Raw materials for life

If it doesn’t have any other systems to compete with, yes.

Are you not aware that catalysis only speeds up reactions that are going to happen anyway?

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You have introduced a word not used in your quote: efficiency. Carter is speaking about how fine the gradations of control over molecular chemistry is, not the efficiency. Efficiency is about waste in energy or resource pr. unit of work. Finer control means the chemistry can be adjusted by smaller increments. The fact that proteins CAN be fine-tuned to catalyze chemistry in much smaller increments than can ribozymes does not in the least imply ribozymes aren’t sufficiently competent catalysts to power reactions critical to cellular life.
Of course, given that ribozymes do in fact perform essential roles even in life as we know it, that seems to support the inference that ribozymes are sufficiently competent catalysts for life.

Another factor to consider is that ribozymes, like proteins, can use co-factors(coenzymes) to expand their structural and chemical repertoire. Metal ions/mineral clusters, covalently bound amino acids and so on. Ironically some protein enzymes use nucleotides and derivatives as coenzymes.

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Finer control of chemistry results in higher efficiencies seen in some enzymatic reactions. This is explained very well in a paper entitled, “Chiral molecules and the electron spin”. The author explains:

Because of its spin, the electron has a magnetic moment and a magnetic field is usually required to separate (or split) the energies of its two possible spin states (quantum numbers of 1⁄2 or -1⁄2). This splitting energy is typically small and comparable to ambient thermal energies (~0.025 eV). In contrast, the stabilization energy obtained when two electrons of opposite spin occupy the same volume can be large, on the order of 1 eV (~100 kJ/mole); and it arises from the exchange–correlation energy, not the magnetic interactions. A known manifestation of this phenomenon is the energy gap between singlet and triplet states, in which the spins are antiparallel for the singlet and parallel for the triplet.

Given the substantial exchange energy differences associated with the relative spin alignment of electrons, one might expect that it would prove useful for controlling chemical reactions. However, other than photochemical2,3 and some enzymatic4 reactions, spin selection rules are not typically used for improving the selectivity of chemical reactions. The reason is that the spin direction of an unpaired electron in a molecule is often not fixed relative to the bonds of the molecule; it is not defined in the molecular frame. Typically, when one relates to spin states in a molecule (singlet or triplet for example) the states are defined as the orientation of spins of two electrons relative to each other and not relative to the molecular frame. If one applies an external magnetic field, one can relate the spin direction relative to this external magnetic field; however, even then, the spin direction is not fixed with respect to the molecular frame.

So this principle of choral induced spin selectivity, is a mechanism used in cells to bias the correct chemical reactions by reducing the amount of energy required for the appropriate chemical reactions to a tiny fraction of what it would take to initiate the wrong reaction.

So if we imagine a cell without enzymes we are also required to imagine a cell without the above stated advantages. Such a cell would not only be unable to control when and for what duration the reactions needed for it to exist occur, it would also require much more energy to make those reactions both begin and stop them when it needs them to stop. Stated simply it would would be much less efficient in using the energy available to it ,because of wasting much of the energy that it has on side reactions that at best don’t help it survive but more likely actively work against its ability to survive, while simultaneously actively consuming the available reagents that it needs to even exist at all.

Nowhere does that say that RNA ribozymes have insufficient control over chemical reactions to power cellular function. You’re just bluffing with technical text here.

Are we though?

If you’re just going to make stuff up we might as well stop having this discussion entirely. Nothing in any of the papers you have referenced supports these conclusions. You are literally just making all that up.

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Nothing in any of the papers you have referenced supports these conclusions. You are literally just making all that up.

This is at best an extremely unfair and untrue statement. First I need to review what it is that I have actually said.

“Stated simply it would would be much less efficient in using the energy available to it ,because of wasting much of the energy that it has on side reactions that at best don’t help it survive but more likely actively work against its ability to survive, while simultaneously actively consuming the available reagents that it needs to even exist at all.”

Which part of this conclusion is unjustified the fact that ribozymes are less efficient than enzymes? In a paper entitled “The RNA world hypothesis: the worst theory of the early evolution of life (except for all the others)” the author notes:

The majority of naturally occurring ribozymes catalyze phosphoryl transfer reactions – the making and breaking of RNA phosphodiester bonds [51]. Although the most efficient of these ribozymes catalyze the reaction at a comparable rate to protein enzymes – and in vitro selection has isolated ribozymes with a far wider range of catalytic abilities [9,51] – the estimate of proteins being one million times fitter than RNA as catalysts seems reasonable, presumably due to proteins being composed of 22 chemically rather different amino acids as opposed to the 4 very similar nucleotides of RNA [12].

