Defending the Christian Worldview, Creationism, and Intelligent Design
Would you like to react to this message? Create an account in a few clicks or log in to continue.
Defending the Christian Worldview, Creationism, and Intelligent Design

This is my personal virtual library, where i collect information, which leads in my view to the Christian faith, creationism, and Intelligent Design as the best explanation of the origin of the physical Universe, life, and biodiversity


You are not connected. Please login or register

Defending the Christian Worldview, Creationism, and Intelligent Design » Origin of life » The RNA & DNA World » RNA & DNA: It's prebiotic synthesis: Impossible !!

RNA & DNA: It's prebiotic synthesis: Impossible !!

Go down  Message [Page 1 of 1]

Otangelo


Admin

RNA & DNA: It's prebiotic synthesis: Impossible !!

https://reasonandscience.catsboard.com/t2865-rna-dna-it-s-prebiotic-synthesis-impossible

RNA & DNA: It's prebiotic synthesis: Impossible !! Part 1
https://www.youtube.com/watch?v=-ZFlmL_BsXE

RNA & DNA: It's prebiotic synthesis: Impossible !! Part 2
https://www.youtube.com/watch?v=dv4mUjmuRRU

Main points addressed in the video
Synthesis of nitrogenous bases in prebiotic environments
- High-energy precursors to produce purines and pyrimidines would have had to be produced in a sufficiently concentrated form. There is no known prebiotic route to this.  
- Scientists have failed to produce cytosine in spark-discharge experiments, nor has cytosine been recovered from meteorites or extraterrestrial sources. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.
- The origin of guanine bases has proven to be a particular challenge. While the other three bases of RNA  could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.
- Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine deaminates 37°C with a half-life of 80 years. Therefore, adenine would never accumulate in any kind of "prebiotic soup." The adenine-uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."
- Uracil has also a half-life of only 12 years at 100◦C. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition.
Ribose: Synthesis problems of the Pentose 5 carbon sugar ring
The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized for the ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons.
The phosphate group

On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.

Prebiotic RNA and DNA synthesis
1. No prebiotic mechanism is known to select:
- Right-handed configurations of RNA and DNA
- The right backbone sugar
- How to get size complementarity of the nucleotide bases to form a DNA strand and strands of the DNA molecule running in the opposite directions
2. Bringing all the parts together and joining them in the right position
- Attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place, and the backbone being a repetitive homopolymer
- Prebiotic glycosidic bond formation between nucleosides and the base
- Prebiotic phosphodiester bond formation
- Fine-tuning of the strength of the hydrogen base pairing forces
3. The instability, degradation, and asphalt problem
- Bonds that are thermodynamically unstable in water, and overall intrinsic instability. RNA’s nucleotide building blocks degrade at warm temperatures in time periods ranging from nineteen days to twelve years. These extremely short survival rates for the four RNA nucleotide building blocks suggest why life’s origin would have to be virtually instantaneous—all the necessary RNA molecules would have to be assembled before any of the nucleotide building blocks decayed.
4. The energy problem
- Doing things costs energy. There has to be a ready source of energy to produce RNA. In modern cells, energy is consumed to make RNA.
5. The minimal nucleotide quantity problem.
- The prebiotic conditions would have had to be right for reactions to give perceptible yields of bases that could pair with each other.
6. The Water Paradox  
- The hydrolytic deamination of DNA and RNA nucleobases is rapid and irreversible, as is the base-catalyzed cleavage of RNA in water. This leads to a paradox: RNA requires water to do its job, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place.
7.The transition problem from prebiotic to biochemical synthesis
- Even if all this in a freaky accident occurred by random events, that still says nothing about the huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network, where complex biosynthesis pathways produce nucleotides in modern cells.
Unguided prebiotic synthesis of RNA and DNA: an unsolved riddle!

I think, to say that on average the 14 hurdles that it would take to make primed nucleotides would each take 10 unit operations - that at least 140 little events would have to be appropriately sequenced. Unguided, the appropriate thing happened at each point on one occasion in six.The odds against a successful unguided synthesis of a batch of primed nucleotide on the primitive Earth would be a huge number, represented approximately by a 1 followed by 109 zeros ( 10^109). 'The odds are enormous against its being coincidence. No figures could express them.'

Synthesis of nitrogenous bases in prebiotic environments
- High-energy precursors to produce purines and pyrimidines would have had to be produced in a sufficiently concentrated form. There is no known prebiotic route to this.  
- Scientists have failed to produce cytosine in spark-discharge experiments, nor has cytosine been recovered from meteorites or extraterrestrial sources. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.
- The origin of guanine bases has proven to be a particular challenge. While the other three bases of RNA  could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.
- Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine deaminates 37°C with a half-life of 80 years. Therefore, adenine would never accumulate in any kind of "prebiotic soup." The adenine-uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."
- Uracil has also a half-life of only 12 years at 100◦C. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition.

Ribose: Synthesis problems of the Pentose 5 carbon sugar ring
The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized for the ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons.

The phosphate group
On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.

1. No prebiotic mechanism is known to select: 
- Right-handed configurations of RNA and DNA
- The right backbone sugar
- How to get size complementarity of the nucleotide bases to form a DNA strand and strands of the DNA molecule running in the opposite directions

2. Bringing all the parts together and joining them in the right position 
- Attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place, and the backbone being a repetitive homopolymer
- Prebiotic glycosidic bond formation between nucleosides and the base
- Prebiotic phosphodiester bond formation
- Fine-tuning of the strength of the hydrogen base pairing forces

3. The instability, degradation, and asphalt problem 
- Bonds that are thermodynamically unstable in water, and overall intrinsic instability. RNA’s nucleotide building blocks degrade at warm temperatures in time periods ranging from nineteen days to twelve years. These extremely short survival rates for the four RNA nucleotide building blocks suggest why life’s origin would have to be virtually instantaneous—all the necessary RNA molecules would have to be assembled before any of the nucleotide building blocks decayed.

4. The energy problem
- Doing things costs energy. There has to be a ready source of energy to produce RNA. In modern cells, energy is consumed to make RNA.

5. The minimal nucleotide quantity problem.
- The prebiotic conditions would have had to be right for reactions to give perceptible yields of bases that could pair with each other.

6. The Water Paradox  
- The hydrolytic deamination of DNA and RNA nucleobases is rapid and irreversible, as is the base-catalyzed cleavage of RNA in water. This leads to a paradox: RNA requires water to do its job, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place.

7.The transition problem from prebiotic to biochemical synthesis 
- Even if all this in a freaky accident occurred by random events, that still says nothing about the huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network, where complex biosynthesis pathways produce nucleotides in modern cells.

Synthesis of nitrogenous bases in prebiotic environments
- High-energy precursors to produce purines and pyrimidines would have had to be produced in a sufficiently concentrated form. There is no known prebiotic route to this.  
- Scientists have failed to produce cytosine in spark-discharge experiments, nor has cytosine been recovered from meteorites or extraterrestrial sources. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.
- The origin of guanine bases has proven to be a particular challenge. While the other three bases of RNA  could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.
- Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine deaminates 37°C with a half-life of 80 years. Therefore, adenine would never accumulate in any kind of "prebiotic soup." The adenine-uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."
- Uracil has also a half-life of only 12 years at 100◦C. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition.

Ribose: Synthesis problems of the Pentose 5 carbon sugar ring
The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized for the ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons.

The phosphate group
On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.

Unguided prebiotic synthesis of RNA and DNA: an unsolved riddle!
The origin of the RNA and DNA molecule is an origin of life problem, not evolution.
Steve Benner, one of the world’s leading authorities on abiogenesis:  The “origins problem” CANNOT be solved.
Graham Cairns-Smith: The odds against a successful unguided synthesis of a batch of primed nucleotide on the primitive Earth would be a huge number, represented approximately by a 1 followed by 109 zeros ( 10^109). 'The odds are enormous against its being coincidence. No figures could express them.'

Tan, Change; Stadler, Rob. The Stairway To Life
The longest chains (up to fifty monomers) and the highest production of molecules with the correct bonds have been achieved in the presence of montmorillonite clay. With purine nucleotides (adenosine and guanine), the percentage of correct phosphodiester bonds actually exceeded that of the incorrect bonds. However, the addition of each monomer to the chain comes with a probability of incorrect bonding, and one incorrect bond irreversibly destroys the homolinkage of the growing polymer, just as a train with one derailed boxcar can destroy the entire train. Therefore, the synthetic yield of biopolymers with the desired homolinkage decreases exponentially as the length of the biopolymer increases—even when starting only with pure building blocks.

In the presence of montmorillonite, polymerization of purine nucleotides (i.e., adenine and guanine) is favored over pyrimidine nucleotides (i.e., cytosine, thymine, and uracil) . This would constrain the potential information-carrying capacity of the resulting polymers, somewhat like requiring an author to have the letters A through M appear in their writing twice as often as the letters N through Z.

Another issue with the montmorillonite-catalyzed reaction is that the most successful polymerization occurred with an inosine nitrogenous base, which is not used to synthesize natural DNA or RNA. Also, the resulting oligomers decompose in the presence of water and the clay accelerates this decomposition.

Production of DNA with perfect homolinkage throughout the length of a genome (for example, there are approximately 500,000 nucleotides in the simplest known free-living organism’s genome) is impossible without the molecular machinery that is available only in living organisms.

An E. coli cell is about two micrometers long (two millionths of a meter) and one micrometer in diameter, and it contains a circular DNA molecule with 4.6 million base pairs. If fully extended, the DNA molecule would measure about 1.4 millimeters, or about 700 times longer than the E. coli cell. Picture your car, representing an E. coli, containing a rope that represents the DNA. Scaling up the E. coli to become the size of your car (about five meters or sixteen feet in length), the DNA would correspondingly scale up to approximately 3.5 kilometers or 2.2 miles of rope with a diameter of six millimeters or ¼ inch, contained in your car. Indeed, all of that DNA has to be compressed to fit within each bacterial cell. Now, imagine the E. coli cell duplicating this DNA before replication and needing to separate the two interlinked copies before cell division. Genomic DNAs are so long that they cannot fit into any cells without being highly compacted with the help of multiple proteins. Also, such a length of rope cannot be manipulated without kinking and supercoiling, especially when DNA is unwound for reproduction. Additional topoisomerase enzymes and structural maintenance of chromosome (SMC) proteins are essential for this purpose.


Prof. Steven A. Benner: When Did Life Likely Emerge on Earth in an RNA-First Process? 24 September 2019
All of these path‐hypotheses involve relatively reduced organic molecules that serve as the precursors of the four standard RNA nucleobases (guanine, adenine, cytosine, and uracil) or “grandfather′s axe” heterocycles (not shown). Thus, all assume the production of substantial amounts of reduced primary precursors, likely in the Hadean atmosphere (before 4 billion years ago). These primary precursors include hydrogen cyanide (HCN), cyanamide (H2NCN), cyanoacetylene (HCCCN), cyanogen (NCCN), ammonia (NH3), and cyanic acid (HCNO). Further, they all assume that these (or their downstream products) avoided dilution into a global ocean, perhaps by adsorbing on solids, or by delivery to sub‐aerial land with a constrained aquifer. Most chemical path‐hypotheses to create RNA prebiologically all but require an atmosphere that is more reducing than what planetary accretion models suggest was the norm above the Hadean Earth.
https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/syst.201900035

Prof. Steven A. Benner: Asphalt, Water, and the Prebiotic Synthesis of Ribose, Ribonucleosides, and RNA 2012
Some bonds in RNA appear to be “impossible” to form under any conditions considered plausible for early Earth
https://pubs.acs.org/doi/abs/10.1021/ar200332w

Henderson James Cleaves: One Among Millions: The Chemical Space of Nucleic Acid-Like Molecules  September 9, 2019
Various types of nucleic acid-like molecules have been enumerated and synthesized, but this is the first systematic attempt to enumerate, quantify and describe this chemical space. This space is surprisingly large, though its size appears predictable by typical isomerism studies. It is remarkable, given the existence of this structure space, that biology found a solution to the need for information storage. Is the solution life found to genetic molecular information storage optimal? In one sense obviously yes: it works very well and has managed to robustly support biological evolution over 3.5-4 Ga of planetary change. In another sense, from the standpoint of xeno- and synthetic biology, could other, perhaps equally good, or even better genetic systems be devised? The answer to this question will require sophisticated and protracted chemical experimentation. Studies to date suggest that the answer could be no. Many nearly as good, some equally good, and a few stronger base-pairing analogue systems are known.
https://pubs.acs.org/doi/10.1021/acs.jcim.9b00632

Graham Cairns-Smith: Genetic takeover,  page 66:
Now you may say that there are alternative ways of building up nucleotides, and perhaps there was some geochemical way on the early Earth. But what we know of the experimental difficulties in nucleotide synthesis speaks strongly against any such supposition. However it is to be put together, a nucleotide is too complex and metastable a molecule for there to be any reason to expect an easy synthesis. If you were to consider in more detail a process such as the purification of an intermediate ( to form amide bonds between amino acids and nucleotides ) you would find many subsidiary operations — washings, pH changes and so on. (Remember Merrifield’s machine: for one overall reaction, making one peptide bond, there were about 90 distinct operations required.)
https://3lib.net/book/2797668/0495a0

A. Graham Cairns-Smith: Chemistry and the Missing Era of Evolution 
What is missing from this story of the evolution of life on earth is the original means of producing such sophisticated materials as RNA. The main problem is that the replication of RNA depends on a clean supply of rather complicated monomers—activated nucleotides. What was required to set the scene for an RNA world was a highly competent, long-term means of production of at least two nucleotides. In practice the discrimination required to make nucleotide parts cleanly, or to assemble them correctly, still seems insufficient.
https://sci-hub.ren/10.1002/chem.200701215

