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A Substantial Conundrum Confronting The Chemical Origin Of Life

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In ID circles we often discuss the sheer rarity of biologically relevant polypeptides with respect to combinatorial sequence space (and the related conundrum of macromolecular interdependence). It has often been argued that this represents a potent challenge to chemical origin-of-life models of an order substantially greater than the challenge it presents to biological evolution. There is one related problem in this regard which is often overlooked, and I want to briefly explore it in this blog entry.

When it comes to polymerization of amino acids to form proteins, two things must be borne in mind with regards to the formation of peptide bonds.

  1. Peptide bond formation is an endothermic reaction. This means that the reaction requires the absorption of energy: It does not take place spontaneously.
  2. Peptide bond formation is a condensation reaction. It hence involves the net removal of a water molecule. So not only can this reaction not happen spontaneously in an aqueous medium, but, in fact, the presence of water inhibits the reaction.

There is also the added problem of interfering cross-reactivity (the probability of interfering cross-reactions between the chemical groups on the various amino acid side chains is quite high).

But this is only the peak of the proverbial ice berg. The difficulties associated with synthesizing peptides (altogether with appropriate homochirality and all) are only half the story. There is also the problem of breaking the peptide bonds in order to generate a range of amino acid sequences in view of finding some with meaningful activity. I mentioned previously that the formation of a peptide bond requires a loss of a water molecule and the input of energy. On the flip side of the coin, then, breaking these bonds requires the addition of a water molecule and involves an energetically favorable reaction. But here’s the thing: Although this entails a net release of energy, the reaction involves high activation energy. But the activation energy for hydrolysis of peptide bonds is such that spontaneous hydrolysis under ambient conditions is not something which occurs readily.

In view of the difficulties associated with the making and breaking of peptide bonds, a very bleak picture is painted for the exploration of amino acid sequences in the pre-biotic context. Given that the conditions required for the making and breaking of peptide bonds are really quite different from one another, if naturalistic origin-of-life scenarios are to have any traction, it would entail that a location be required in which the conditions can vary significantly, alternating between conditions suitable for peptide bond formation and breaking. And this of course is compounded by the fact that the reactions, when they do occur, are likely to be slow and inefficient. Even granting that volcanoes and ocean vents might have provided the necessary changing conditions, it still stands to reason that the production of different polypeptides cannot have exceeded the rate of change of environmental conditions. This would dramatically limit the potential number of polypeptides which could have been produced in the prebiotic world, thus placing considerable restraints on the probabilistic resources at one’s disposal for the formation of multiple biologically relevant (and functionally interdependent) polypeptides.

In view of the reasons articulated above (and many others), the proteins-first model of the origin of life may be taken as essentially dead in the water. Not only are there the substantive challenges of even forming biologically relevant polypeptides. But even supposing that such prebiotic polymers could be produced in this way and useful sequences were happened across, the polymyers have to be able to reproduce with reasonable integrity. But there does not appear to be any way in which a polypeptide can determine a peptide sequence in some fashion analogous to that of base pairing of nucleic acids. How would these proteins be replicated in order to facilitate the workings of natural selection?

In view of the obvious closed-loop “catch-22” paradox of DNA making proteins and proteins making DNA, there is, of course, the fashionable scenario of the RNA world: That is to say, the possible role of RNA as the earliest hereditary macromolecule. This is seen to follow from the realization that RNA not only has information-carrying capacity, but also possesses catalytic capability. Proposed evidence for this notion included the fact that RNA makes up a large proportion of ribosomes (the protein factory of the cell). Furthermore, in eukaryotes (organisms with nucleated cells), components of genes which don’t code for proteins (called “introns”) are spliced out of an RNA transcript before translation. RNA molecules are involved in many of the RNA-splicing processes, and it has been documented that some RNA introns have self-splicing capability: that is to say, they can excise themselves, though at a slower rate than proteins can do it. Further observations which were taken as evidence for the plausibility of the RNA world thesis included the existence of RNA viruses, which use RNA as their genetic material which is translated directly into proteins.