So it is safe to say that they are very inefficient, so I am obviously not making that up. This probably is why ribozymes are only used to catalyze some reactions in the cell, while protein enzymes can catalyze most of the reactions that happen in a cell, with the notable exceptions of the ribosome and the spliceosome, but even in these two cases these ribozymes need proteins to self assemble and function. So neither of these highly functional ribozymes would actually exist in an hypothetical RNA world, instead something like the artificial ribozymes which have yet to independently reproduce and which present no evidence of being able to control cellular respiration much less build it.

Then there is the problem of energy cells actually need energy to function and in real cells DNA encoded protein enzymes convert generalized energy from the environment into specific work. Naturally occurring ribozymes surely do no such thing so how did it work in primordial RNA world cells? Is it logical to assume that those reaction would no tcreate a wide variety of products and since RNA is unstable (think about the shipping requirements of the vaccine) many of those products would be able to destabilize it? I don’t think so, but if you claim that such a conclusion is baseless I would sure like to understand what evidence you are basing that on.
Chiral based spin selectivity is a real process that has not been integrated into origin of life speculations, I think it will hurt them but I realize that you may have never even heard about it so if you like here’s a video made by James Tour on the subject:

I have shared my thoughts about why the purely speculative RNA world cells likely would not function sorry that upsets you. I also feel obliged to point out that all OOL speculations are actually the product of someone just making something up and are most likely incorrect.

That ribozymes are “wasting much of the energy that it has on side reactions”. There’s just no evidence that this is occurring to (and this is the critical point to your claim) such an extend that “at best don’t help it survive but more likely work against its ability to survive, while simultaneously actively consuming the available reagents that it needs to even exist at all”.

These claims are completely unsupported. You simply made it up.

Arguing that ribozymes are inferior catalysts to proteins(which they do seem to be) does not support the conclusion that ribozymes are incapable of supporting some sort of RNA based living system, particularly when there is no reason to suppose that at any stage a plausible prebiotic system would be composed of nothing but RNA alone, but could include metal ions, mineral clusters, and small peptides and other organic cofactors and coenzymes. Like both proteins do today. Heck, proteins even use nucleotides as coenzymes in some reaction. Which also provides a good explanation for why ribozymes are usually supported by RNA-binding proteins.

Of course, nobody is saying that the first cells, or proto-cells, or whatever reproducing chemical systems might have preceded these, would have fitness comparable to extant life. All that just seems to provide a good reason for why selection would favor protein enzymes over ribozymes, evolve bigger peptides and eventually proteins to stabilize and assist ribozymes, and why first life would be outcompeted by it’s descendants and go extinct. And why, if life somewhere still does occasionally originate on the Earth, it would be quickly exterminated once it makes contact with any extant lifeform.

Unfortunately it’s not clear from that quote in what sense the molecule is supposed to be “fitter”(and the paper referenced is behind a paywall). So while there are no doubt many good reasons to think proteins make for superior catalysts to RNA, there’s still no actual support given for your statement that ribozymes are “wasting much of the energy that it has on side reactions” to such an extend(if at all) that “at best don’t help it survive but more likely work against its ability to survive, while simultaneously actively consuming the available reagents that it needs to even exist at all”.

The ribozymes we find in life don’t seem to exhibit these properties, nor do any of the ones isolated by in-vitro selection methods. It should also be noted here that most protein enzymes performing core roles in metabolism and biosynthesis have now been under selection for about 4 billion years, while most in-vitro selected ribozymes undergo somewhere between 10 and 20 rounds of mutagenic PCR and artificial selection, and that in-vitro selected ribozymes are usually selected exclusively for their ability to catalyze a particular reaction of interest to the researcher, with little to no care for how this ability might be tied to the ribozyme’s own survival, whereas the protein enzymes that evolve in living organisms are intrinsically under selection to not somehow work against themselves.