Let us consider some of the difficulties to make RNA & DNA
1. as we have seen, it is not even clear that the primitive Earth would have generated and maintained organic molecules. All that we can say is that there might have been prevital organic chemistry going on, at least in special locations. 
2. highenergy precursors of purines and pyrimidines had to be produced in a sufficiently concentrated form (for example at least 0.01 M HCN). 
3. the conditions must now have been right for reactions to give perceptible yields of at least two bases that could pair with each other. 
4. these bases must then have been separated from the confusing jumble of similar molecules that would also have been made, and the solutions must have been sufficiently concentrated. 
5. in some other location a formaldehyde concentration of above 0.01 M must have built up. 
6. this accumulated formaldehyde had to oligomerise to sugars. 
7. somehow the sugars must have been separated and resolved, so as to give a moderately good concentration of, for example, D-ribose. 
8. bases and sugars must now have come together. 
9. Ninth, they must have been induced to react to make nucleosides. (There are no known ways of bringing about this thermo dynamically uphill reaction in aqueous solution: purine nucleosides have been made by dry phase synthesis, but not even this method has been successful for condensing pyrimidine bases and ribose to give nucleosides
10. Whatever the mode of joining base and sugar it had to be between the correct nitrogen atom of the base and the correct carbon atom of the sugar. This junction will fix the pentose sugar as either the a- or fl-anomer of either the furanose or pyranose forms. For nucleic acids it has to be the fl-furanose. (In the dry-phase purine nucleoside syntheses referred to above, all four of these isomers were present with never more than 8 ‘Z, of the correct structure.) 
11. phosphate must have been, or must now come to have been, present at reasonable concentrations. (The concentrations in the oceans would have been very low, so we must think about special situations—evaporating lagoons and such things  
12. the phosphate must be activated in some way — for example as a linear or cyclic polyphosphate — so that (energetically uphill) phosphorylation of the nucleoside is possible. 
13. to make standard nucleotides only the 5’- hydroxyl of the ribose should be phosphorylated. (In solid-state reactions with urea and inorganic phosphates as a phosphorylating agent, this was the dominant species to begin with. Longer heating gave the nucleoside cyclic 2’,3’-phosphate as the major product although various dinucleotide derivatives and nucleoside polyphosphates are also formed 
14. if not already activated — for example as the cyclic 2’,3’-phosphate — the nucleotides must now be activated (for example with polyphosphate) and a reasonably pure solution of these species created of reasonable concentration. Alternatively, a suitable coupling agent must now have been fed into the system. 
15. the activated nucleotides (or the nucleotides with coupling agent) must now have polymerised. Initially this must have happened without a pre-existing polynucleotide template (this has proved very difficult to simulate ; but more important, it must have come to take place on pre-existing polynucleotides if the key function of transmitting information to daughter molecules was to be achieved by abiotic means. This has proved difficult too. Orgel & Lohrmann give three main classes of problem. 
(i) While it has been shown that adenosine derivatives form stable helical structures with poly(U) — they are in fact triple helixes — and while this enhances the condensation of adenylic acid with either adenosine or another adenylic acid — mainly to di(A) - stable helical structures were not formed when either poly(A) or poly(G) Were used as templates. 
(ii) It was difficult to find a suitable means of making the internucleotide bonds. Specially designed water-soluble carbodiimides were used in the experiments described above, but the obvious pre-activated nucleotides — ATP or cyclic 2’,3’-phosphates — were unsatisfactory. Nucleoside 5'-phosphorimidazolides, for example: N/\ n K/N/P-r’o%OHN/\N were more successful, but these now involve further steps and a supply of imidazole, for their synthesis. 
(iii) Internucleotide bonds formed on a template are usually a mixture of 2’—5’ and the normal 3’—5’ types. Often the 2’—5’ bonds predominate although it has been found that Zn“, as well as acting as an eflicient catalyst for the templatedirected oligomerisation of guanosine 5’-phosphorimidazolide also leads to a preference for the 3’—5’ bonds. 
16. the physical and chemical environment must at all times have been suitable — for example the pH, the temperature, the M2+ concentrations. 
17. all reactions must have taken place well out of the ultraviolet sunlight; that is, not only away from its direct, highly destructive effects on nucleic acid-like molecules, but away too from the radicals produced by the sunlight, and from the various longer lived reactive species produced by these radicals. 
18. unlike polypeptides, where you can easily imagine functions for imprecisely made products (for capsules, ionexchange materials, etc), a genetic material must work rather well to be any use at all — otherwise it will quickly let slip any information that it has managed to accumulate. 
19. what is required here is not some wild one-off freak of an event: it is not true to say ‘it only had to happen once’. A whole set-up had to be maintained for perhaps millions of years: a reliable means of production of activated nucleotides at the least.

As the difficulties accumulate the stakes get higher: success would be all the more resounding, but it becomes less likely. Sooner or later it becomes wiser to put your money elsewhere.

RNA & DNA: It's prebiotic synthesis: Impossible !!  Adfasf10

Richard Van Noorden:  RNA world easier to make 13 May 2009
Although Sutherland has shown that it is possible to build one part of RNA from small molecules, objectors to the RNA-world theory say the RNA molecule as a whole is too complex to be created using early-Earth geochemistry. "The flaw with this kind of research is not in the chemistry. The flaw is in the logic — that this experimental control by researchers in a modern laboratory could have been available on the early Earth," says Robert Shapiro
Shapiro sides with supporters of another theory of life's origins – that because RNA is too complex to emerge from small molecules, simpler metabolic processes, which eventually catalysed the formation of RNA and DNA, were the first stirrings of life on Earth. Sutherland, though, hopes that ingenious organic chemistry might provide an RNA synthesis so convincing that it effectively serves as proof. "We might come up with something so coincidental that one would have to believe it," he says. "That is the goal of my career."
https://www.nature.com/articles/news.2009.471

Robert Shapiro: Life: What A Concept! 2008

SHAPIRO: Since then, so-called prebiotic chemistry, which is of course falsely named, because we have no reason to believe that what they're doing would ever lead to life — I just call it 'investigator influenced abiotic organic chemistry' — has fallen into the same trap. In the proceedings of the National Academy of Sciences about two months ago there was a paper — I think it was theoretical — they showed that in certain hydro-thermal events, convection forces and other attractive forces, about which I am unable to comment, would serve to concentrate organic molecules, so that organic molecules would get much more concentrated in the bottom of this than they would in the ordinary ocean. Very nice, perhaps it's a good place for the origin of life, and interesting finding, but then there was another commentary paper in the Proceedings by another invited commentator, who said, Great advance for RNA world because if you put nucleotides in, they'll be concentrated enough to form RNA; and if you put RNA in, the RNA will come together and form aggregates, giving you much more chance of forming a ribosome or whatever. I looked at the paper and thought, How did nucleotides come in? How did RNA come in? How did anything come in? The point is, you would take whatever mess prebiotic chemistry gives you and you would concentrate that mess so it's relevant to RNA or the origin of life — it's all in the eye of the beholder. And almost all of prebiotic chemistry is like this; they take chemicals of their own selection.

People were talking about Steve Benner and his borate paper where he selected, of his own free will, the chemical formaldehyde, the chemical acid-aldehyde, and the mineral borate, and he decided to mix them together and got a product that he himself said was significant in leading to the origin of RNA world, and I, looking at the same thing, see only the hands of Steve Benner reaching to the shelf of organic chemicals, picking formaldehyde, and from another shelf, picking acidaldehyde, etc. Excluding them carefully. Picking a mineral which occurs only in selective places on the Earth and putting it in in heavy doses. And at the end getting a complex of ribose and borate, which by itself would be of no use for making RNA, because the borate loves to hold onto the ribose, and as long as it holds onto the ribose it can't be used to make RNA. If it lets go of the ribose, then the ribose becomes vulnerable to destruction by all the other environmental agents. The half-life of pure ribose in solution, a different experiment and a very good one, by Stanley Miller is of the order of one or two hours, and all of the other sugars prominent in Earth biology have similar instability.

I was publishing papers like this and I got the reputation, or the nickname in the laboratory of the prebiotic chemist, of 'Dr. No'. If someone wanted a paper murdered, send it to me as a referee. And so on. At some point, someone said, Shapiro, you've got to be positive somewhere. So how did life start? And do we have any examples of authentic abiotic chemistry, not subject to investigator interference? The only true samples we have are those meteorites, which are scooped up quickly and often fallen in an unspoiled place — there was a famous meteorite that fell in France in a sheep field in the 1840s and led to dreadful chemistry of people seeing all sorts of bio molecules in it, not surprisingly. But if you took pristine meteorites and look inside, what you see are a predominance of simple organic compounds. The smaller the organic compound, the more likely it is to be present. The larger it is, the less likely it is to be present. Amino acids, yes, but the simplest ones. Over a hundred of them. All the simplest ones, some of which, coincidentally, overlap the unique set of 20 that coincide with Earth life, but not
containing the larger amino acids that overlap with Earth life. And no sample of a nucleotide, the building block of RNA or DNA, has ever been discovered in a natural source apart from Earth life. Or even take off the phosphate, one of the three parts, and no nucleoside has ever been put together. Nature has no inclination whatsoever to build nucleosides or nucleotides that we can detect, and the pharmaceutical industry has discovered this.

Life had to start with the mess — a miscellaneous mixture of organic chemistry to begin with. How do you organize this? You have to have a preponderance of some chemicals or lacking others would be against the second law of thermo-dynamics — it violates a concept that as a non-physicist that I barely grasp called 'entropy'.

In the simplest case, and there may be many more elaborate cases, they found that the energy wouldn't be released unless some chemical transformations took place. If the chemical transformations took place then the energy was released, a lot of it is heat. If this just went on continuously, all you do is use up the energy. Release all of it and you've converted one chemical to another. Big deal. To get things interesting, you have to close the cycle where the chemicals can be recycled by processes of their own, and then go through it again, releasing more energy. And once you have that, you can then develop nodes — because organic chemistry is very robust, there are reaction pathways leading everywhere, which is why it's such a mess.

One doesn't need a freak set of perhaps a hundred consecutive reactions that will be needed to make an RNA, and life becomes a probable thing that can be generated through the action of the laws of chemistry and physics, provided certain conditions are met. You must have the energy. It's good to have some container or compartment, because if your products just diffuse away from each other and get lost and cease to react with one another you'll eventually extinguish the cycle. You need a compartment, you need a source of energy, you need to couple the energy to the chemistry involved, and you need a sufficiently rich chemistry to allow for this network of pathways to establish itself. Having been given this, you can then start to get evolution.
https://jsomers.net/life.pdf

RNA & DNA: It's prebiotic synthesis: Impossible !!  Robert10


Michael Polanyi: “Life’s Irreducible Structure,” published in the journal Science in 1968:
“Suppose that the actual structure of a DNA molecule were due to the fact that the bindings of its bases were much stronger than the bindings would be for any other distribution of bases, then such a DNA molecule would have no information content. Its code-like character would be effaced by an overwhelming redundancy. […] Whatever may be the origin of a DNA configuration, it can function as a code only if its order is not due to the forces of potential energy. It must be as physically indeterminate as the sequence of words is on a printed page.”

To understand why random events are not a good explanation, we best have a look at the deepest level, on an atomic scale. Life uses just five nucleobases to make DNA and RNA. Two purines, and three pyrimidines. Purines use two rings with nine atoms, pyrimidines use just one ring with six atoms. Hydrogen bonding between purine and pyrimidine bases is fundamental to the biological functions of nucleic acids, as in the formation of the double-helix structure of DNA. This bonding depends on the selection of the right atoms in the ring structure. Pyrimidine rings consist of six atoms: 4 carbon atoms and 2 nitrogen atoms. Purines have nine atoms forming the ring: 5 carbon atoms and 4 nitrogen atoms.

Remarkably, it is the composition of these atoms that permit that the strength of the hydrogen bond that permits to join the two DNA strands and form Watson–Crick base-pairing, and well-known DNA ladder.  Neither transcription nor translation of the messages encoded in RNA and DNA would be possible if the strength of the bonds had different values. Hence, life, as we understand it today, would not have arisen.

Now, someone could say, that there could be no different composition, and physical constraints and necessity could eventually permit only this specific order and arrangement of the atoms. Now, in a recent science paper from 2019, Scientists explored how many different chemical arrangements of the atoms to make these nucleobases would be possible. Surprisingly, they found well over a million variants.   The remarkable thing is, among the incredible variety of organisms on Earth, these two molecules are essentially the only ones used in life. Why? Are these the only nucleotides that could perform the function of information storage? If not, are they perhaps the best? One might expect that molecules with smaller connected Carbon components should be easier for abiotic chemistry to explore.

According to their scientific analysis, the natural ribosides and deoxyribosides inhabit a fairly redundant ( in other words, superfluous, unnecessary, needless, and nonminimal region of this space.  This is a remarkable find and implicitly leads to design. There would be no reason why random events would generate complex, rather than simple, and minimal carbon arrangements. Nor is there physical necessity that says that the composition should be so. This is evidence that a directing intelligent agency is the most plausible explanation. The chemistry space is far too vast to select by chance the right finely-tuned functional life-bearing arrangement.

In the mentioned paper, the investigators asked if other, perhaps equally good, or even better genetic systems would be possible.  Their chemical experimentations and studies concluded that the answer is no. Many nearly as good, some equally good, and a few stronger base-pairing analog systems are known. There is no reason why these structures could or would have emerged in this functional complex configuration by random trial and error. There is a complete lack of scientific-materialistic explanations despite decades of attempts to solve the riddle.