Leaving aside the problems of attaining an RNA-based replicase (for that discussion, see Signature in the Cell), the problem is that the difficulties outlined above with regards the formation of polypeptides are really quite trivial in comparison to the difficulty of obtaining polynucleotides, in part because of the different kinds of bonds which need to be made and broken and the very different reaction conditions which are necessary at each stage. Nucleotides are composed of three chemical subunits – a ribose sugar, a phosphate group, and a nitrogenous base. Not only do these components need to be present and react together in an appropriate fashion in order to produce one nucleotide, but these nucleotides then have to be polymerized, a process which requires a series of endothermic condensation reactions, thereby requiring a high-energy condensing agent in order to perform them. In order to obtain nucleosides (i.e. base and ribose), one would need to begin with a mixture of nitrogenous bases and ribose and an appropriate condensing agents. To obtain nucleotides requires the mixing of nucleosides with phosphate and a different condensing agent.

The scenario for self-replicative capability of polynucleotides is more optimistic than that for polypeptides. But this is by no means trivial. At the heart of Darwinian rationale lies the concept that evolution must strike a balance between reliable reproduction of a species on the one hand, and opportunistic variation on the other. A poor replicator is much more likely to degrade through inaccurate copying than to be enhanced by evolution. There thus exists a threshold before the cumulative improvement of a replicator can occur by selection. A replicator must already have a reasonably good performance before it can even improve on that performance. At this point, however, we are running perilously close to yet another catch-22 conundrum: If (as I think is a legitimate assumption), this threshold performance level may be only attained with a sequence substantially longer than the minimum required for folding, one is faced with the even greater improbabilities of attaining such a replicator by a blind search.

