for these proto-monomers to have the capacity to polymerise or base-pair though. They have no constraint in either of those directions. Which leads me, at least, to conclude that those constraints already existed when the monomers were co-opted into energy currency or oxidative energetics. Energy currency/oxidoreduction could have been provided by any old base, in principle, including noncanonical ones. But that isn’t the case. This needs explaining.

    And yes there would likely be many dead-end polymers forming that never got off the ground exactly because they did not lend themselves to complementary base-pairing and thus could not get replicated.

    May as well stick that process outside a cell as inside!

    And it actually doesn’t follow at all that the host reproducer is intrinsically superior in speed than non-ribozymal polymerization and replication would be.

    I’m not really talking about speed. Everything your bare-bones Mechanism X Replicator needs is carried down the generations when it replicates. It presumably specifies itself, and that specification has been tuned by selection. Along comes a ‘gene’ held in RNA that somehow enhances survival of Mechanism X Replicators. It seems highly unlikely that this function cannot be provided by Mechanism X, and still less likely that these early ‘genes’ will replicate/be replicated with any fidelity, initially.

    The relative rates certainly matter, but you’re making an assumption about how good a replicator these first metabolic ensembles could be before enzymes and ribozymes evolved to catalyze their functions.

    This sounds like special pleading! If they persisted, they were perfectly adequate replicators. Of course we do have a scenario in protein coding whereby one mechanism is thought to supplant the other, but that is different from a complete switch of specification.

    Allan Miller:
    So you’d have the capacity to polymerise and specify the antiparallel complement as incidental? Strong disagree.

    Rumraket: That’d be true on any model for the origin of RNA.

    No. I’m not talking about the origin of RNA there, but of the adenosine-containing energetic molecules ATP, NAD etc. It seems an almighty coincidence that these could polymerise 5′-3′, and base pair with U if that requirement had never before existed in their history. A hydroxyl or methyl group here, an atom swap there, and you’ve destroyed H bonding and 5′-3′ polymerisation. Yet (on your view) it’s almost as if these capacities were prespecified in anticipation of a future need.

    Some sort of scenario is posited that just happens to have the properties that it produces molecules that lend themselves to complementary base-pairing and metabolic rules, presumably among a larger ensemble of molecules of which many do not have the properties of being able to replicate through complementary base-pairing. How are you yourself not positing this?

    In context, I’m not arguing about the prior history of RNA from the very beginning. All I’m saying is that, on the evidence, ATP, NAD, FAD, CoA etc are derivatives of monomers that already had a role in RNA.

    Allan Miller:
    It isn’t though! ATP the ‘energy currency’ could have many different structures, many of which will not polymerise 5′-3′ or bind a complement. But It isn’t one of those; it is an actual RNA monomer. One of the vastly many possible near-misses would serve an energetic role just as well or better, shorn of the additional constraint to polymerise 5′-3′, or H-bond to an antiparallel complement.

    Rumraket
    And those that didn’t polymerize or didn’t bind a complement while serving a role critical to the evolving ensemble eventually were suppressed by those that could generate polymers. I genuinely don’t see how this is a problem for the scenario I’m positing here.

    The point of mine you started off objecting to is that I argue the evidence points to ATP/NAD adenosine moieties being already tuned to work in double-stranded RNA polymers – ie, they came after RNA; RNA monomers were co-opted for other roles. In your alternative scenario, ATP etc come first, and just happen to be in a spot-on configuration for polymerisation and base pairing. What luck! 😉

  21. I’m enjoying this exchange and nieces leave tomorrow, so have stickied the OP and encourage folks to read the latest comments and join in even!

  22. Allan Miller: CharlieM,

    None of this addresses my fundamental challenge. You seem perpetually incurious about the puzzles of nature, and just chuck it all back at Goethe. “Oh well, it just doesn’t play by our rules”. Even there: why not? Why do RNA monomers appear in exactly that form throughout energetics? There’s no energetic reason for it.

    There is a deep puzzle here you are just brushing aside.

    And you propose co-option as a possible solution. That implies a build up of extra properties over time. For instance, the molecules involved in energy provision being co-opted from those required for polymerization.