What we can see is, that direct intervention, a creative force, the activity of an intelligent agency, a powerful creator, is capable to have the intention and implement the right arrangement of every single atom into functional structures and molecules in a repetitive manner, in the case of DNA, at least 500 thousand nucleotides to store the information to kick-start life, exclusively with four bases, to produce a storage device that uses a genetic code, to store functional, instructional, complex information, functional amino acids, and phospholipids to make membranes, and ultimately, life.  Lucky accidents, the spontaneous self-organization by unguided coincidental events, that drove atoms into self-organization in an orderly manner without external direction, chemical non-biological are incapable and unspecific to arrange atoms into the right order to produce the four classes of building blocks, used in all life forms.
https://sci-hub.ren/10.1126/science.160.3834.1308

David Denton stated:
We now know not only of the existence of a break between the living and non-living world but also that it represents the most dramatic and fundamental of all the discontinuities of nature. Between a living cell and the most highly ordered non-biological systems, such as a crystal or a snowflake, there is a chasm as vast and absolute as it is possible to conceive.

And Lynn Margulis stated: To go from a bacterium to people is less of a step than to go from a mixture of amino acids to a bacterium.

And Eugene Koonin advisory editorial board of Trends in Genetics stated:
A succession of exceedingly unlikely steps is essential for the origin of life, from the synthesis and accumulation of nucleotides to the origin of translation; through the multiplication of probabilities, these make the final outcome seem almost like a miracle. The difficulties remain formidable. For all the effort, we do not currently have coherent and plausible models for the path from simple organic molecules to the first life forms. Most damningly, the powerful mechanisms of biological evolution were not available for all the stages preceding the emergence of replicator systems. Given all these major difficulties, it appears prudent to seriously consider radical alternatives for the origin of life. "

And in fact, there are basically just two options to consider: Either life emerged by a lucky accident, spontaneously through self-organization by unguided natural events, or through the direct intervention, creative force, and activity of an intelligent designer. Evolution is not a possible explanation, because evolution depends on DNA replication. Many have claimed that physical necessity could have promoted chemical reactions, which eventually resulted in the emergence of life. The problem here however is, that the genetic sequence that specifies the arrangement of proteins can be of any order, there is no constraint by physical needs.

But RNA is also incredibly complex and sensitive, and some experts are skeptical that it could have arisen spontaneously under the harsh conditions of the prebiotic world.
https://www.quantamagazine.org/lifes-first-molecule-was-protein-not-rna-new-model-suggests-20171102/

Life before DNA: The origin and evolution of early archean cells
https://www.researchgate.net/publication/270759507_Life_before_DNA_The_origin_and_evolution_of_early_archean_cells

Signature in the Cell: Chapters 9 and 10
https://sfmatheson.blogspot.com/2010/04/signature-in-cell-chapters-9-and-10.html?fbclid=IwAR2a8Qvj7SpTB5_7mLMqisb671U7Tzk3b_UoVFUbioumc-5rAIMBwe5Cbm4

Rates of decomposition of ribose and other sugars: Implications for chemical evolution 
https://pdfs.semanticscholar.org/bfa2/d96d2adb03fa603f5cdac06dd0c922fb76da.pdf?_ga=2.14589559.1378959098.1615340959-1388763040.1615340959

The peptides would have been sticky assemblies of the amino acids that were spontaneously created in the primeval chemical soup; the short peptides would have then bound to one another, over time producing a protein capable of some sort of action. Tawfik, who is in the Institute's Biomolecular Sciences Department, says that is all well and good, "but one vital type of amino acid has been missing from that experiment and every experiment that followed in its wake: amino acids like arginine and lysine that carry a positive electric charge." These amino acids are particularly important to modern proteins, as they interact with DNA and RNA, both of which carry net negative charges. RNA is today presumed to be the original molecule that could both carry information and make copies of itself, so contact with positively-charged amino acids would theoretically be necessary for further steps in the development of living cells to occur.
https://www.sciencedaily.com/releases/2020/06/200622095023.htm




Further readings:
Biochemical fine-tuning - essential for life
https://reasonandscience.catsboard.com/t2591-biochemical-fine-tuning-essential-for-life

Chemical Etiology of Nucleic Acid Structure
http://sci-hub.ren/https://science.sciencemag.org/content/284/5423/2118

Formation of RNA Phosphodiester Bond by HistidineContaining Dipeptides
http://sci-hub.ren/https://onlinelibrary.wiley.com/doi/full/10.1002/cbic.201200643

Non-enzymatic Polymerization of Nucleic Acids from Monomers: Monomer SelfCondensation and Template-Directed Reactions
http://sci-hub.ren/https://www.eurekaselect.com/104564/article

New Twist Found in the Story of Life’s Start
https://www.quantamagazine.org/chiral-key-found-to-origin-of-life-20141126/

Chiral selection in poly(C)-directed synthesis of oligo(G)
http://sci-hub.ren/https://www.nature.com/articles/310602a0

Origins of building blocks of life: A review
https://www.sciencedirect.com/science/article/pii/S1674987117301305

Spontaneous formation and base pairing of plausible prebiotic nucleotides in water
https://www.nature.com/articles/ncomms11328

Ribose and related sugars from ultraviolet irradiation of interstellar ice analogs
http://sci-hub.ren/https://science.sciencemag.org/content/352/6282/208

Phosphodiester bond
https://en.wikipedia.org/wiki/Phosphodiester_bond

DNA & RNA: The foundation of life on Earth
http://xaktly.com/NucleicAcids.html

Life as a guide to prebiotic nucleotide synthesis
https://www.nature.com/articles/s41467-018-07220-y

The Quote Mine Project
http://www.talkorigins.org/faqs/quotes/mine/part2.html

Studies on the origin of life — the end of the beginning
http://sci-hub.ren/https://www.nature.com/articles/s41570-016-0012

The cosmological model of eternal inflation and the transition from chance to biological evolution in the history of life
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892545/

Prebiotic Systems Chemistry: Complexity Overcoming Clutter
https://www.cell.com/chem/fulltext/S2451-9294(17)30087-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451929417300876%3Fshowall%3Dtrue

Miller-Urey and Beyond: What Have We Learned About Prebiotic Organic Synthesis Reactions in the Past 60 Years?
http://sci-hub.ren/https://www.annualreviews.org/doi/abs/10.1146/annurev-earth-040610-133457

A Natural Origin-of-Life: Every Hypothetical Step Appears Thwarted by Abiogenetic Randomization
This is truly a top notch research paper on abiogenesis, where the authors deal with honesty about the problems, without sugar coat  it with evolutionary nonsense vocabulary. They go straight to the facts, expose the problems, and provide a honest conclusion.
https://osf.io/p5nw3/

Paradoxes in the origin of life
http://sci-hub.ren/https://www.ncbi.nlm.nih.gov/pubmed/25608919

Studies on the origin of life  the end of the beginning
http://sci-hub.ren/https://www.nature.com/articles/s41570-016-0012

Ring Structure for Ribose:
http://chemistry.elmhurst.edu/vchembook/543ribose.html
https://chem.libretexts.org/Bookshelves/Biological_Chemistry/Supplemental_Modules_(Biological_Chemistry)/Carbohydrates/Monosaccharides/Ribose

Ribonucleotides
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845210/

Exploring the Emergence of RNA Nucleosides and Nucleotides on the Early Earth
https://www.mdpi.com/2075-1729/8/4/57/htm

Evolutionist criticisms of the RNA World conjecture
https://creation.com/cairns-smith-detailed-criticisms-of-the-rna-world-hypothesis

Prebiotic chemistry and the origin of the RNA world.
http://sci-hub.ren/https://www.ncbi.nlm.nih.gov/pubmed/15217990

Robert Shapiro:  A Simpler Origin for Life February 12, 2007
https://www.scientificamerican.com/article/a-simpler-origin-for-life/?fbclid=IwAR0oMG32MWATWqtqg96hC-V4MEDAQAbW6oBcg_c_FNLxAUsmX8szZja5Mo8



Last edited by Otangelo on Thu Jun 02, 2022 1:33 pm; edited 162 times in total

https://reasonandscience.catsboard.com

Otangelo


Admin

Linking to science papers of more recent publication, did not justify you of accusing me of lying.  You made that accusation, without considering that I might have come to my conclusion based on older scientific information, which would eventually have been overturned with more recent, and new scientific findings. That is not so. 

Selective prebiotic formation of RNA pyrimidine and DNA purine nucleosides

Selective prebiotic formation of RNA pyrimidine and DNA purine nucleosides
https://sci-hub.st/https://www.nature.com/articles/s41586-020-2330-9

Claim: In contrast to all previous attempts to synthesize purine nucleosides, our synthesis is both prebiotically plausible and strictly stereo-, regio- and furanosyl-selective for the only isomer of the deoxypurine nucleosides used in modern biology. The pathway proceeds mostly via simple hydrolysis or dry-state processes, with a key reduction step promoted by UV irradiation supported by distinct mechanisms.
Reply:  That does not solve the problem of the lack of a mechanism to select  carbon and nitrogen in the nucleobases, outlined below:

https://reasonandscience.catsboard.com/t2865-rna-dna-it-s-prebiotic-synthesis-impossible#7700

Life uses just five nucleobases to make DNA and RNA. Two purines, and three pyrimidines. Purines use two rings with nine atoms, pyrimidines use just one ring with six atoms. Hydrogen bonding between purine and pyrimidine bases is fundamental to the biological functions of nucleic acids, as in the formation of the double-helix structure of DNA. This bonding depends on the selection of the right atoms in the ring structure. Pyrimidine rings consist of six atoms: 4 carbon atoms and 2 nitrogen atoms. Purines have nine atoms forming the ring: 5 carbon atoms and 4 nitrogen atoms.

Remarkably, it is the composition of these atoms that permit that the strength of the hydrogen bond that permits to join the two DNA strands and form Watson–Crick base-pairing, and well-known DNA ladder. Neither transcription nor translation of the messages encoded in RNA and DNA would be possible if the strength of the bonds had different values. Hence, life, as we understand it today, would not have arisen.

Now, someone could say, that there could be no different composition, and physical constraints and necessity could eventually permit only this specific order and arrangement of the atoms. Now, in a recent science paper from 2019, Scientists explored how many different chemical arrangements of the atoms to make these nucleobases would be possible. Surprisingly, they found well over a million variants. The remarkable thing is, among the incredible variety of organisms on Earth, these two molecules are essentially the only ones used in life. Why? Are these the only nucleotides that could perform the function of information storage? If not, are they perhaps the best? One might expect that molecules with smaller connected Carbon components should be easier for abiotic chemistry to explore.

According to their scientific analysis, the natural ribosides and deoxyribosides inhabit a fairly redundant ( in other words, superfluous, unnecessary, needless, and nonminimal region of this space. This is a remarkable find and implicitly leads to design. There would be no reason why random events would generate complex, rather than simple, and minimal carbon arrangements. Nor is there physical necessity that says that the composition should be so. This is evidence that a directing intelligent agency is the most plausible explanation. The chemistry space is far too vast to select by chance the right finely-tuned functional life-bearing arrangement.

In the mentioned paper, the investigators asked if other, perhaps equally good, or even better genetic systems would be possible. Their chemical experimentations and studies concluded that the answer is no. Many nearly as good, some equally good, and a few stronger base-pairing analog systems are known. There is no reason why these structures could or would have emerged in this functional complex configuration by random trial and error. There is a complete lack of scientific-materialistic explanations despite decades of attempts to solve the riddle.

Claim: Evidence implies that life may have started with a heterogeneous nucleic acid genetic system that included both RNA and DNA.
Reply: Even IF a prebiotic route of DNA synthesis would be found, the transition to an enzymatic biosynthesis pathway is a huge gap. How do you go from one to the other?
The replacement of RNA as the repository of genetic information by its more stable cousin, DNA, provides a more reliable way of transmitting information. DNA uses thymine (T) as one of its four informational bases, whereas RNA uses uracil (U).  At the C2' position of ribose, an oxygen atom is removed. The remarkable enzymes that do this are named Ribonucleotide reductases (RNR) The iron-dependent enzyme is essential for DNA synthesis, and most essential enzymes of life 32 , and it has one of the most sophisticated allosteric regulations known today. 50  
The thymine-uracil exchange constitutes one of the major chemical differences between DNA and RNA. Before being incorporated into the chromosomes, this essential modification takes place. Uracil bases in RNA are transformed into thymine bases in DNA. The synthesis of thymine requires seven enzymesDe novo biosynthesis of thymine is an intricate and energetically expensive process. 
All in all, not considering the metabolic pathways and enzymes required to make the precursors to start RNA and DNA synthesis requires at least 26  enzymes.

Open questions in prebiotic chemistry to explain the origin of the four basic building blocks of life

https://reasonandscience.catsboard.com/t1279p75-abiogenesis-is-mathematically-impossible#7759

One of the few biologists, Eugene Koonin, Senior Investigator at the National Center for Biotechnology Information, a recognized expert in the field of evolutionary and computational biology, is honest enough to recognize that abiogenesis research has failed. He wrote in his book: The Logic of Chance page 351:
" Despite many interesting results to its credit, when judged by the straightforward criterion of reaching (or even approaching) the ultimate goal, the origin of life field is a failure—we still do not have even a plausible coherent model, let alone a validated scenario, for the emergence of life on Earth. Certainly, this is due not to a lack of experimental and theoretical effort, but to the extraordinary intrinsic difficulty and complexity of the problem. A succession of exceedingly unlikely steps is essential for the origin of life, from the synthesis and accumulation of nucleotides to the origin of translation; through the multiplication of probabilities, these make the final outcome seem almost like a miracle.