Then there’s the fact that many protein enzymes are wildly promiscous too, catalyzing multiple chemical reactions simultaneously, many of which are “useless” side reactions, and yet the cells in which these exist still do just fine.
Taking more cues from extant life, to some it is even an advantage, as the “side reactions” often times aren’t useless(some enzymes that break down sugars, for example, are rather unselective and work on a whole range of related products).

Having one gene able to perform multiple functions can both favor adaptation to a new niche if the products of the “useless” side reaction becomes beneficial, and it saves genome size (particularly important in viruses). On that latter note, any presumed promiscuity of ribozyme catalysts can actually increase the plausibility of RNA based life, as shorter total genome size alleviates some of the fidelity requirements, metabolic cost of replication, while the promiscuity assists the adaptive potential of an RNA based evolving system (less blind sampling of sequence space is required to find useful new reaction chemistries if the catalysts can already do them). All of these are principles of biochemistry and evolutionary adaptation seen in actual living organisms, which for all the same reasons would also apply to any RNA-based life form.

Sorry but, yes you are. You have not brought any material that supports the inference that ribozyme catalysts are less efficient (“very inefficient”) in a way where they somehow mysteriously eat up available environmental energy on useless side reactions such that it prevents their own survival. It seems to be something you’ve sort of read into a curious selection of quotes that speak more broadly about things like “chemical control” and “fitness”. Are protein enzymes superior catalysts to RNA ribozymes? Sure. Does this imply the conclusion that a largely ribozyme-based lifeform couldn’t function and survive? Nope.

Sorry but you’re not providing any actual explanation for why it should happen to be that RNA is somehow a superior catalyst for these reactions. All you say is these are “notable exceptions”. But why?

Shouldn’t all the reasons you’ve mentioned previously also apply to the catalysis of peptide bond formation, or phosphodiester bond cleavage? There does not seem to be any intrinsic reason why protein enzymes would not also constitute superior catalysts of these reactions, and hence you’ve not actually offered any evidence-based reasons why they are catalyzed by RNA.

By the way, the ribosome has three functions it performs during translation. It catalyzes peptide bond formation. It shuttles tRNA between the small and large ribosomal subunits, and translocates mRNA.
RNA performs all these roles in the ribosome, the proteins do not. The proteins aid assembly, and folding, and through that catalysis, but perform none of the actual functions. Of course the proteins being required now for the function of the ribosome through their roles in assisting assembly and folding, does not imply they always were. That’s like saying worm-like forms of life are impossible ancestors to humans because if you cut off my arms and legs(worms have neither) I die, as if this somehow disproves worms or worm-ancestry. Humans evolved from worms that live just fine without arms and legs. A key to understanding evolution (and can give useful hints about early life and it’s origins) is the realization that [how things are now] =/= [how they always were].

The RNA world hypothesis provides an explanation why the RNA-based functions in extant life even exist, where your rationalization does not. You seem to have tried to provide nothing but reasons that undermine why RNA should be performing any catalytic roles in life at all, making the RNA world hypothesis an all the more compelling explanation: RNA is today performing these roles because by the time fully fledged coded protein biosynthesis had evolved, the process of their biosynthesis had become completely dependent on these RNA-based systems, and hence could no longer be replaced, leaving all subsequent life with this evidence of their ancestry.

Unfortunately none of these assertions follow from the material you have climbed to try to grasp towards these conclusions, but I also now have to wonder why the RNA world is required to perform respiration, as opposed to respiration, or more ancient metabolic processes being a product of inorganically catalyzed metabolic reactions?
But all that has to do more with at what stage life became “free living” cells that could perform all the roles necessary for their own survival and reproduction, as opposed to relying on various environmental processes and cycles to favor particular behaviors. Which we can be sure you know next to nothing about anyway, since nobody does, so these are all open questions.

It has, however, been shown that a naked ribosomal core ribozyme is capable of catalyzing peptide bond formation without the assistance of any proteins:

Also of note is the fact that, also unexplained by you, the ribosomal core (the one responsible for catalysis) appears to have internal symmetry, that is, be derived from a duplication of of two small RNA sequences. Again a fact that the RNA world hypothesis and it’s own evolutionary origin from even smaller RNA-molecules, explains.

Why? Surely they did! Look, argument from mere assertion is easy.

What reactions and what products? You can’t just make up scenarios in your head and then pretend they’re real barriers to the RNA world. So what ribozyme in particular is performing what reactions, what side-products is it producing, and in what way do they inhibit it’s own function or stability?