    But there is another possibility. Both functions could have appeared at the same time. So instead of one molecule being co-opted from the other, the original molecules, or molecular complexes, diversified into their respective functions neither of which were prior. Energetics and polymerizations began their relationships by parallel processes and not series processes.

  23. CharlieM,

    And you propose co-option as a possible solution. That implies a build up of extra properties over time. For instance, the molecules involved in energy provision being co-opted from those required for polymerization.

    As far as ATP is concerned, the molecule gains no ‘extra properties’. The ATP we use to power cells IS an RNA monomer, completely indistinguishable. What ‘builds up’ are peripheral processes that utilise this monomer.

    But there is another possibility. Both functions could have appeared at the same time. So instead of one molecule being co-opted from the other, the original molecules, or molecular complexes, diversified into their respective functions neither of which were prior. Energetics and polymerizations began their relationships by parallel processes and not series processes.

    I think this makes too many demands on probability. Adenosine adopts the ‘RNA monomer’ configuration not only as ATP but also in numerous metabolic cofactors: NAD(P), FAD, Coenzyme A, FMN, PAPS, SAM, THF. It is not (apparently) constrained to have this configuration in those other molecules. This leads me to think that configuration is contingent. Simultaneity seems unlikely. If all were ‘designed’ at the same time, I guess that might fly, but that leaves open the question: why do these singleton moieties retain the RNA-monomeric form?

    In conventional evolutionary terms, the answer is likely to be secondary constraint – the systems generating and consuming these molecular species pin their form in place, even though that form is not strictly necessary in all its parts for function.

  24. Allan Miller: CharlieM,

    “CharlieM: And you propose co-option as a possible solution. That implies a build up of extra properties over time. For instance, the molecules involved in energy provision being co-opted from those required for polymerization.”

    Allan Miller: As far as ATP is concerned, the molecule gains no ‘extra properties’. The ATP we use to power cells IS an RNA monomer, completely indistinguishable. What ‘builds up’ are peripheral processes that utilise this monomer.

    “CharlieM: But there is another possibility. Both functions could have appeared at the same time. So instead of one molecule being co-opted from the other, the original molecules, or molecular complexes, diversified into their respective functions neither of which were prior. Energetics and polymerizations began their relationships by parallel processes and not series processes.”

    Allan Miller: I think this makes too many demands on probability. Adenosine adopts the ‘RNA monomer’ configuration not only as ATP but also in numerous metabolic cofactors: NAD(P), FAD, Coenzyme A, FMN, PAPS, SAM, THF. It is not (apparently) constrained to have this configuration in those other molecules. This leads me to think that configuration is contingent. Simultaneity seems unlikely. If all were ‘designed’ at the same time, I guess that might fly, but that leaves open the question: why do these singleton moieties retain the RNA-monomeric form?

    In conventional evolutionary terms, the answer is likely to be secondary constraint – the systems generating and consuming these molecular species pin their form in place, even though that form is not strictly necessary in all its parts for function.

    I bow to your superior knowledge of chemistry.

    As for demands on probability, it depends on what our initial assumptions. In my opinion the probability of life emerging from non-life through chance processes is virtually zero. It’s like the the old tornado in a junkyard scenario. Even if all the components required to build a 747 where present it would never happen. But if the tornado was replaced by a team of Boeing engineers, then the probability would be considerably reduced. Blind processes being replaced by directed processes.

    I can see a fractal pattern in these natural processes. The adenosine involved in energy production does not polymerize to form complex multimolecular chains. By remaining at a less developed earlier stage, this molecule provides the energy for nucleotide polymerization.

    Compare this to evolution at the level of the organism. Prokaryotes do not form complex multicellular organisms. By remaining at a less developed earlier stage, these organisms provide the energy which allows multicellular organisms to evolve.

    It could be said that by remaining at an earlier stage these lower entities lay down the base from which the later entities can grow. No primal entity would be able to be ‘co-opted’ unless it already possessed the properties that gave it the potential to co-operate in these more complex later forms.