Eliminative inductions argue for the truth of a proposition by demonstrating that competitors to that proposition are false. Either the origin of the basic building blocks of life and self-replicating cells are the result of the creative act by an intelligent designer, or the result of unguided random chemical reactions on the early earth. Science, rather than coming closer to demonstrate how life could have started, has not advanced and is further away to generating living cells starting with small molecules.  Therefore, most likely, cells were created by an intelligent designer.

I have listed  27 open questions in regard to the origin of RNA and DNA on the early earth, 27 unsolved problems in regard to the origin of amino acids on the early earth, 12 in regard to phospholipid synthesis, and also unsolved problems in regard to carbohydrate production. The open problems are in reality far greater. This is just a small list. It is not just an issue of things that have not yet been figured out by abiogenesis research, but deep conceptual problems, like the fact that there were no natural selection mechanisms in place on the early earth.  

The implausibility of prevital RNA and DNA  synthesis

How would prebiotic processes have purified the starting molecules to make RNA and DNA which were grossly impure? They would have been present in complex mixtures that contained a great variety of reactive molecules.
How did the Synthesis of the nitrogenic nucleobases in prebiotic environments occur?
How did fortuitous accidents select the five just-right nucleobases to make DNA and RNA, Two purines, and three pyrimidines?
How did unguided random events select purines with two rings, with nine atoms, forming the two rings: 5 carbon atoms and 4 nitrogen atoms, amongst almost unlimited possible configurations?
How did stochastic coincidence select pyrimidines with one ring, with six atoms, forming its ring: 4 carbon atoms and 2 nitrogen atoms, amongst an unfathomable number of possible configurations?
How did random trial and error foresee that this specific atomic arrangement of the nucleobases is required to get the right strength of the hydrogen bond to join the two DNA strands and form Watson–Crick base-pairing?
How did mechanisms without external direction foresee that this specific atomic arrangement would convey one of, if not the best possible genetic system to store information?
How would these functional bases have been separated from the confusing jumble of similar molecules that would also have been made?
How were high-energy precursors to produce purines and pyrimidines produced in a sufficiently concentrated form and joined to the assembly site?
How could the adenine-uracil interaction function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup" considering that its interaction is weak and nonspecific?
How could sufficient uracil nucleobases accumulate in prebiotic environments in sufficient quantities, if it has a half-life of only 12 years at 100◦C ?
How could the ribose 5 carbon sugar rings which form the RNA and DNA backbone have been selected, if 6 or 4 carbon rings, or even more or less, are equally possible but non-functional?
How could the formose reaction build the sugar portion of RNA from formaldehyde, if this reaction creates a mixture of sugars with varying sizes and shapes, of which ribose makes up less than 1%?
How would the functional ribose molecules have been separated from the non-functional sugars?
How were the correct nitrogen atom of the base and the correct carbon atom of the sugar selected to be joined together?
How could right-handed configurations of RNA and DNA have been selected in a racemic pool of right and left-handed molecules? Ribose must have been in its D form to adopt functional structures ( The homochirality problem )
How could random events have brought all the 3 parts together and bonded them in the right position ( probably over one million nucleotides would have been required ?)
How could prebiotic reactions have produced functional nucleosides? (There are no known ways of bringing about this thermodynamically uphill reaction in aqueous solution)
How could prebiotic glycosidic bond formation between nucleosides and the base have occurred if they are thermodynamically unstable in water, and overall intrinsically unstable?
How could  RNA nucleotides have accumulated, if they degrade at warm temperatures in time periods ranging from nineteen days to twelve years? These are extremely short survival rates for the four RNA nucleotide building blocks.
How was phosphate, the third element, concentrated at reasonable concentrations?. (The concentrations in the oceans or lakes would have been very low)
How would prebiotic mechanisms phosphorylate the nucleosides at the correct site (the 5' position) if, in laboratory experiments, the 2' and 3' positions were also phosphorylated?
How could phosphate have been activated somehow? In order to promote the energy dispendious nucleotide polymerization reaction, and (energetically uphill) phosphorylation of the nucleoside had to be possible.
How was the energy supply accomplished to make RNA? In modern cells, energy is consumed to make RNA.
How could a transition from prebiotic to biochemical synthesis have occurred? There are a huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network.
How could  RNA have formed, if it requires water to make them, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place?
How would the prebiotic synthesis transition of RNA to the highly regulated cellular metabolic synthesis have occurred?  The pyrimidine synthesis pathway requires six regulated steps, seven enzymes, and energy in the form of ATP.
The starting material for purine biosynthesis is Ribose 5-phosphate, a product of the highly complex pentose phosphate pathway, which uses 12 enzymes. De novo purine synthesis pathway requires ten regulated steps, eleven enzymes, and energy in the form of ATP.

DNA is more stable than RNA. uracil (U) is replaced in DNA by thymine (T)
At the C2' position of ribose, an oxygen atom is removed by hypercomplex RNR molecular machines. The thymine-uracil exchange is the major chemical difference between DNA and RNA. Before being incorporated into the chromosomes, this essential modification takes place. The synthesis of thymine requires seven enzymes. De novo biosynthesis of thymine is an intricate and energetically expensive process.
All in all, not considering the metabolic pathways and enzymes required to make the precursors to start RNA and DNA synthesis, at least 26  enzymes are required. How did these enzymes emerge, if DNA is required to make them?

So, you need 26 enzymes to make DNA. But you need enzymes to make DNA. What came first?

The synthesis of ribonucleotides RNA requires the following steps:

- synthesis of the bases
- synthesis of ribose
- bonding the bases to ribose
- bonding phosphate to the nucleosides
- activation of nucleotides
- polymerization to make oligonucleotides

RNA & DNA: It's prebiotic synthesis: Impossible !!  Inorga10

Leslie E. Orgel: Self-organizing biochemical cycles  2000 Nov 7
How were ribonucleotides first formed on the primitive earth? This is a very difficult problem. Stanley Miller's synthesis of the amino acids by sparking a reducing atmosphere (2) was the paradigm for prebiotic synthesis for many years, so at first, it was natural to suppose that similar methods would meet with equal success in the nucleotide field. However, nucleotides are intrinsically more complicated than amino acids, and it is by no means obvious that they can be obtained in a few simple steps under prebiotic conditions. A remarkable synthesis of adenine (3) and more or less plausible syntheses of the pyrimidine nucleoside bases (4) have been reported, but the synthesis of ribose and the regiospecific combination of the bases, ribose, and phosphate to give β-nucleotides remain problematical.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18793/

Robert Shapiro Do natural clays catalyze this reaction? June 2006
The attractiveness of this oligonucleotide synthesis rests in part in the ready availability of the catalyst. Montmorillonite is a layered clay mineral-rich in silicate and aluminum oxide bonds. It is widely distributed in deposits on the contemporary Earth. If the polymerization of RNA subunits was a common property of this native mineral, the case for RNA at the start of life would be greatly enhanced.
However, the “[c]atalytic activity of native montmorillonites before being converted to their homoionic forms is very poor” (Ertem 2004:567). The native clays contain bound polyvalent cations, such as Cu2, Fe3, and Zn2, that interfere with phosphorylation reactions. This handicap was overcome in the synthetic experiments by titrating the clays to a monoionic form, generally sodium, before they were used. Even after this step, the activity of the montmorillonite depended strongly on its physical source, with samples from Wyoming yielding the best results (Ferris et al. 1989; Ertem 2004). Eventually the experimenters settled on Volclay, a commercially processed Wyoming montmorillonite provided by the American Colloid Company. Further purification steps were applied to obtain the catalyst used for the “prebiotic” formation of RNA.
https://www.jstor.org/stable/10.1086/506024

David Deamer Where Did Life Begin? Testing Ideas in Prebiotic Analogue Conditions 10 February 2021 5
The polymerization results must still be classified as preliminary, however, because the exact chemical structures of the polymers formed from ribonucleotides have not been elucidated.
https://www.mdpi.com/2075-1729/11/2/134/htm

It is also certain that they are polyanions resembling RNA because they readily migrate during gel electrophoresis. Furthermore, they are recognized by the enzymes used for end labeling with P-32-ATP [url=https://reasonandscience.catsboard.com/Lipid-assisted synthesis of RNA-like polymers from mononucleotides]4[/url]
https://sci-hub.ren/10.1007/s11084-007-9113-2

Sudha Rajamani: Lipid-assisted synthesis of RNA-like polymers from mononucleotides 2008 Feb 4 : 16 November 2007
Here we show that RNA-like polymers can be synthesized non-enzymatically from mononucleotides in lipid environments.

My comment: This presupposes that there actually was a lipid environment. This is an unwarranted assumption. And polymerization also assumes that right-handed RNAs were readily concentrated and available. Another unwarranted assumption. And it assumes that RNA's had a "natural" drive or tendency to polymerize. Another unwarranted assumption.

Synthesis of phosphodiester bonds is driven by the chemical potential of fluctuating anhydrous and hydrated conditions, with heat providing activation energy during dehydration.

My comment:  Phosphate must still be activated in some way — for example as a linear or cyclic polyphosphate — so that (energetically uphill) phosphorylation of the nucleoside is possible. There is no explanation of how this could have occurred prebiotically in the paper. It is just taken as a given. To make standard nucleotides only the 5’- hydroxyl of the ribose has to be phosphorylated. There is nothing that prevents the nucleoside cyclic 2’,3’-phosphate as the major product, and even further, various dinucleotide derivatives and nucleoside polyphosphates are also formed which is an additional problem.  Furthermore, the nucleotides must now be activated (for example with polyphosphate) and a reasonably pure solution of these species created of reasonable concentration. Alternatively, a suitable coupling agent would have had to be fed into the system. There is no feasible explanation where it could have come from prebiotically.  Then, the activated nucleotides (or the nucleotides with coupling agent) have to polymerize now. Initially, this would have had to happen without a pre-existing polynucleotide template (this has proved very difficult to simulate; The BIG problem here is, the pre-existing polynucleotides if the key function of transmitting information to daughter molecules had to be achieved by abiotic means.

In the final hydration step, the RNA-like polymer is encapsulated within lipid vesicles.

My comment: How would that have occurred prebiotically? There have to be made many unwarranted assumptions. 1. A viable lipid vesicle had to be ready available 2. There had to be some reasons for this process to occur. 3. And even if that event happened, the "protocell" would soon disintegrate in its individual components, and become tar.

Each group of 4 vials contained a specific set of nucleotides, which in some samples were mixed with several kinds of amphiphilic molecules.

My comment: They started their experiments with nucleotides. These were not readily available prebiotically. The formation of such is a huge problem, most commonly not sufficiently acknowledged: Here the list:

Open questions in prebiotic chemistry to explain the origin of the four basic building blocks of life
https://reasonandscience.catsboard.com/t1279p75-abiogenesis-is-mathematically-impossible#7759

The total concentration of all mononucleotides was 10 mM in the original solutions.

My comment: There was neither a selection, nor concentration mechanism extant on the prebiotic earth.

We found that significant amounts of polymers had been synthesized with UV spectra matching those expected from the mixed nucleotides. Yields ranged from 50 to 300 mg depending on which nucleotides were present in the mixture. Lower yields were observed if AMP was present, either by itself or in mixtures (50–100 μg total) while higher yields were obtained with UMP by itself (150–300 μg).

My comment: Granted that by the method employed small strands were polymerized, the aforementioned hurdles and unbridgeable problems turn this finding meaningless in face of the end goal, which is to produce information-bearing DNA strands.

RNA & DNA: It's prebiotic synthesis: Impossible !!  Shapir10

Andro C. Rios: On the Origin of the Canonical Nucleobases: An Assessment of Selection Pressures across Chemical and Early Biological Evolution 2013 June
Evidence suggests that many types of heterocycles ( nucleobases) could have been present on the early Earth.
The native bases of RNA and DNA are prominent examples of the narrow selection of organic molecules upon which life is based.

Question: How were the four nucleobases selected, if there was no evolutionary natural selection extant prior to when life began?

How did nature “decide” upon these specific heterocycles?

Question: Non-mental matter does not have the ability to make decisions.

It is therefore likely that the contemporary composition of nucleobases is a result of multiple selection pressures that operated during early chemical and biological evolution.

Question: Why is that likely? Is that not a just so, an ad-hoc assertion without evidence? a red herring? 

The persistence of the fittest heterocycles in the prebiotic environment towards, for example, hydrolytic and photochemical assaults, may have given some nucleobases a selective advantage for incorporation into the first informational polymers.

Question: It is observable, how evolutionary vocabulary is smuggled in into abiogenesis research. There was no evolutionary fitness prior when life began. 

The prebiotic formation of polymeric nucleic acids employing the native bases remains, however, a challenging problem to reconcile.

Question: There is no problem if we permit the inference of intelligent design, though.

Two such selection pressures may have been related to genetic fidelity and duplex stability. 

Question: There was no need for monomers to form DNA duplex forms.