Comments
A friend reminded me today, endothermic does not necessarily imply lack of spontaneity, and referred to the dissolution of ammonium chloride in water as a spontaneous, endothermic reaction. Rather, spontaneity occurs if and only if the change in Gibbs free energy is negative.ddb4chess
March 28, 2017
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Onlookers, cf here, in context and the onward links.kairosfocus
August 18, 2011
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FG You have been corrected on your direct and implied errors in the above many times, but have simply ignored correction. A note for record. GEM of TKIkairosfocus
August 18, 2011
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Extraordinary claims require extraordinary ADEQUATE evidence.kairosfocus
August 18, 2011
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It doesn't. Recently it was pointed out to me here that ID only draws design inferences from objects that we can directly study. First life is unavailable for direct study, therefore ID has nothing scientific to say about it. When ID supporters do speculate on the origin of life they are engaging in mataphysics, not science. At least that is what I took away from my conversations with Barry Arrington. fGfaded_Glory
August 17, 2011
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It said something like Sutherland took “half a base, half a ribose” and got them to combine, and that he had phosphorous present from the beginning. I would suspect that to get a “half of a sugar, and half of a base” requires some kind of lab set-up. Is it then feasible to think such segregating mechanisms were present somewhere on the earth? I would severely doubt it.
Why suspect, when you can look it up with a simple google search?
The Sutherland Group at the School of Chemistry, University of Manchester have demonstrated high yielding routes to cytidine and uridine ribonucleotides built from small 2 and 3 carbon fragments such as glycolaldehyde, glyceraldehyde or glyceraldehyde-3-phosphate, cyanamide and cyanoacetylene.
Calling these "half a sugar" or "half a base" isn't inaccurate but it's oversimplifying, as journalists do. It implied there is something unique and special about these compounds. In reality, these are just small, quite simple molecules that will occur when you add energy to a reducing environment with N and C in it. Like in Titan's atmosphere: http://www.google.com/search?hl=en&q=cyanoacetylene+titan&sourceid=navclient-ff&rlz=1B3GGGL_enUS239US239&ie=UTF-8 As for segregating mechanisms, the natural world is full of them, and it's not clear how much in terms of segregating mechanisms would be needed for Sutherland's pathway anyway. Certainly it needs much less segregation than a simple-minded "build a ribose, then build a base, then bring them together with phosphate" pathway would.NickMatzke_UD
August 17, 2011
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So how does ID explain the origin of life?paragwinn
August 17, 2011
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Dude! Read Jonathan M's latest article: http://www.evolutionnews.org/2011/08/new_scientist_weighs_in_on_ori049621.htmlmaterial.infantacy
August 17, 2011
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Start up a blog, challenge Darwinism, and watch the IDiots emerge?Mung
August 17, 2011
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I'll certainly be looking into it!;) Thanks for alerting me.PaV
August 17, 2011
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"One day soon, Sutherland says, someone will fill a container with a mix of primordial chemicals, keep it under the right conditions, and watch life emerge." New Scientist 2011 http://www.newscientist.com/article/mg21128251.300-first-life-the-search-for-the-first-replicator.html?page=3 These people are seriously deluded.idnet.com.au
August 17, 2011
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"Carl Sagan said “Extraordinary claims require extraordinary evidence”, and he was right about that." Actually, he wasn't right.Ilion
August 17, 2011
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And as it happens I have a blog post on this very topic going up first thing tomorrow morning on Evolution News & Views. JJonathan M
August 16, 2011
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Indeed. So true.Michael Servetus
August 16, 2011
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I wonder why Nick hasn't commented on this...tgpeeler
August 16, 2011
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Nick [17]: At New Scientist they have an article giving an overview of the RNA world hypothesis. They mention Sutherland's work. It said something like Sutherland took "half a base, half a ribose" and got them to combine, and that he had phosphorous present from the beginning. I would suspect that to get a "half of a sugar, and half of a base" requires some kind of lab set-up. Is it then feasible to think such segregating mechanisms were present somewhere on the earth? I would severely doubt it. So your claim that JohnnyM is "wrong" requires a huge kind of caveat. You, yourself, said: "I'm not saying Sutherland solved all questions about the origin of life . . ." Well, you could have, and probably should have, said: "I'm not saying Sutherland solved all questions about the mechanism whereby RNA nucleotides can form freely in nature...." But, of course, this would be to backtrack on your charge.PaV
August 16, 2011
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Cmon guys, JonathanM argued the following:
Nucleotides are composed of three chemical subunits – a ribose sugar, a phosphate group, and a nitrogenous base. Not only do these components need to be present and react together in an appropriate fashion in order to produce one nucleotide, but these nucleotides then have to be polymerized, a process which requires a series of endothermic condensation reactions, thereby requiring a high-energy condensing agent in order to perform them. In order to obtain nucleosides (i.e. base and ribose), one would need to begin with a mixture of nitrogenous bases and ribose and an appropriate condensing agents. To obtain nucleotides requires the mixing of nucleosides with phosphate and a different condensing agent.
...and it was directly falsified by Sutherland's work back in 2009. I'm not saying Sutherland solved all questions about the origin of life, or that all questions are answered. I'm just saying that one of JonathanM's arguments was blatantly wrong and uninformed to boot (well, several others were as well, but I'm not addressing those in this comment). In science you are supposed to admit mistakes, if you don't, well then, you're not doing science, you're doing propaganda.NickMatzke_UD
August 16, 2011
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Nick: ". . . a problem that, in fact, doesn’t exist in the latest, very well-known work?" Oh, boy. I hope you're not referring to the Sutherland work you cited? No problem exists; we've got it all under control; nothing to see here folks; move along . . .Eric Anderson
August 16, 2011
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Nick: Yes, actually I mention the paper you cite in a forthcoming blog entry concerning the recent article in New Scientist about the RNA World. Stephen Meyer said it well:
…Powner and colleagues only partially addressed the problem of generating the constituent building blocks of RNA under plausible pre-biotic conditions. The problem, ironically, is their own skillful intervention. To ensure a biologically-relevant outcome, they had to intervene--repeatedly and intelligently--in their experiment: first, by selecting only the right-handed isomers of sugar that life requires; second, by purifying their reaction products at each step to prevent interfering cross-reactions; and third, by following a very precise procedure in which they carefully selected the reagents and choreographed the order in which they were introduced into the reaction series. Thus, not only does this study not address the problem of getting nucleotide bases to arrange themselves into functionally-specified sequences, but the extent to which it does succeed in producing biologically-relevant chemical constituents of RNA actually illustrates the indispensable role of intelligence in generating such chemistry.
JJonathan M
August 16, 2011
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Nick, the experiment you cite do not represent plausible natural occcurences. The experiment is intelligently designed to produce the desired products: http://www.arn.org/blogs/index.php/literature/2009/05/19/ribonucleotides_and_the_revival_of_the_w http://crev.info/content/origin_of_life_claiming_something_for_almost_nothingkuartus
August 16, 2011
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As Louis Pasteur (Pasteur, 1848, 1922) showed in 1848, life is the only means capable of selecting molecules of only one-handedness.
Excellent point, but unfortunately, untrue. He showed quite the opposite.Petrushka
August 16, 2011
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"Douglas Axe comments on the experiment that “demonstrated” how RNA can replicate itself: “The humble truth is that the catalytic RNAs simply join two pre-made halves together by making a single new chemical bond. [2] What’s more, the molecular structure for accomplishing this joining is built into the precursors in such a way that 1) wrong ends cannot be joined, and 2) the energy for the correct joining is pre-supplied”" Yes, right, I forgot: unless a researcher can show how an event X could happen in an unbroken chain of events from the Big Bang on, their research results are worthless. What a bizarre view of science. The research showed how a specific event, that had been a conundrum before, could happen. A number of the precursor steps have already been shown to be possible / likely / provided for in the presumed conditions. Some are not yet. And in a research lab led by Polanyi, using assumptions that haven't been proven yet as ramifications for an experiment is apparently verboten. Good luck getting any research done, Polanyi. "“remedy”, ” team makes molecule” “final connection” Intelligent design(interference) is written all over this, it’s a mess, no seriously you cant make this stuff up." Seriously? You take the terminology used in a report about a research paper to claim that the conclusions of the research are "a mess"?molch
August 16, 2011
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Collin, "I’m extremely skeptical of scientific reports where scientists are commenting on their own research touting how it’s extremely strong evidence for whatever. Let neutral scientists comment on it and let’s see what they say." Why don't you read the actual scientific research papers, that have already been commented on by a number of scientists other than the authors?molch
August 16, 2011
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Nickmatzke, Even if ID-ers were doing what you allege, don't you see that you are DOING THE EXACT SAME THING? I mean, did you even read what Polyani wrote? And also, I'm extremely skeptical of scientific reports where scientists are commenting on their own research touting how it's extremely strong evidence for whatever. Let neutral scientists comment on it and let's see what they say.Collin
August 16, 2011
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Steve, I'm really curious about this. Considering that evolutionary principles and basic chemical principles (such as those used in Miller-Urey and the several thousand replications of Miller-Urey) are used in literally thousands of biological, chemical, economic, financial, engineering, computer science, process, and medical research programs, income based businesses, and important advances that many humans use on a daily basis all over the world... I would really like some evidence that any of this is being challenged in the 'marketplace of ideas' by ID. Can you name one tool, process, or product that is a direct result of the principles of ID (as promoted here on UD)?OgreMk5
August 16, 2011
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Our friend Nick writes: //This is another reason ID gets no cred in science.// vs the Philosopher of science Lakatos: "Scientists have thick skins. They do not abandon a theory [merely] because facts contradict it. They normally either invent some rescue hypothesis to explain what they then call a mere anomaly and if they cannot explain the anomaly, they ignore it, and direct their attention to other problems." I think Darwinian logic can be summed up like this: life looks designed because it's not.Polanyi
August 16, 2011
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Hmm, no one is willing to admit Jonathan M made a straight-up mistake in claiming a "conundrum" for a problem that, in fact, doesn't exist in the latest, very well-known work? This is another reason ID gets no cred in science. Its proponents circle the wagons and change the subject rather than admit a mistake.NickMatzke_UD
August 16, 2011
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"Instead, Sutherland’s team makes a molecule whose scaffolding contains a bond that will turn out to be the key ribose-base connection. Further atoms are then added around this skeleton, which unfurls to create the ribonucleotide." Did this happen spontaneously without intervention, or were the researchers carefully guiding and intervening to make this happen? It is hard to tell from this description. I note that Shapiro, in the linked news article, was singularly unimpressed.Eric Anderson
August 16, 2011
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Carl Sagan said "Extraordinary claims require extraordinary evidence", and he was right about that. Life-from-chemicals is a very extraordinary claim. Nick, would you say that the Miller-Urey and Sutherland experiments, along with the bits and pieces others have contributed, amount to "extraordinary evidence"?Gage
August 16, 2011
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Nick: I am an organic chemist and keep up with origin-of-life chemistry pretty well. In my opinion, the scraps of evidence for a chemical origin of life are light years from any plausible scenario. May I remind you that one of the world's OOL experts, George Whitesides of the Harvard OOL project says he has "no idea" how life could have gotten started (see http://pubs.acs.org/cen/coverstory/85/8513cover1.html, and scroll halfway down). Although as an atheist he believes OOL somehow happened, he finds all the theories implausible, including your favorite "RNA world" one. The magnitude of the problem (cellular complexity) has been growing rapidly for decades, while the "evidence" has been the straws a drowning materialist grasps at. The fact is that people who believe in a chemical OOL do so on philosophical grounds, not scientific ones. Whitesides is an honest materialist, honest enough (and secure enough) to call out the inadequacy of even his favorite notions.Gage
August 16, 2011
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