    There is untold wisdom in the processes of the being of Nature.

  25. CharlieM,

    In my opinion the probability of life emerging from non-life through chance processes is virtually zero. It’s like the the old tornado in a junkyard scenario. Even if all the components required to build a 747 where present it would never happen. But if the tornado was replaced by a team of Boeing engineers, then the probability would be considerably reduced. Blind processes being replaced by directed processes.

    Oh, that old chestnut. Hang your head in shame for peddling that ludicrous and overworked analogy. Molecular processes are not usefully related to operations at the scale of plane parts, and the forces operating at molecular scales are nothing like tornadoes. It is clearly a persuasive slice of nonsense, since one sees it repeatedly, but nonsense it remains.

    I am not, in any case, talking of the origins of life.

  26. CharlieM,

    It could be said that by remaining at an earlier stage these lower entities lay down the base from which the later entities can grow. No primal entity would be able to be ‘co-opted’ unless it already possessed the properties that gave it the potential to co-operate in these more complex later forms.

    Which are the primal entities and which the later forms in this scenario?

    There is untold wisdom in the processes of the being of Nature.

    Well, that’s cleared that one up!

  27. Allan Miller,

    Oh, that old chestnut.

    I just spent 20 minutes throwing screws at a piece of chipboard. Not one of them screwed itself in. Then I threw a bit of sodium at some chlorine. Again, futile.

    But I did at least demonstrate, by analogy, that both Design and chemistry are impossible.

  28. Allan Miller: CharlieM,

    “CharlieM: In my opinion the probability of life emerging from non-life through chance processes is virtually zero. It’s like the the old tornado in a junkyard scenario. Even if all the components required to build a 747 where present it would never happen. But if the tornado was replaced by a team of Boeing engineers, then the probability would be considerably reduced. Blind processes being replaced by directed processes.”

    Allan Miller: Oh, that old chestnut. Hang your head in shame for peddling that ludicrous and overworked analogy. Molecular processes are not usefully related to operations at the scale of plane parts, and the forces operating at molecular scales are nothing like tornadoes. It is clearly a persuasive slice of nonsense, since one sees it repeatedly, but nonsense it remains.

    I am not, in any case, talking of the origins of life.

    You are jumping to conclusions about the point I am trying to make. I am not equating a tornado in a junkyard with the contemporary theories of evolution. I was giving that scenario as an example of something that would be so improbable as to be equivalent to zero. A team of engineers with all the available equipment would have a probability closer to one. Life evolving by the means envisioned by contemporary evolutionists would have a probability higher than the tornado scenario, but still have a very low probability.

    I had proposed a possible scenario and you countered that it wasn’t feasible because of the ‘demands on probability’. But these demands only apply if contemporary evolutionary theories hold good and evolution is indeed blind. Alternative theories will change the probability of occurrences.

    Probabilities will vary depending on whether evolution has goals or whether it is blind. And so I was making the point that this blunts your point. 🙂

  29. Allan Miller: CharlieM,

    “CharlieM: It could be said that by remaining at an earlier stage these lower entities lay down the base from which the later entities can grow. No primal entity would be able to be ‘co-opted’ unless it already possessed the properties that gave it the potential to co-operate in these more complex later forms.”

    Which are the primal entities and which the later forms in this scenario?

    Primal entities are organisms that live their lives as single cells. Later forms are those that through their complex, multicellular existence they are able to have some measure of conscious control over their actions. They make decisions about how they interact with the world around them.

    Evolution and individual development can be thought of as similar processes on different levels. The whole reflected in the parts. My primal form as an individual was as a single cell wholly dependent on the environment to which it belonged. I subsequently developed into a much more liberated multi-cellular being with the ability to make independent decisions.

    I believe that single-celled organisms were the first to appear on this earth as individual physical creatures. And through evolution the range of creatures now present can be seen to populate the earth. This evolution has reached a stage in which life is able to look back on itself and acknowledge its own existence.

  30. Allan Miller:
    Allan Miller: Oh, that old chestnut.

    I just spent 20 minutes throwing screws at a piece of chipboard. Not one of them screwed itself in. Then I threw a bit of sodium at some chlorine. Again, futile.