The amino groups of the nucleobases in the native alphabet are absolutely essential to maintaining the fidelity of genetic information. Spontaneous deamination reactions are thus highly deleterious

https://onlinelibrary.wiley.com/doi/abs/10.1002/ijch.201300009



Origin of prebiotic nucleotides - a viable hypothesis?
https://reasonandscience.catsboard.com/t2964-origin-of-prebiotic-nucleotides-a-viable-hypothesis

DNA: Destroys the theory of Evolution. Unmasking the lies
https://reasonandscience.catsboard.com/t2719-dna-origin-of-life-scenarios#6124

Prevital unguided origin of the four basic building blocks of life: Impossible !!
https://reasonandscience.catsboard.com/t2894-prevital-unguided-origin-of-the-four-basic-building-blocks-of-life-impossible



Last edited by Otangelo on Sat May 14, 2022 6:24 am; edited 72 times in total

https://reasonandscience.catsboard.com

Otangelo


Admin

RNA & DNA: It's prebiotic synthesis: Impossible !!  


RNA & DNA: It's prebiotic synthesis: Impossible !!  013

RNA & DNA: It's prebiotic synthesis: Impossible !!  2212
James Watson at left and Francis Crick discovered the structure of the DNA (deoxyribonucleic acid) molecule in 1953.  DNA are the molecules which make up the “alphabet” which specifies biological heredity.  DNA are the molecules which store the blueprint of life, and as such, hold a central indispensable position.

The RNA polymerase machine complex transcribes the instructional information stored in DNA into RNA. RNA is built of (almost) the same four-letter alphabet as DNA. It is more fragile, and as such, it could also be an information carrier, but less adequate long term.

Who wants to find answers about how life started, needs to find compelling explanations about how RNA and DNA first emerged on earth. In all known living beings, genetic information flows from DNA to RNA to proteins

RNA & DNA: It's prebiotic synthesis: Impossible !!  2312
Their work on the structure of DNA was performed with some access to the X-ray crystallography of Maurice Wilkins and Rosalind Franklin at King's College London. Combining all of this work led to the deduction that DNA exists as a double helix. This information was critical for their further progress. They obtained this information as part of a report by Franklin to the Medical Research Council. 

The report was by no means secret, but it put the critical data on the parameters of the helix (base spacing, helical repeat, number of units per turn of the helix, and diameter of the helix) in the hands of two who had contributed none of those data. 

With this information, they could begin to build realistic models. The big problem was where to put the purine and pyrimidine bases. Details of the diffraction pattern indicated two strands, and indicated that the relatively massive phosphate ribose backbones must be on the outside, leaving the bases in the center of the double helix.

RNA & DNA: It's prebiotic synthesis: Impossible !!  2411
Crick, Watson and Wilkins shared the 1962 Nobel Prize for Physiology or Medicine, Franklin having died of cancer in 1958.

RNA & DNA: It's prebiotic synthesis: Impossible !!  1a10
Four major classes of organic molecules are found in living cells. All forms of life have organic molecules and macromolecules that fall into these four broad categories, based on their chemical and biological properties: carbohydrates, lipids, proteins, and nucleic acids. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  7513
Nucleotides are essential to cellular metabolism, and nucleic acids are the molecules of genetic information storage and expression.

General description of the structure of the RNA and DNA molecule


DNA is the molecule of life, which contains the blueprint, or instructions to make for example proteins that perform most life functions. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  2811

Nucleotides are building blocks for DNA and RNA. The two classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA molecules store genetic information coded in the sequence of their building blocks.  

DNA can be considered as a modified form of RNA since the ribose sugar in RNA is transformed into deoxyribose in DNA at the 5 prime positions ( see the red circle in the picture above ), and the uracil base is methylated into thymidine ( More about this, later). The structural difference between these sugars is that ribonucleic acid contains a hydroxyl (-OH) group, whereas deoxyribonucleic acid contains only a hydrogen atom in the place of this hydroxyl group.

RNA & DNA: It's prebiotic synthesis: Impossible !!  1511
Nucleotides which contain deoxyribonucleic acid are known as deoxyribonucleotides.  Those containing ribonucleic acid are known as ribonucleotides. Thus, the sugar molecule determines whether a nucleotide forms part of a DNA molecule or a RNA molecule. 

These molecules consist of three components: a phosphate, a ribose sugar, and a nitrogenous (nitrogen-containing) ring compound that behaves as a base.  The nucleotide is the repeating structural unit of both DNA and RNA. 

The picture shows the repeating unit of nucleotides found in DNA and RNA. DNA and RNA contain deoxyribose and ribose respectively as its sugar and the bases attached. The locations of the attachment sites of the base and phosphate to the sugar molecule are important to the nucleotide’s function, and how prebiotic events supposedly came up with the right configuration is one of the unsolved riddles. 

The nitrogenous base
RNA & DNA: It's prebiotic synthesis: Impossible !!  7312




RNA & DNA: It's prebiotic synthesis: Impossible !!  1413
Nucleotide bases appear in two forms: A single-ring nitrogenous base, called a pyrimidine, and a double-ringed base, called a purine.


RNA & DNA: It's prebiotic synthesis: Impossible !!  2c10



High-energy precursors to produce purines and pyrimidines would have had to be produced in a sufficiently concentrated form. There is no known prebiotic route to this.  

Scientists have failed to produce cytosine in spark-discharge experiments, nor has cytosine been recovered from meteorites or extraterrestrial sources. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses. 

The origin of guanine bases has proven to be a particular challenge. While the other three bases of RNA  could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.

Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine deaminates 37°C with a half-life of 80 years. Therefore, adenine would never accumulate in any kind of "prebiotic soup." The adenine-uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."

Uracil has also a half-life of only 12 years at 100◦C. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition.

Ribose: The Pentose 5 carbon sugar ring of RNA and DNA

RNA & DNA: It's prebiotic synthesis: Impossible !!  1611

DNA has the ribose sugar in RNA transformed into deoxyribose in DNA at the 2 prime positions. A base is attached to the 1 prime carbon atom, and a phosphate group is attached at the 5 prime positions. Compared with ribose, deoxyribose lacks a single oxygen atom at the 2 prime positions; the prefix deoxy- (meaning without oxygen) refers to this missing atom.

RNA & DNA: It's prebiotic synthesis: Impossible !!  3211

The pentose sugar is a 5-carbon monosaccharide. These form two groups: aldopentoses and ketopentoses. The pentose sugars found in nucleotides are aldopentoses. Deoxyribose and ribose are two of these sugars. A DNA strand is formed when the nitrogenous bases are joined by hydrogen bonds, and the phosphates of one group are joined to the pentose sugars of the next group with a phosphodiester bond.

Ribose is a monosaccharide containing five carbon atoms. d-ribose is present as the six different forms. The β-d-furanose form is extensively used in biological systems as a component of RNA. The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction.

Several problems have been recognized for the ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons.

RNA & DNA: It's prebiotic synthesis: Impossible !!  6610
The reality of the formose reaction is that it descends into an inextricable mixture. The vast array of sugars produced is overwhelming and the intrinsic lack of selectivity for ribose is its undoing. Ultimately, the formose reaction produces a disastrously complex mixture of linear and branched aldo and keto-sugars in the racemic forms.

The consequences of such uncontrolled reactivity is that ribose is formed in less than 1% yield among a plethora of isomers and homologs. The instability of ribose prevents its accumulation and requires it to undergo extremely rapid onward conversion to ribonucleosides before the free sugar is lost to rapid degradation. 

There are no further alternatives: Either chance "choose" by lucky random events the five-membered ring ribofuranose backbone for DNA and RNA, or it was a choice by intelligence with specific purposes. What makes more sense?

This reaction requires a high concentration of  Formaldehyde, which, however, readily undergoes a variety of reactions in aqueous solutions. Another problem is that ribose is unstable and rapidly decomposes in water. 

Furthermore, as Stanley Miller and his colleagues recently reported, "ribose and other sugars have surprisingly short half-lives for decomposition at neutral pH, making it very unlikely that sugars were available as prebiotic reagents."

RNA & DNA: It's prebiotic synthesis: Impossible !!  7711
Leslie Orgel concludes: Some progress has been made in the search for an efficient and specific prebiotic synthesis of ribose and its phosphates. However, in every scenario, there are still a number of obstacles to the completion of a synthesis that yields significant amounts of sufficiently pure ribose in a form that could readily be incorporated into nucleotides.

RNA & DNA: It's prebiotic synthesis: Impossible !!  3510
There have been a wide variety of attempts and proposals to try to solve the riddle, but up to date, without success. The article in Science magazine from 2016 admits: Ribose is the central molecular subunit in RNA, but the prebiotic origin of ribose remains unknown.

And a recent research paper from 2018 reports: Even if some progress has been made to understand the ribose formation under prebiotic conditions, each suggested route presents obstacles, limiting ribose yield and purity necessary to form nucleotides. A selective pathway has yet to be elucidated.

The third component of a nucleotide is a phosphate group

RNA & DNA: It's prebiotic synthesis: Impossible !!  7911
Phosphorus is the third essential element making part of the structures of DNA and RNA. It is perfect to form a stable backbone for the DNA molecule. Phosphates can form two phosphodiester bonds with two sugars at the same time and connect two nucleotides. Phosphorus is difficult to dissolve, and that would be a problem both in an aquatic as-as well on a terrestrial environment.

Phosphoesters form the backbone of DNA molecules. A phosphodiester bond occurs when exactly two of the hydroxyl groups in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds.

RNA & DNA: It's prebiotic synthesis: Impossible !!  7611
Phosphodiester bonds are central to all life on Earth as they make up the backbone of the strands of nucleic acid. In DNA and RNA, the phosphodiester bond is the linkage between the 3' carbon atom of one sugar molecule and the 5' carbon atom of another, deoxyribose in DNA and ribose in RNA. Strong covalent bonds form between the phosphate group and two ribose 5-carbon rings over two ester bonds. 

On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction. 

That adds up to the fact that concentrations on earth are very low.  So far, no geochemical process that led to abiotic production of polyphosphates in high yield on the Earth has been discovered. 

The phosphate is connected to ribose which is connected to the nitrogenous base. Each of the 3 parts of nucleotides must be just right in size, form, and must fit together. The bonds must have the right forces in order to form the spiral form DNA molecule. And there would have to be enough units concentrated at the same place on prebiotic earth of the four bases in order to be able to form a self-replicating RNA molecule if the RNA world is supposed to be true.

RNA & DNA: It's prebiotic synthesis: Impossible !!  1112
A nucleotide is differentiated from a nucleoside by one phosphate group. Accordingly, a nucleotide can also be a nucleoside monophosphate. If more phosphates bond to the nucleotide (nucleoside monophosphate) it can become a nucleoside diphosphate (if two phosphates bond), or a nucleoside triphosphate (if three phosphates bond), such as adenosine triphosphate (ATP). 

RNA & DNA: It's prebiotic synthesis: Impossible !!  8011
Adenosine triphosphate, or ATP, is the energy currency in the cell, a crucial component of respiration and photosynthesis, amongst other processes.

The base, sugar, and phosphate need to be joined together correctly - involving two endothermic condensation reactions involved in joining the nucleotides, which means it has to absorb energy from its surroundings. In other words, compared with polymerization to make proteins, nucleotides are even harder to synthesize and easier to destroy; in fact, to date, there are no reports of nucleotides arising from inorganic compounds in primaeval soup experiments. 



Prebiotic RNA and DNA synthesis


RNA & DNA: It's prebiotic synthesis: Impossible !!  6210
What must be explained, is the origin and prebiotic making of nucleotides, that is adenine, guanine, cytosine,  uracil and thymine and the transition to enzymatic biosynthesis of these. 

The emergence in the 1980s of the RNA world as a major theory for the origin of life led to increased attention on the prebiotic synthesis of simple RNA and RNA-like molecules. RNA is a complex, polymeric structure. But its prebiotic synthesis faces many problems, of which we will give a closer look just to a few. 

1. Selecting the right components
1a. Selecting right-handed configurations of RNA and DNA
1b. Selecting the right backbone sugar
1c. Size Complementarity of the nucleotide bases to form a DNA strand and strands of the DNA molecule running in the opposite directions

2. Bringing all the parts together and joining them in the right position Attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place, and the backbone being a repetitive homopolymer
2a. Glycosidic bond formation between nucleosides and the base
2b. Prebiotic phosphodiester bond formation
2c. Fine-tuning of the strength of the hydrogen base pairing forces

3. The instability, degradation, and asphalt problem Bonds that are thermodynamically unstable in water, and overall intrinsic instability. RNA’s nucleotide building blocks degrade at warm temperatures in time periods ranging from nineteen days to twelve years. These extremely short survival rates for the four RNA nucleotide building blocks suggest why life’s origin would have to be virtually instantaneous—all the necessary RNA molecules would have to be assembled before any of the nucleotide building blocks decayed.

4. The energy problem: Doing things costs energy. There has to be a ready source of energy to produce RNA. In modern cells, energy is consumed to make RNA. 

5. The minimal nucleotide quantity problem.  The prebiotic conditions would have had to be right for reactions to give perceptible yields of bases that could pair with each other.

6. The Water Paradox:  The hydrolytic deamination of DNA and RNA nucleobases is rapid and irreversible, as is the base-catalyzed cleavage of RNA in water. This leads to a paradox: RNA requires water to do its job, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place.

7 .The transition problem from prebiotic to biochemical synthesis Even if all this in a freaky accident occurred by random events, that still says nothing about the huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network, where  complex biosynthesis pathways produce nucleotides in modern cells.


1. Selecting the right components

1a. Selecting right-handed configurations of RNA and DNA
Once the three components would have been synthesized prebiotically, they would have had to be separated from the confusing jumble of similar molecules nearby, and they would have had to become sufficiently concentrated in order to move to the next steps, to join them to form nucleosides, and nucleotides. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  2511
At a chemical level, a deep bias permeates all of biology. The molecules that make up DNA and other nucleic acids such as RNA have an inherent “handedness.” These molecules can exist in two mirror-image forms, but only the right-handed version is found in living organisms. Handedness serves an essential function in living beings; many of the chemical reactions that drive our cells only work with molecules of the correct handedness.