Would they? You end with a question mark, implying you don’t know. I concur, you do not.

The evidence for the baselessness of your conclusion is the actual absence for it’s basis.

Cool.

Here’s a paper for you. Funny coincidence:

Abstract

The emergence of functional interactions between nucleic acids and polypeptides was a key transition in the origin of life and remains at the heart of all biology. However, how and why simple non-coded peptides could have become critical for RNA function is unclear. Here we show that putative ancient peptide segments from the cores of both ribosomal subunits, as well as derived homopolymeric peptides comprising lysine or the non-proteinogenic lysine analogues ornithine or diaminobutyric acid, potently enhance RNA polymerase ribozyme (RPR) function irrespective of chirality or chiral purity. Lysine decapeptides enhance RPR function by promoting holoenzyme assembly through primer-template docking, accelerate RPR evolution and enable RPR-catalyzed RNA synthesis at near physiological (≥1 mM) Mg2+ concentrations enabling templated RNA synthesis within membranous protocells. Our results outline how compositionally simple, mixed chirality peptides may have augmented the functional potential of early RNAs and promoted the emergence of the first protocells.

We sought to dissect the chemical basis of this RPR activation by varying peptide side-chains and stereochemistry. To our surprise, peptide chirality had little influence upon enhancement, with poly-l-Lysine (ca. K700-K1500) and diastereomeric poly-d-Lysine both boosting Z activity to a comparable extent (Supplementary Fig. 4).

Unfortunately I think if there’s one main problem with all your thinking on this subject, it’s ironically a bit like many of the criticisms that have traditionally been leveled at RNA world proponents. You take the RNA world hypothesis to imply a much purer RNA-only system with RNA being basically responsible for everything that occurs in modern cells. A sort of cell with a lipid bilayer membrane, with all the things found in extant life inside it, except it’s all being made by and constituted for RNA.

It is more plausible that prebiotic chemistry would have been dirtier and produced both RNA and peptides, and that these would have co-existed already from the beginning in a mutually beneficial relationship enhancing both each others’ stability, chemical repertoire, and replicative properties:

LOL. James Tour can’t figure out how or why X, because of [insert technical-sounding reason]. Good for him, but unfortunately what James Tour continues to be unable to figure out how could work is evidence of nothing other than the extend of James Tour’s personal ignorance and continuing unwillingness to try to solve the question.

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What is your measure of efficiency?

Life causes increase in entropy of a system to occur faster. So, in an conservation of energy sense, life is more “inefficient” than non-life.

If you are talking about metabolic speed, well-

Does an organism A, which for argument’s sake, catalyses the exact same reactions as another organism B at a rate 10x, or even 1000000x slower, would A still be life?

Once you define your terms and measurements, your arguments clearly hold no water.

If there was life which catalysed today’s life reactions but 1000000x slower, it would still be life.

Keep in mind enzymes do not catalyse reactions that cannot occur without them - they just increase the rate of already spontaneous reactions. That is why they are called catalysts.

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I would say the process by which the first life-formed appeared is more complex than any human can ever imagine. How is it possible to imagine a process that is scientifically impossible?

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I am in awe. Is there a contest for these things? I will nominate you.

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What any particular person can imagine is highly subjective. In my own profession I often work with high-dimensional data. I don’t need to imagine 50+ dimensions, I have the tools to write it down mathematically -no science fiction involved.

Even with little knowledge of biochemistry, different application show that energy driven chemical reactions have exponentially increasing probability to create something with an essential quality of life (energy dissipation). Here I can only imagine the biochemistry required, but the probability of this happening is no problem; given sufficient energy something like life will happen.

Of course there is a huge difference between demonstrating energy dissipation and the plausibility of OOL occurring due to unguided chemical processes on an early earth.

Sorry for the long delay in responding to your points. I’ve linked an article written by both Brian Miller and Jeremy England that addresses some of the problem of a hypothetical primordial biology that predated enzymes. In it Miller explains in part:

Blockquote Enzymes are essential for energetically favorable reactions since most reactions are too slow to drive cellular operations. Enzymes accelerate the reactions’ turnover rates by factors typically between 108 and 1010, and the increase in many cases is significantly higher.59 Without enzymes, the concentration of a substrate would typically need to be millions of times greater to maintain a comparable reaction rate.