    But I did at least demonstrate, by analogy, that both Design and chemistry are impossible.

    My advice would be to take a moment instead of immediately rushing into pointless activity. Sit down and contemplate one of the screws. Study its form, enquire as to its history, how it came to be and why was it shaped the way it was. Does it have a function? What relationship could it have with other objects? Why and how did it come to be made from a specific material? Examine the screw in detail and it might just reveal the secrets of its design.

    Also, I have a question, if you don’t mind answering: how did you obtain the isolated substances of sodium and chlorine? 🙂

  31. CharlieM,

    Primal entities are organisms that live their lives as single cells.

    I am talking about the RNA moieties.

  32. CharlieM,

    I was mirroring the ‘tornado’ scenario, in jest. It is an over-elaborate, and hackneyed, way of making a point. Reality is that even a single screw will not approach its target with the torque necessary, regardless whether through accident or design. But it demonstrates nothing, since chemistry is not mechanics.

  33. CharlieM,

    Examine the screw in detail and it might just reveal the secrets of its design.

    I did. That’s why I was chucking it at the wood! It’s clearly meant to embed itself in some way. But buggered if I could design my way outta that one.

    And how do I apply this principle to atoms?

  34. Allan Miller: In order to persist it must, in some way, enhance the survival of its host.

    No. Spandrels are a thing. So is parasitism, and a host of other phenomena where one sort of organism persists on another.

    Allan Miller:
    I think you are onto a loser if you are invoking neutral processes!

    That isn’t an argument at all, and neutral processes are an unavoidable reality in evolution.

    Allan Miller:
    If so, and its host is a ‘Mechanism X Replicator’, then ISTM that the beneficiary here is Mechanism X – more organisms will exist having Mechanism X+. It doesn’t seem that Mechanism X is on the way out here.

    These are just assumptions you are making with no justification.

    Allan Miller:
    I can’t see a use for complementary base pairing in this nonreplicative scenario.

    I was distinguishing replication by self-catalyzation(say a ribozyme that can catalyze it’s own polymerization from a template) from replication by something else (in both cases templated replication through complementary base-pairing), not trying to say there was replication without templating.

    Allan Miller:
    There are no non-templated mechanisms of chain extension now, and I don’t see a good reason to appeal to them in the past. Sequence begets sequence, ever and ever amen.

    Allan on your own view the first sequence would have to be the literal first sequence that didn’t emerge from being templated on a prior polymer sequence. Your very own view logically requires the first polymer to assemble through some sort of chain-extension mechanism without a prior template. Either just randomly in solvent, or on some mineral surface or whatever. This is just logically and physically unassailable. However the first polymer arose, it can’t have been by extension on a complementary polymer (which would then have to have been the first.) No way out of this.

    Allan Miller:
    There is no reason here for these proto-monomers to have the capacity to polymerise or base-pair though.

    I am astonished by this extreme hyperadaptationist reasoning where molecules need “reasons” for having properties that are conducive to later evolutionary developments.

    Exaptation is a thing.

    As if the fact that some amino acid in a protein that presumably has a function now, today, in my brain, needs to have a reason for having this property that is conducive to it’s function in my brain 4 billion years later. This property can be entirely incidental and secondary, or a spandrel to what it first was doing. Things don’t have to have reasons to have properties that will later turn out to be conducive to other functions they take on.

    There are structural proteins that evolved from enzymes because the active site of the enzyme happened to have a binding interface structurally complementary to a binding partner that evolved millions of years after the enzyme first emerged. Things really do just happen to have properties that will later turn out to be adaptive in other circumstances.

    Feathers first evolved for thermal insulation, and turned out eventually to be useful for flight.

    Allan Miller:
    They have no constraint in either of those directions. Which leads me, at least, to conclude that those constraints already existed when the monomers were co-opted into energy currency or oxidative energetics. Energy currency/oxidoreduction could have been provided by any old base, in principle, including noncanonical ones. But that isn’t the case. This needs explaining.