DNA takes on this form for a variety of reasons, all of which have to do with intermolecular forces. The phosphate/ribose backbone of DNA is hydrophilic (water-loving), so it orients itself outward toward the solvent, while the relatively hydrophobic bases bury themselves inside.

Additionally, the geometry of the deoxyribose-phosphate linkage allows for just the right pitch, or distance between strands in the helix, a pitch that nicely accommodates base pairing. Lots of things come together to create the beautiful right-handed double-helix structure.

Production of a mixture of d- and l-sugars produces nucelotides that do not fit together properly, producing a very open, weak structure that cannot survive to replicate, catalyze, or synthesize other biological molecules.

RNA & DNA: It's prebiotic synthesis: Impossible !!  34a10
In DNA the atoms C1', C3', and C4' of the sugar moiety are chiral, while in RNA the presence of an additional OH group renders also C2' of the ribose chiral

RNA & DNA: It's prebiotic synthesis: Impossible !!  3412
A biological system exclusively uses d-ribose, whereas abiotic experiments synthesize both right- and lefthanded-ribose in equal amounts. But the pre-biological building blocks of life didn’t exhibit such an overwhelming bias. Some were left-handed and some right. So how did right-handed RNA emerge from a mix of molecules? 

Some kind of symmetry-breaking process leading to enantioenriched biomonomers would have had to exist. But none is known. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  3112
Gerald Joyce wrote a science paper which was published in Nature magazine, in 1984. His findings, published in Nature in 1984, suggested that in order for life to emerge, something first had to crack the symmetry between left-handed and right-handed molecules, an event biochemists call “breaking the mirror.”

Since then, scientists have largely focused their search for the origin of life’s handedness in the prebiotic worlds of physics and chemistry, not biology - but with no success. So what is the cop-out ? 

RNA & DNA: It's prebiotic synthesis: Impossible !!  3911
Pure chance !! Luck did the job. That is the only thinkable explanation. How could that be a satisfying answer in face of the immense odds? 

RNA & DNA: It's prebiotic synthesis: Impossible !!  4011
But then, the same author, Christian de Duve, Nobel prize winner in physiology or medicine, dismisses instant creation as " heuristically sterile". A sterile discovery ?? in other words, a discovery lacking evidence? 

RNA & DNA: It's prebiotic synthesis: Impossible !!  4111
In his following book, Genetics of Original Sin, he then extended a bit further, and exposed what he meant by "heuristically sterile". 

 RNA & DNA: It's prebiotic synthesis: Impossible !!  4212
It is conceivable that the molecules were short enough for all possible sequences, or almost, to be realized (by way of their genes) and submitted to natural selection. So, this is the way de Duve thought that Intelligent Design could be dismissed. This coming from a Nobel prize winner in medicine is nothing short than shocking, to say the least. 

De Duve dismissed intelligent design and replaced it with natural selection. Without providing a shred of evidence. But based on pure guesswork and speculation.



Last edited by Otangelo on Mon Jun 21, 2021 9:00 am; edited 7 times in total

https://reasonandscience.catsboard.com

4RNA & DNA: It's prebiotic synthesis: Impossible !!  Empty Main points addressed in the video Sat Jun 15, 2019 1:17 pm

Otangelo


Admin

1b. Selecting the right backbone ribose sugar
RNA & DNA: It's prebiotic synthesis: Impossible !!  2k10

Another interesting observation is that RNA and DNA use a five-membered ribose ring structure as a backbone element. It is found that six-membered ring with backbones containing six carbons per sugar unit instead of five carbons and six-membered pyranose rings instead of five-membered furanose rings do not possess the capability of efficient informational Watson–Crick base-pairing. 

Therefore, these systems could not have acted as functional competitors of RNA of a genetic system, even though these six-carbon alternatives of RNA should have had a comparable chance of being formed under the conditions that formed RNA. The reason for their failure revealed itself in chemical model studies: six-carbon-six-membered-ring sugars are found to be too bulky to adapt to the requirements of Watson–Crick base-pairing within oligonucleotide duplexes.

In sharp contrast, an entire family of nucleic acid alternatives in which each member comprises repeating units of one of the four possible five-carbon sugars (ribose being one of them) turns out to be highly efficient informational base-pairing system.

RNA & DNA: It's prebiotic synthesis: Impossible !!  2l10

But why and how would natural unguided events on early earth select what works? Observe the authors end note of above science paper: Optimization, not maximization, of base-pairing strength, was a determinant of RNA's selection. But why would unguided events select something, that by its own has no function? The five-membered furanose or six-membered pyranose ring would simply lay around and then disintegrate without any function whatsoever. 

The smuggling in of evolutionary jargon is evident, and so the fact that the authors do omit these relevant questions that should be asked in order to keep the naturalistic paradigm alive. But its also evident how nonsensical such inferences are. 

1c. Size Complementarity of the nucleotide bases to form a DNA strand
RNA & DNA: It's prebiotic synthesis: Impossible !!  9410
DNA molecules are asymmetrical, such property is essential in the processes of DNA replication and transcription. Above picture demonstrates why bases need to be paired between pyrimidines and purines. In molecular biology, complementarity describes a relationship between two structures each following the lock-and-key principle.

RNA & DNA: It's prebiotic synthesis: Impossible !!  2g10

The formation of the double-helix spiral staircase-like structure, how did it arise? 

RNA & DNA: It's prebiotic synthesis: Impossible !!  2611
Complementarity is the base principle of DNA replication and transcription as it is a property shared between two DNA or RNA sequences, such that when they are aligned antiparallel to each other, the nucleotide bases at each position in the sequences will be complementary, much like looking in the mirror and seeing the reverse of things. This complementary base pairing is essential for cells to copy information from one generation to another.






RNA & DNA: It's prebiotic synthesis: Impossible !!  9510
There is no reason why these structures could or would have emerged in this functional complex configuration by random trial and error processes. Above paper from Nature magazine, from 2016, demonstrates the complete lack of explanations despite of decades of attempts to solve the riddle. 

2. Bringing all the parts together and joining them in the right position

RNA & DNA: It's prebiotic synthesis: Impossible !!  5211
  
Once all the parts would have been available, they would have had to be joined together to the same assembly site,  and sorted out from non-functional molecules.  Joining all three components together involves two difficult reactions: formation of a glycosidic bond, with the right stereochemistry linking the nucleobase and ribose, and phosphorylation of the resulting nucleoside.



RNA & DNA: It's prebiotic synthesis: Impossible !!  5510
In order a molecule to be a self-replicator, it has to be a homopolymer, of which the backbone must have the same repetitive units; they must be identical. On the prebiotic world, for what reason would the generation of a homopolymer be useful? Consider that only random unguided events could account for the generation, which seems rationally extremely unlikely, if not impossible. The chance for that alone occurring randomly is extremely remote

2a. Glycosidic bond formation between nucleosides and the base
RNA & DNA: It's prebiotic synthesis: Impossible !!  6011
Whatever the mode of joining base and sugar was, it had to be between the correct nitrogen atom of the base and the correct carbon atom of the sugar.

The prebiotic synthesis of simple RNA molecules would, therefore, require an inventory of ribose and the nucleobases. Assembly of these components into proto-RNA would further require a mechanism to link the ribose and nucleobase together in  the proper configuration to form polymers, 

and then to activate the combined molecule (called a nucleoside) with a pyrophosphate or some other functional component that would promote formation of a bond between the nucleoside and the growing polymer.

Nucleosides are formed by linking an organic base ( guanine, adenine, uracil or cytosine) to a sugar (here D-ribose). This reaction looks simple, but how it could have occurred by an enzyme-free prebiotic synthesis, in particular involving pyrimidine bases, is an open question. There have been many imaginative ideas and attempts for its solution, all unsuccessful.  

In most cases the nucleoside components generated in the experiments, attempting to join the bases to the Ribose backbone represent only a minor fraction of a full suite of compounds produced, so that synthesis of a nucleoside would require either that the components be further purified or that some mechanism exist to selectively bring the components together out of a complex mixture.

How would non-guided random events be able to attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place?  The coupling of ribose with a base is the first step to form RNA, and even those engrossed in prebiotic research have difficulty envisioning that process, especially for purines and pyrimidines.”

The emergence and existence of catalytic polymers are fundamental. Postulates of how polymerisation could have occurred on prebiotic earth are, therefore, another essential question that has not been elucidated.

RNA & DNA: It's prebiotic synthesis: Impossible !!  3611

There are no known ways of bringing about this thermodynamically uphill reaction in aqueous solution: purine nucleosides have been made by dry-phase synthesis, but not even this method has been successful for condensing pyrimidine bases and ribose to give nucleosides.

Laboratory-based chemical syntheses of ribonucleotides do most, if not all, require manipulation of sugars and nucleobases with protecting group strategies to overcome the thermodynamic and kinetic pitfalls that prevent their fusion. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  8110
In a research paper from 2010, John D. Sutherland reported: Under plausible prebiotic conditions, condensation of nucleobases with ribose to give β-ribonucleosides is fraught with difficulties. The reaction with purine nucleobases is low-yielding and the reaction with the canonical pyrimidine nucleobases does not work at all.  Fitting the new synthesis to a plausible geochemical scenario is a remaining challenge.

2b. The prebiotic phosphodiester bond formation problem

RNA & DNA: It's prebiotic synthesis: Impossible !!  1912
Another major problem that origin of life research faces is how to explain the transition from monomer ribonucleotides to polynucleotides. Phosphodiester bonds are central to all life on Earth as they make up the backbone of the strands of nucleic acid. 

In DNA and RNA, the phosphodiester bond is the linkage between the 3' prime carbon atom of one sugar molecule and the 5' prime carbon atom of another, deoxyribose in DNA and ribose in RNA.

In modern cells, in order for the phosphodiester bond to be formed and the nucleotides to be joined, the tri-phosphate or di-phosphate forms of the nucleotide building blocks are broken apart to give off energy required to drive the enzyme-catalyzed reaction.

Once a single phosphate or two phosphates (pyrophosphates) break apart and participate in a catalytic reaction, the phosphodiester bond is formed.

The general problem regarding the condensation of small organic molecules to form macromolecules in an aqueous environment is the thermodynamically unfavorable process of water removal. In the current biosphere, these types of reactions are catalyzed by enzymes and energetically driven by pyrophosphate hydrolysis.

Obviously, biocatalysts and energy-rich inorganic phosphorus species were not extant on the Earth before life began. In all cases, the starting problem in a prebiotic synthesis would be the fact that materials would consist of an enormous amount of disparate molecules lying around unordered, and would have had to be separated and sorted out.

RNA & DNA: It's prebiotic synthesis: Impossible !!  2911
The intrinsic nature of the phosphodiester bonds is also finely-tuned. For instance, the phosphodiester linkage that bridges the ribose sugar of RNA could involve the 5’ OH of one ribose molecule with either the 2’ OH or 3’ OH of the adjacent ribose molecule. RNA exclusively makes use of 5’ to 3’ bonding. There are no explanations of how the right position could have been selected abiotically in a repeated manner in order to produce functional polynucleotide chains. 

As it turns out, the 5’ to 3’ linkages impart far greater stability to the RNA molecule than does the 5’ to 2’ bonds. Nucleotides can polymerize via condensation reactions.. Ribonucleotides are shown above, but the same reaction occurs between deoxyribonucleotides.

RNA & DNA: It's prebiotic synthesis: Impossible !!  2011
In order a molecule to be a self-replicator, it has to be a homopolymer, of which the backbone must have the same repetitive units; they must be identical. On the prebiotic world, the generation of a homopolymer was however extremely unlikely, if not impossible.

The activated nucleotides (or the nucleotides with coupling agent) now had to be polymerised. Initially, this could not have happened with a pre-existing polynucleotide template.

RNA & DNA: It's prebiotic synthesis: Impossible !!  2ff10

In the case of RNA, not only must phosphodiester links be repeatedly forged, but they must ultimately connect the 5 prime‑oxygen of one nucleotide to the 3 prime‑oxygen, and not the 2 prime‑oxygen, of the next nucleotide. .  

How could and would random events attach a phosphate group to the right position of a ribose molecule to provide the necessary chemical activity? 
 

RNA & DNA: It's prebiotic synthesis: Impossible !!  2fffff11

Above science paper admits: "A fundamental requirement of the RNA world hypothesis is a plausible nonenzymatic polymerisation of ribonucleotides that could occur in the prebiotic environment, but the nature of this process is still an open issue."


In present-day cells, polymerisation is carried out by enzymes with high efficiency and specificity. Enzymes are genetically encoded polymers requiring a complex, protein-based synthetic machinery

Observe what they write at the conclusion: " Selection toward highly efficient catalytic peptides, which eventually resulted in present-day enzymes, could have started at a very early stage of chemical evolution." 


This is an entirely unsupported claim. Readers without training in biochemistry will simply believe it, without further questioning. And that is what goes in basically the entire scientific literature that deals with origins. Nothing besides just so stories based on evolutionary guesswork !!

In living organisms today, adenosine-5'-triphosphate (ATP) is used for activation of nucleoside phosphate groups, but ATP would not be available for prebiotic syntheses. Joyce and Orgel note the possible use of minerals for polymerization reactions, but then express their doubts about this possibility

2c. Fine-tuning of the strength of the hydrogen base pairing forces 

RNA & DNA: It's prebiotic synthesis: Impossible !!  2j10
Hydrogen bond base pairing forces are essential for the mechanisms associated with DNA stability.