Of course while the hypothetical primordial cell is waiting for the reactions it needs to sustain its life to occur, nothing would be preventing the chemical processes that would cause its death. Which is why I agree with Miller that an enzyme free biology isn’t a realistic scenario. Of course an actual example of a cell that doesn’t need enzymes to exist would demonstrate that my position is unfounded. Are you aware of any such cells?

There’s nothing wrong with having a powerful imagination. It’s just a shame that when a scientist like Tour points out the huge difference between the imaginary biology of OOL scenarios, and want is actually known to occur in nature, he catches so much flack for it.

Why should I, a biologist and biochemist, regard Miller as knowledgable?

Especially when Tour grossly misrepresents current OOL research, primarily by omitting most of it.

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Blockquote Why should I, a biologist and biochemist, regard Miller as knowledgable?

It depends on the subject now doesn’t it? Miller is a physicist, and I don’t know anyone who wants to understand the plausibility of a hypothetical chemical system who thinks that the calculations done by physicists are irrelevant to that endeavor. Do you? Besides you won’t want to give the appearance of resorting to a appeal to authority, as opposed to open mindedly considering the scientific evidence.

Fine then you should have no problem demonstrating this using Tour’s own paper linked below:

It does. That’s why I mentioned my expertise.

Really? Is he a practicing one? What are his accomplishments in physics? I suspect that you didn’t bother to check before touting him as an authority.

I love the way you moved the goalposts from Miller to physicists in general. Has Miller managed to publish any of his calculations?

I would venture to guess that you haven’t considered a single datum of actual evidence. You cite nothing but unqualified people, falsely presenting them as authorities. Why is that?

Easy. There’s nothing at all about respiration-first OOL hypotheses.

Here’s an excellent book by the leader in the field that Tour ignores:

Note that unlike any of the texts you have cited, this one was written by someone with actual accomplishments in the field.

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I consider the evidence. You and Tour and Miller don’t.

Here’s some evidence that they pretend doesn’t even exist. You’ve been completely conned, so much so that you’ll misrepresent your opinion as evidence-based on evidence, while misrepresenting mine as not based in evidence:

There is no actual reason to suppose that life’s origins are implausible.

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Assumes there is no physical-chemical process that can gradually give rise to a cellular state. In effect, that a cell must spontaneously form all at once or not at all. Baseless assumption.

All criticisms of the origin of life that attempt to undermine it’s plausibility are based on such baseless assumptions. Typically that the process must begin with the sort of instantaneous production of a self-sustaining cell.

I’m not aware they’re required to exist to for life to originate.

While on the topic of things we’re both unaware of, I know of no intelligent designer that isn’t also a cellular form of life.

Tour isn’t catching flak for “pointing out the huge difference between the imaginary biology of OOL scenarios, and what is actually known to occur in nature”.

Tour is catching flak for:
A) Making claims he can’t support (claiming flat out that life should not exist, for example).
B) Making grandiose extrapolations of essentially zero significance (declaring that because we haven’t found life on Mars, we shouldn’t expect to find it anywhere else).
C) For misrepresenting the state of the field because grandiose claims are made in the popular press(a problem in all branches of science).
D) Completely ignoring other parts of it(I’ve seen zero evidence that he’s even aware of the sort of work done by people like David Baum, or Nick Lane).
E) For his hypocrisy(complaining he doesn’t know what “spontaneous” means in chemistry when he uses the term himself in his own work).
F) For his painful ignorance of evolutionary biology (when he demands OOL explanations for attributes only found in eukaryotic cells).
G) Showing a picture of a barren, rocky desert claiming this represents all environments on the early Earth.

That’s just off the top of my head. There’s much more.

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“Calculations done by physicists” depend on whether those calculations involve unsubstantiated assumptions. But in this instance yes. Me and Jeremy England think Miller’s calculations tell us nothing about the origin of life.

Says the person literally invoking “Miller is a physicist”.

Zero mention of the entire branch of the field working on autocatalytic or metabolism-first systems. Again, people like Kavita Matange, David Baum, or Nick Lane’s research groups and their many different collaborators are completely absent in all his work.
Tour is obsessed with Jack Szostak and John Sutherland and their attempts to synthesize RNA monomers, and seems to labor under the misapprehension that is the only thing going on in the field.

So there you go.

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