    Any of a host of explanations for why X can be provided in principle. The extant ones could have been better at it, more easily synthesized (and thus more abundant) or whatever. I’m not required to actually explain why X instead of Y to show that your initial hypothesis that their extant functions are chronologically later to template replication is not necessary nor implied by their co-occurrence with their functions in templated replication.

    Allan Miller:
    May as well stick that process outside a cell as inside!

    I don’t understand in what way this is a response to the part you quoted in my post.

    Allan Miller:
    I’m not really talking about speed. Everything your bare-bones Mechanism X Replicator needs is carried down the generations when it replicates. It presumably specifies itself, and that specification has been tuned by selection. Along comes a ‘gene’ held in RNA that somehow enhances survival of Mechanism X Replicators. It seems highly unlikely that this function cannot be provided by Mechanism X

    Why? This reasoning makes absolutely zero logical sense. The fact that a reproducer has been the subject of prior generations of selection doesn’t mean some novel molecule can’t provide a survival advantage (though this also isn’t strictly required to explain why a novel molecule can persist along with a reproducer, for reasons already well known in evolutionary biology: spandrels, parasitism, etc.)

    Allan Miller:
    and still less likely that these early ‘genes’ will replicate/be replicated with any fidelity, initially.

    Initially, yes. At that stage there must have operated some sort of universal sequence replication (see earlier reference). This same fact is required on your own theory. Polymers must have begun before they could self-replicate(it is very unlikely that the very first non-templated polymer(which there would logically have to have been) would just happen to also be a self-replicator. So a priori it is more likely that some sort of low-fidelity templating replication must have occurred over long time scales, and from this sequence-exploration sequences that could aid and bias their own replication over and above others must have been selected out.

    Allan Miller:
    This sounds like special pleading! If they persisted, they were perfectly adequate replicators.

    You have to do the same thing. The first RNA replicator must have had conditions necessary to survive, and the environment must have had properties that were not too stringent to destroy it, etc.

    Sorry I just don’t see why I have to assume that this is any sort of obstacle to my hypothesis any more than anyone else does.

    All theories for the origin of life must involve some sort of special pleading where anything from environmental circumstances to the chance occurrence of certain polymers with useful functions in large pools of sequences would have had to emerge.

    Heck, even on creationism it’s special pleading. There must have been this magical dude who totally could just wish things with the right properties into existence because otherwise there can’t be life now. We all have to do this at some point to explain our existence. The circumstances must have been right to get the right thing with the right properties to get to here from there. This isn’t a point for or against anyone in this discussion.

    Allan Miller:
    Of course we do have a scenario in protein coding whereby one mechanism is thought to supplant the other, but that is different from a complete switch of specification.

    You call it a complete switch of specification, but I’d call it an addition. There wasn’t a prior polymer that got supplanted on my view. Rather, things were added to the system that improved it, and the system later got dependent on it. Like so much else in evolution it’s a ratchet. To begin with they were probably just spandrels, then they became beneficial, and finally they became essential.

    At some point in the past there were no organisms with beating hearts. You take mine out I die, it is absolutely critical to my life. And yet I have ancestors who lived, grew, and reproduced without a heart. And they had circulatory systems still. The beating heart evolved from some more primitive musculature that produced movement of fluids in this system, and that in turn evolved from an even more primitive passive diffusion system. Technically if you took out my heart there would still be some degree of passive diffusion in my veins at least for a short time, but this rate just wouldn’t be enough to sustain all the functions of my body. In this way the heart didn’t so much supplant the previous systems as it merely added to them in a way that allowed other things to build on top.

    Allan Miller:
    No. I’m not talking about the origin of RNA there, but of the adenosine-containing energetic molecules ATP, NAD etc. It seems an almighty coincidence that these could polymerise 5′-3′, and base pair with U if that requirement had never before existed in their history. A hydroxyl or methyl group here, an atom swap there, and you’ve destroyed H bonding and 5′-3′ polymerisation. Yet (on your view) it’s almost as if these capacities were prespecified in anticipation of a future need.