[size=12]DNA  has by its own no function. Its purpose is to be used as "letters", storing codified instructional complex information based on their specific sequences arranged in the DNA molecules.[/size]

[size=12]It is sufficiently striking already to know that the universe, its initial conditions, cosmic constants, physical laws, and conditions on earth must be finely tuned for the emergence and flourishing of life.  What is less known however is, that fine-tuning is also extending and required in biochemistry.[/size]

Fine-tuning in biochemistry is represented by the strength of the chemical bonds that makes the universal genetic code possible. Neither transcription nor translation of the messages encoded in RNA and DNA would be possible if the strength of the bonds had different values. Hence, life, as we understand it today, would not have arisen.

As it happens, the average bond energy of a carbon-oxygen double bond is about 30 kilocalories per mol higher than that of a carbon-carbon or carbon-nitrogen double bond, a difference that is life essential. If it were not so, Watson–Crick base-pairing would not exist – nor would the kind of life we know.


3. The instability, degradation, and asphalt problem 
RNA & DNA: It's prebiotic synthesis: Impossible !!  6110
The chemical instability of RNA is explained by the presence of a hydroxyl group in position 2’, which results in an easy strand cleavage through an intramolecular reaction. Such a cleavage is impossible in DNA, where the hydroxyl group at 2’ is absent.


RNA & DNA: It's prebiotic synthesis: Impossible !!  9210

“An enormous amount of empirical data have established, as a rule, that organic systems, given energy and left to themselves, devolve to give uselessly complex mixtures, ‘asphalts’ .” In summary, the asphalt problem, also known as the tar problem, is the typical, expected outcome of prebiotic processes. 

Randomly joined assemblies of random molecules of either covalent or hydrogen bonds should plausibly form random, chaotic mixtures not linear polymers. This has been repeatedly, consistently observed experimentally.

Furthermore, RNA typically degrades in a matter of days and there is no known mechanism to remove the products of degradation from the setting. Eventually, accumulated degradation products should present yet another layer of contamination. 

Natural processes tend to make many more wrong products than usable ones and the ratio is plausibly large enough to prove fatal to abiogenesis.

Stanley L. Miller concluded that the instability of ribose stemming from its carbonyl group “preclude[s] the use of ribose and other sugars as prebiotic reagents. . . . It follows that ribose and other sugars were not components of the first genetic material.”

4. The energy problem


RNA & DNA: It's prebiotic synthesis: Impossible !!  8310
Prebiotic processes are similar in character to dumping a tank of gasoline on a car and igniting it.  By contrast, living cells have machinery which converts energy appearing in a specified form into ATP, the energy currency of the cell, which is useful for biotic processes. 

The form of energy to be converted into ATP varies among cellular types, such as UV light, visible light, methane, metallic ion flow, or digestible nutrients. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  8410
Without machinery matched to the form of energy, energy tends either to have no effect or to act as a tank of gas dumped on a car.

RNA & DNA: It's prebiotic synthesis: Impossible !!  8210
How an ordered energy supply got " off the hook" is a serious enigma and conundrum. It is as if a rock chose a road to roll upwards, 


RNA & DNA: It's prebiotic synthesis: Impossible !!  8510

or a rusty nail "figuring out" how to spontaneously rust and add layers of galvanizing zinc on itself to fight corrosion. 



RNA & DNA: It's prebiotic synthesis: Impossible !!  8611
Unintelligent simple chemicals can't self-organize into instructions for building solar farms (photosystem 1 and 2 in photosynthesis), hydroelectric dams (ATP synthase), propulsion (motor proteins) , self repair (p53 tumor suppressor proteins) or self-destruct (caspases) in the event that these instructions become too damaged by the way the universe USUALLY operates.


 Abiogenesis is not an issue that scientists simply need more time to figure out but a fundamental problem with materialism

5. The minimal nucleotide quantity problem 
RNA & DNA: It's prebiotic synthesis: Impossible !!  8710
The prebiotic conditions would have had to be right for reactions to give perceptible yields of bases that could pair with each other. Even if prebiotic events would have been able to make RNA prebiotically, not only a few nucleotides would have been required, but trillions.  A minimal cell requires a genome of at least 541,000  nucleotides. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  8810
Proposing that unguided random chemical reaction events would have produced trillions of repetitive units of each type of nucleotides, all right sized and complementary to form a double helix structure stretches far beyond what is plausible of what chance can do. Regardless of whether the actual minimum is 100,000  or 500,000 nucleotides, this is far beyond the possible range of a prebiotic nucleic acid generating mechanism.

It would eventually be able to generate a polymer with 200 nucleotides, which however soon would fall apart. Current understanding of information can give many explanations of the difficulties of creating it. It cannot explain where it comes from. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  8910
The prebiotic appearance of nucleotides and long polymers is more difficult than the appearance of amino acids and proteins. Hence, it should take longer than 10^100.000  years to for the appearance of a gene with 780 nucleotides able to code for a specifically required protein. Yet, a 200  ribonucleic acid degrades in a matter of days.

It is implausible that a googol of googol years would be enough time. On a practical basis this discussion is nonsense. These numbers are so extreme that the human mind cannot comprehend their significance.

What is required here is not some wild one-off freak of an event: it is not true to say ‘it only had to happen once’. Trillions of attempts would have had to occur to start the role of  RNA's both, as a catalyst and informational carrier.
Prebiotic processes inherently function as random product generators, producing non-functional random substrates.

6. The Water Paradox 
Water is commonly viewed as essential for life, and theories of water are well known to support this as a requirement. So are RNA, DNA, and proteins. However, these biopolymers are corroded by water. For example, the hydrolytic deamination of DNA and RNA nucleobases is rapid and irreversible, as is the base-catalyzed cleavage of RNA in water.

This leads to a paradox: RNA requires water to do its job, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place. There are no solutions in sight to solve this paradox; life needs water that is inherently toxic to RNA necessary for life.

7. The transition problem from prebiotic to biochemical synthesis
Even if all this in a freaky accident occurred by random events, that still says nothing about the huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network and information system, where complex biosynthesis pathways produce nucleotides and all basic building blocks in modern cells. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  413
The huge gap cannot be outlined enough, leading straight to the famous chicken & egg situation. Chicken and egg scenarios in cellular function can be discovered at will. The essential components of a minimal cell cooperate with each other, such that when all work together life appears and missing any one of them prevents its appearance.

The gap between prebiotic chemistry and biochemistry is one of the biggest problems of abiogenesis research.  Prebiotic chemistry does not resemble extant biochemistry in terms of substrates, reaction pathways, catalysts or energy coupling.


The difficult condensation reactions to form nucleotides and polymers including RNA, DNA and polypeptides are accomplished in water, using energy in the form of ATP. None of this bears any resemblance to prebiotic chemistry proposals.

The difficulty is extrapolating backwards from the supposed so-called last universal common ancestor (LUCA) to prebiotic chemistry. LUCA certainly had genes and proteins, and that level of complexity is undeniably a long way from prebiotic chemistry.


RNA & DNA: It's prebiotic synthesis: Impossible !!  6410
How could chemical evolution define a proper genetic structure to instruct the make of a protein so that the protein could provide a step in the production of an essential product before all of the other proteins required in the biosynthesis pathway had appeared? There is a long list of products essential to the appearance of the first cell. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  6710
Biological systems work as factories or machines. Cells host a big number of the most various molecular machines equal to factory production lines. DNA is trascribed to RNA, which is translated into proteins. But proteins are required to make DNA and RNA. This creates an endless loop, which is only solved when we posit that all three were created at the same time. 


Pick any one of the products, and try to explain how this product could appear apart from single-step, the sudden first appearance of all enzymes and proteins required in the production-line-like metabolic process, where several proteins work in a joint venture in a holistic manner to produce all basic building blocks, essential for life?

RNA & DNA: It's prebiotic synthesis: Impossible !!  6810
The scenarios of prebiotic production of the basic building blocks of life are far distant from the extremely complex metabolic pathways used in even the smallest known cells, like mycoplasma genitalum. The pathway to make pyrimidines, namely cytosine and uracil which yields RNA, and the further transformation of uracil to thymine, the base used in DNA, is extremely complex.

RNA & DNA: It's prebiotic synthesis: Impossible !!  6910
The pathway to make purines is even more complex, as can be seen in the picture above.  The pathway consists of 11 enzymatic steps.

RNA & DNA: It's prebiotic synthesis: Impossible !!  7010
The transition from RNA to DNA is extremely complex, and one enzyme deserves to be mentioned in special: Ribonucleotide Reductase. which converts Ribonucleotides to Deoxyribonucleotides used in DNA. 

Ribonucleotide Reductase are essential enzymes to sustain life in all free-living cells, providing the only known de novo pathway for the biosynthesis of deoxyribonucleotides, the immediate precursors for DNA synthesis and repair.

Consider that the making of DNA and all these extremely complex enzymes had to emerge prior when life began and without evolution. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  7110
And that brings us again to the catch-22 situation as mentioned before:

RNA & DNA: It's prebiotic synthesis: Impossible !!  7210
essential basically means, irreducible....

RNA & DNA: It's prebiotic synthesis: Impossible !!  9010
This exposure here had not dealt with the problem of information, the fact that self-replication would only have been possible after the Eigen treshold would have been reached, and the fact that the make of proteins is an irreducibly complex process, involving besides DNA and RNA many other ingredients, as listed above. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  9110

Unguided prebiotic synthesis of RNA and DNA: an unsolved riddle!

One of the more enigmatic and difficult problems confronting the prebiotic chemistry community is identifying how the monomers of RNA, or pre-RNA, or even non-related polymeric components selectively formed and self-assembled out of the presumed random prebiotic mixtures. 


It is in this assembly into informational polymers  where significant selection processes must have occurred not only for the base composition but also for the other components of nucleic acids (or nucleic acid alternatives and precursors). 

Nucleotide metabolism is central to all biological systems, due to their essential role in genetic information and energy transfer, which in turn suggests its possible presence in the supposed last universal common ancestor (LUCA) from which all life forms originate, that is  Bacteria, Archaea and Eukaryotic cells.

RNA & DNA: It's prebiotic synthesis: Impossible !!  3810
A vast number of books and scientific literature exists on this subject.  For several decades, the best chemists in the world have vigorously addressed the problem of the prebiotic synthesis of RNA. Their efforts however determined and imaginative their approaches, have not been encouraging.

RNA & DNA: It's prebiotic synthesis: Impossible !!  2ffggg10
First of all, the origin of the RNA and DNA molecule is an origin of life problem, not evolution. Evolution depends on DNA replication, therefore, DNA must have preceded evolution. And therefore, its origin cannot be explained by evolutionary mechanisms. DNA  had to emerge together with the machinery of replication and transcription as a pre-requisite for kick-starting life. 

 The supposed abiotic synthesis of RNA and thus the abiotic assembly of its components, including nucleobases, as precursors, is, therefore, a central issue in understanding the origins of life. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  2eeeee10
This observation is highly relevant because it outlines that the origin of ribonucleotides, the building blocks of DNA, could not have emerged prior to life started, but are a pre-requisite.

 The above paper confirms this when they write: The highly conserved ribonucleotide biosynthetic pathway very likely appeared prior to the divergence of the three major lineages.  

RNA and ribonucleotides are ubiquitous and play key catalytic, structural and regulatory roles in biological processes. It is remarkable how the authors then proceed by making several claims, and inferences which are a non-sequitur based on the evidence at hand. Also, when they claim that polyribonucleotides interacted with other compounds. 

Well, before even starting about interactions of what polyribonucleotides supposedly did, it has to be explained how they came to be, which the authors confess:

 We still do not know how the RNA World first appeared. This is a remarkable admission. But then rather than elucidating why they don't know they move forward with further assertions lacking support entirely, despite they claim otherwise. 

RNA & DNA: It's prebiotic synthesis: Impossible !!  1713

Above is another paper which outlines that RNA and DNA had to be fully setup when life began. The authors write: Thermally stable RNA is restricted to a narrow sequence space that is incompatible with the freedom of sequence information required for an RNA genome. Therefore, LUCA must have exhibited the extant DNA/RNA dichotomy. DNA has a half-life on geologic time scales, while catalytic mRNA has a half-life on metabolic time scales.

RNA & DNA: It's prebiotic synthesis: Impossible !!  2113
This paper is worth mentioning for several reasons. As usual, it starts with the unsupported claim that nucleotides of RNA appear to be products of evolution.

Then, soon after, they admit that the origin of RNA is an open question. The blatant contradiction could not be more evident. In the end, outlined in red, the authors point out that there is a vast chemical space from where the possible molecules had to be separated. 

Again, it is obvious, that there is no reason whatsoever why natural causes without foresight nor goals would start such a selection process.

RNA & DNA: It's prebiotic synthesis: Impossible !!  3011
The book: Biological science admits:
The production of nucleotides remains a serious challenge for the theory of chemical evolution. At this time, experiments that attempt to simulate early Earth environments have yet to synthesize complete nucleotides.

RNA & DNA: It's prebiotic synthesis: Impossible !!  1411
Paul Davies The Algorithmic Origins of Life
Despite the conceptual elegance of the RNA world, the hypothesis faces problems, primarily due to the immense challenge of synthesizing RNA nucleotides under plausible prebiotic conditions and the susceptibility of RNA oligomers to degradation via hydrolysis.



RNA & DNA: It's prebiotic synthesis: Impossible !!  5311
The inevitable conclusion of this survey of nucleotide synthesis is that there is at present no convincing, prebiotic total synthesis of any of the nucleotides.