    How do you get polymers of RNA without first having synthesized monomers like ATP and UTP? On your own view there would just happen to be some nonbiological chemical pathways for the synthesis of monomers, which then by sheer luck could link up into polymers, and then could base-pair in complementary fashion. What remarkable luck that the environment produced molecules with these properties.

    Clearly your own theory would suffer from this problem. You can’t avoid it.

    Allan Miller:
    In context, I’m not arguing about the prior history of RNA from the very beginning. All I’m saying is that, on the evidence, ATP, NAD, FAD, CoA etc are derivatives of monomers that already had a role in RNA.

    I understand what your view is, I’m just disputing that this is what the evidence shows. And this same evidence can just as easily be explained by the hypothesis that the derivatives and precursors of the monomers of RNA had functional chemical roles in some sort of evolving metabolism before the first polymers evolved.

    I’m not the first guy suggesting things like NAD+/NADH, ATP or what have you, could have had functional roles in metabolism prior to RNA-based cells:
    Role of geochemical protoenzymes (geozymes) in primordial metabolism: specific abiotic hydride transfer by metals to the biological redox cofactor NAD+

    Incidentally, I’m also not the first guy to suggest the scenario where RNA emerged in some sort of metabolic system that could reproduce without having any genes:
    Coevolution of reproducers and replicators at the origin of life and the conditions for the origin of genomes

  35. Rumraket,

    Allan Miller: In order to persist it must, in some way, enhance the survival of its host.

    Rumraket: No. Spandrels are a thing. So is parasitism, and a host of other phenomena where one sort of organism persists on another

    Allan Miller:
    I think you are onto a loser if you are invoking neutral processes!

    Rumraket: That isn’t an argument at all, and neutral processes are an unavoidable reality in evolution.

    The existence of these things does not justify their invocation in a particular scenario. Would you see protein coding as likely neutral? If so, where are all the non protein coders? Similar reasoning applies.

  36. Allan Miller: The existence of these things does not justify their invocation in a particular scenario.

    I don’t understand what you’re saying here.

    Allan Miller: Would you see protein coding as likely neutral?

    No. Why would I? That some things could be neutral(not that it has to be neutral) does not mean everything has to be, or begin, neutral.

    And of course, even things that are conditionally deleterious can still persist because they are a byproduct of some other stronger adaptation. Suppose that The reaction of molecule D -> E produces a small amount of K as a byproduct. Suppose E is strongly beneficial to the organism, but K is weakly deleterious. K could be parasitizing polymers that are unavoidably the result of the strongly beneficial reaction D -> E. And there’s just no way to get E without the small amount of K byproduct. Then K sticks around parasitizing on the organism, because E is just so beneficial it’s worth doing even though we get a bit of K.

    But K, the polymers, can evolve new functions. They can evolve functions that are beneficial to their host, such as suppressing side reactions that produce other forms of waste (other essential reactions R -> O produce wasteful side-product I that can’t be gotten rid of until polymers of K happen on that function by chance.)

    The possibilities here are basically endless, and there’s just no conceptual difficulty with the idea that something can begin and come along for the ride as a sort of parasite, or spandrel, or what have you.

  37. Rumraket,

    I’m not the first guy….

    These are all just arguments from authority. I’m not the first guy to point out the surprising monomeric form adenosine takes in these other molecules either, where the monomeric form is not apparently necessary for function. But these people are not here to interrrogate on that aspect, so it’s just argument by glove puppet.

    Anybody offering a temporal sequence where these metabolic molecules came first, I’d like to know why they have a polymerisable form with an edge hydrogen-bondable with antiparallel U, when many other structures lacking that would work. These features are not necessary for function.

  38. Rumraket,

    No. Why would I?

    Well, same goes for me. I don’t see the complete replacement of a prior mechanism of replication and specification as a viable candidate for a neutral change.

  39. Rumraket,

    I don’t understand what you’re saying here.

    You just said ‘spandrels are real, parasitism, neutral drift…’. There has to be a reason to invoke one or the other, beyond giving me a lesson in evolutionary concepts.

  40. Rumraket,

    You have to do the same thing. The first RNA replicator must have had conditions necessary to survive, and the environment must have had properties that were not too stringent to destroy it, etc.

    The constraints on a competent replicator to evolve a completely different way of replication and specification are evidently different from those on the very first replicator. There are all these competitors…

  41. Rumraket,

    The fact that a reproducer has been the subject of prior generations of selection doesn’t mean some novel molecule can’t provide a survival advantage

    But this novel molecule ought to be within the capacity of Mechanism X to furnish. Oughtn’t it?

    We have an unlikely scenario where a novel molecule would give an advantage but NO WAY can Mechanism X do it! “Leave it to me”, says RNA, which can magically also replicate that capacity so it spreads…

  42. Rumraket,

    And this same evidence can just as easily be explained by the hypothesis that the derivatives and precursors of the monomers of RNA had functional chemical roles in some sort of evolving metabolism before the first polymers evolved.

    This does not, to labour the point, cut it. I can buy that RNA monomer-like molecules could have had a role. But these are actual RNA monomers. If one invokes exaptation, the likeliest route is RNA->metabolic derivatives. The situations are not symmetrical.

  43. Rumraket,

    How do you get polymers of RNA without first having synthesized monomers like ATP and UTP? On your own view there would just happen to be some nonbiological chemical pathways for the synthesis of monomers, which then by sheer luck could link up into polymers, and then could base-pair in complementary fashion. What remarkable luck that the environment produced molecules with these properties.

    There, we may plausibly invoke a process of chemical selection. All possible monomers are produced, but only some, those with a complement, are stable. Biosynthesis does not have that latitude.

  44. Rumraket,

    I am astonished by this extreme hyperadaptationist reasoning where molecules need “reasons” for having properties that are conducive to later evolutionary developments.

    I’m astonished at this judgemental culture-wars stuff! Yes, I think our ATP and other metabolic forms are the polymerisable form for a reason. Shoot me.

    Exaptation is a thing.

    As if the fact that some amino acid in a protein that presumably has a function now, today, in my brain, needs to have a reason for having this property that is conducive to it’s function in my brain 4 billion years later.

    Free amino acid function would be a good example of what I’m talking about. Wanna bet any functional non peptide free amino acids are the L form, alpha-amino, and would work fine in a ribosomal system? I’d argue they were exapted from protein aa’s. Is that unreasonable?

  45. Anyhoo… I’m back on trail shortly, so can’t pursue this. The last few responses were bitty, as I was fitting them in between visiting the Bristlecone Pines on White Mountain, and going in and out of service on Hwy 395. Then we got a flat in a rainstorm, and there’s no spare, and the car has now locked itself so I can’t get at my stuff, so… Getting towed shortly. As I said, very much a drive-by!

  46. Allan Miller: We have an unlikely scenario where a novel molecule would give an advantage but NO WAY can Mechanism X do it! “Leave it to me”, says RNA, which can magically also replicate that capacity so it spreads…

    Yes. Allan this has to do with pre-genetic chemistry and physics and how it compares to chemistry catalyzed by polymers like ribozymes. It is already well known that many of the chemical reactions catalyzed by enzymes also occur spontaneously but at much slower rates. These same spontaneous chemical reactions also have all sorts of side-products, such as different diastereomers and enantiomers that enzymes and ribozymes discriminate against.

    We can see how such reactions occurring in some primitive replicative ensemble could massively benefit from the spontaneous occurrence of replicative entities that can accelerate favorable reactions, and/or suppressing others (like ribozymes, or even just polymeric chelators that block off certain functional groups on their substrates.)

    As I see it, it is perfectly obvious why the emergence of functional genes would provide the potential for massive advantages in terms of reaction rates and discrimination against wasteful side-reactions that chemistry not accelerated or aided by polymers is very unlikely to be able to accomplish. It’s what enzymes and ribozymes do today that make them so useful.

    The whole idea here is that primordial life was generally just worse at most of the things extant life does. Slower, more noisy, more wasteful, and the initial side-products of some of their internal reactions was polymers of certain molecules, some of which had the ability to base-pair and be replicated.

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