Many individual steps that might have contributed to the formation of nucleotides on the primitive Earth have been demonstrated, but few of the reactions give high yields of products, and those that do tend to produce complex mixtures of products.

RNA & DNA: It's prebiotic synthesis: Impossible !!  5711

Steve Benner is the founder and president of the Westheimer Corporation, a private research organization, and a prior Harvard University professor. He is one of the world’s leading authorities on abiogenesis. This is his evaluation of what he has observed: We are now 60 years into the modern era of prebiotic chemistry. 

That era has produced tens of thousands of papers attempting to define processes by which “molecules that look like biology” might arise from “molecules that do not look like biology” …. For the most part, these papers report “success” in the sense that those papers define the term…. And yet, the problem remains unsolved

Steven Benner has been remarkably courageous by admitting openly and categorically:  The “origins problem” cannot be solved. Long periods of time do not make life inevitable. Molecules rather disintegrate based on the second law of thermodynamics. and randomization turns more complete.

Since prebiotic processes are natural randomizers and abiogenesis requires specific products, it does not appear that prebiotic processes have inherent capability to meet the requirements necessitated for successful abiogenesis. This plausibly characterizes every hypothetical step of abiogenesis and explains why none have succeeded.  

Claude Shannon showed that randomization is the fundamental behavior and entropy is simply a mathematical expression of certain of its aspects

RNA & DNA: It's prebiotic synthesis: Impossible !!  6310
2017, english Chemist John Sutherland formed nucleotides, amongst all of the basic building blocks—lipids for compartments, amino acids for metabolism, starting with cyanide as a common initial substrate.

 However, this ended up requiring six separate ponds with their own unique geochemical conditions and whose products then needed to be mixed together in a specific sequence.

Even this degree of complexity did not supply required products, but only precursors.  The requirement of so many unique ponds and associated chemistries in such close proximity to each other, of coure, stretches plausibility.


RNA & DNA: It's prebiotic synthesis: Impossible !!  9310
I think, to say that on average the 14 hurdles that it would take to make primed nucleotides would each take 10 unit operations - that at least 140 little events would have to be appropriately sequenced. Unguided, the appropriate thing happened at each point on one occasion in six. 

The odds against a successful unguided synthesis of a batch of primed nucleotide on the primitive Earth would be a huge number, represented approximately by a 1 followed by 109 zeros ( 10^109).

How did Nature start to play this game? At the very least a maintained supply of primed nucleotides would be required for any kind of organism using our kind of message tapes. A nucleotide making factory would be needed.
 
'The odds are enormous against its being coincidence. No figures could express them.'



Last edited by Otangelo on Mon Jun 21, 2021 7:49 am; edited 2 times in total

https://reasonandscience.catsboard.com

5RNA & DNA: It's prebiotic synthesis: Impossible !!  Empty The problem of making Ribose prebiotically Mon Mar 23, 2020 11:14 am

Otangelo


Admin

What is Benner's solution to explain how the right-handedness of ribose was selected amongst a mixed pool of enantiomeric right and left-handed ribose? In life, only right-handed ribose is viable, and biological systems exclusively use d-ribose, whereas abiotic experiments synthesize both right- and lefthanded-ribose in equal amounts. But the pre-biological building blocks of life didn’t exhibit such an overwhelming bias. Some were left-handed and some right. So how did right-handed RNA emerge from a mix of molecules?

Some kind of symmetry-breaking process leading to enantioenriched biomonomers would have had to exist. But none is known.

You resort to Benner's YouTube videos. Shall we see what he says about this issue?

https://www.youtube.com/watch?v=v5HQB3JFIZg
We've not said a word about chirality here and that's a big problem
That's all. What else did he say about it? Nothing.

RNA and DNA use a five-membered ribose ring structure as a backbone element. It is found that six-membered ring with backbones containing six carbons per sugar unit instead of five carbons and six-membered pyranose rings instead of five-membered furanose rings do not possess the capability of efficient informational Watson–Crick base-pairing.

Therefore, these systems could not have acted as functional competitors of RNA of a genetic system, even though these six-carbon alternatives of RNA should have had a comparable chance of being formed under the conditions that formed RNA. The reason for their failure revealed itself in chemical model studies: six-carbon-six-membered-ring sugars are found to be too bulky to adapt to the requirements of Watson–Crick base-pairing within oligonucleotide duplexes.

In sharp contrast, an entire family of nucleic acid alternatives in which each member comprises repeating units of one of the four possible five-carbon sugars (ribose being one of them) turns out to be highly efficient informational base-pairing system.

Stanley L. Miller concluded that the instability of ribose stemming from its carbonyl group “preclude[s] the use of ribose and other sugars as prebiotic reagents. . . . It follows that ribose and other sugars were not components of the first genetic material.”

As Shapiro has pointed out, the formose reaction which makes ribose  will not produce sugars in the presence of nitrogenous substances. These include peptides, amino acids, and amines, a category of molecules that includes the nucleotide bases. This obviously poses difficulties. First, it creates a dilemma for scenarios that envision proteins and nucleic acids arising out of a prebiotic soup rich in amino acids. Either the prebiotic environment contained amino acids, which would have prevented sugars (and thus DNA and RNA) from forming, or the prebiotic soup contained no amino acids, making protein synthesis impossible. Of course, RNA-first advocates might try to circumvent this difficulty by proposing that proteins arose well after RNA. Yet since the RNA-world hypothesis envisions RNA molecules coming into contact with amino acids early on within the first protocellular membranes, choreographing the origin of RNA and amino acids to ensure that the two events occur separately becomes a considerable problem.

James Tour:
“The coupling of a ribose with a nucleotide is the first step [in abiogenesis], and even those engrossed in prebiotic research have difficulty envisioning that process, especially for purines and pyrimidines.”

A further problem lies in the synthesis and preservation of ribose, with the right chirality. ribose is not particularly preferred over other sugars nor is it stable. Hence, an autocatalytic cycle designed to produce large amounts of carbohydrates from formaldehyde will not preferentially make ribose nor preserve it. One then faces the question of how ribose molecules were maintained against chemical processes that tend to decompose them quickly into a nondescript assemblage of polymeric mixtures. The ribose produced must have the correct handedness or chirality; on Earth, d-sugars are exclusively involved in living processes. Production of a mixture of d- and l-sugars produces nucelotides that do not fit together properly, producing a very open, weak structure that cannot survive to replicate, catalyze, or synthesize other biological molecules. In fact, the synthesis of the RNA molecule itself is interrupted by mixing nucleotides of different chirality; only in a controlled laboratory experiment or theoretical model can such an assemblage be realized.
To create a properly functioning RNA molecule out of a batch of heterochiral l- and d-sugars is a daunting challenge. The genetic template that sustains a particular kind of chemistry and set of structures is quickly lost after just one generation.

Has Benner solved all these issues? No.
Has any other scientist solved these issues? No.
Can we conclude that these issues will not be solved? Yes. The evidence points to this direction.

https://reasonandscience.catsboard.com

Otangelo


Admin

Purine base synthesis, by design, or non-design?

Purines are one of the two nucleobases used to make RNA and DNA. ( The others are pyrimidines). Since RNA and DNA are life-essential, the transition from prebiotic non-enzymatic, to their enzymatic synthesis had to emerge prior to the first self-replicating cells were existing. So neither evolution nor natural selection can be resorted to, to explain its origin. 

Anthony M. Pedley: A New View into the Regulation of Purine Metabolism – The Purinosome 2018 Feb 1

The de novo purine biosynthetic pathway is a highly conserved, energy-intensive pathway. In humans, this metabolic transformation is carried out in ten steps by sequential orchestration of six enzymes. The six enzymes also rely on numerous amino acid substrates and cofactors. For each molecule of IMP generated, five molecules of ATP, two molecules each of glutamine and formate, and one molecule each of glycine, aspartate, and carbon dioxide are needed. Glutamine and aspartate are generated from intermediates of the tricarboxylic acid cycle.  Formate, a metabolite exported from mitochondria, is required for the biosynthesis of the 10-formyltetrahydrofolate cofactor, which in turn is needed for the transformylase activity of GART.

Purinosome assembly in cells is proposed as a stepwise process. The exact triggers for purinosome formation are not known. Metabolic enzymes organize within the cytosol to form a given network, densely pack with myriad proteins and metabolites, to facilitate metabolic flux. One solution is through the formation of a macromolecular complex of enzymes termed a metabolon. Enzymes in other metabolic pathways such as the tricarboxylic acid cycle and glycolysis have been found to form metabolons and well-orchestrated action of these components holds the key for efficient metabolite synthesis. The resulting microenvironment sequesters reactive intermediates to enhance their stability and avoid interferences by other cellular constituents. The rationale for compartmentalization has largely relied on kinetic arguments. Specifically, the product of the first reaction in the de novo purine biosynthetic pathway, PRA, has a very short solution half-life and may directly transfer to the subsequent enzyme, GART, through complexation of the two enzymes. Similarly, GART catalyzes non-concerted steps within the same pathway and requires the activity of FGAMS for the fourth step raising the possibility that FGAMS interacts with GART.

Question: Had this complexification of two enzymes not happened right from the beginning, would that not have resulted in an error catastrophe? Was the complexification achieved by trial and error?

Behe notes that there is a fundamental quality of any irreducibly complex system in that, "any precursor to an irreducibly complex system that is missing a part is by definition nonfunctional.” Not only have the intermediate metabolites to go through the entire biosynthesis pathway to have a function end product. But the enzymes that operate like autonomous robots have to be all there, in the right order, none of the can be missing. How did that state of affairs emerge?

On the one side you have an intelligent agency-based system of irreducible complexity of tight integrated, information-rich functional systems which have ready on-hand energy directed for such, that routinely generate the sort of phenomenon being observed.  And on the other side imagine a golfer, who has played a golf ball through an 12-hole course. Can you imagine that the ball could also play itself around the course in his absence? Of course, we could not discard, that natural forces, like wind, tornadoes or rains, or storms could produce the same result, given enough time.  the chances against it, however, are so immense, that the suggestion implies that the non-living world had an innate desire to get through the 12-hole course.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5272809/

https://reasonandscience.catsboard.com

7RNA & DNA: It's prebiotic synthesis: Impossible !!  Empty Prebiotic origin of nucleotides Mon Jun 13, 2022 4:42 am

Otangelo


Admin

Prebiotic origin of nucleotides

https://reasonandscience.catsboard.com/t2865-rna-dna-it-s-prebiotic-synthesis-impossible#9320

Nucleotides
DNA (deoxyribonucleic acid) are the molecules that make up the “alphabet” which specifies biological heredity. Life is information-driven. Specified complex information stored in genes dictates, instructs and directs the making of very complex molecular machines, autonomous robotic production lines, and chemical cell production plants, and it also directs and orders the cell to do its work, and how to operate and is as such of central importance in all life forms. Who wants to find answers about how life started, needs to find compelling explanations about how RNA and DNA first emerged on earth. The information stored in DNA is transcribed into RNA ( ribonucleic acid) and finally translated to make proteins. RNA has several other important roles in the cell. Interestingly, some viruses use RNA to store information. 

Nucleic acid research started in 1871, with a small sentence in the essay “Über die chemische Zusammensetzung der Eiterzellen” He characterized this substance as nitrogen-containing and being very rich in phosphorous. The following decades were marked by resolving the molecular structure of the “nuclein”. (“About the chemical composition of pus cells”) by Miescher 31 James Watson and Francis Crick discovered the structure of the DNA  molecule in 1953.  RNA is built of (almost) the same four-letter alphabet as DNA. It is more fragile, and as such, it could also be an information carrier, but less adequate long term. In all known living beings, genetic information flows from DNA to RNA to proteins. The work of  Watson and Crick on the structure of DNA was performed with some access to the X-ray crystallography of Maurice Wilkins and Rosalind Franklin at King's College London.  This information was critical for their further progress. They obtained this information as part of a report by Franklin to the Medical Research Council. Combining all of this work led to the deduction that DNA exists as a double helix. The report was by no means secret, but it put the critical data on the parameters of the helix (base spacing, helical repeat, number of units per turn of the helix, and diameter of the helix) in the hands of two who had contributed none of those data.  With this information, they could begin to build realistic models. The big problem was where to put the purine and pyrimidine bases. Details of the diffraction pattern indicated two strands and indicated that the relatively massive phosphate ribose backbones must be on the outside, leaving the bases in the center of the double helix.

RNA and DNA  are chemically unlikely molecules that are composed of three parts: a nitrogenous base, a  five-carbon sugar (pentose), and phosphate.  DNA uses thymine as a base, and RNA uses uracil. These monomers are joined to form polymers by the phosphate group. In the genome, they form double strands with Watson-Crick base-pairing. 

How did RNA synthesize prebiotically?
In cells, the synthesis of RNA and DNA requires extremely complex energy-demanding, finely adjusted, monitored,  and controlled anabolic pathways. Since they were not extant prebiotically, RNA had to be synthesized spontaneously on early earth by abiotic alternative non-enzymatic pathways.  This is one of the major, among many other unsolved origin of life problems. Krishnamurthy points out that "there has been some common ground on what would be needed for organic synthesis of DNA/RNA (for example, the components of ribose and nucleobases to come from formaldehyde, cyanide and their derivatives) but none of the various approaches has found universal acceptance within the origins of life community at large. 26

Over the last decades, Extraterrestrial sources like meteorites, interplanetary dust particles, hydrothermal vents in the deep ocean, and warm little ponds, a prebiotic soup, have been a few of the proposals. High-energy precursors to produce purines and pyrimidines would have had to be produced in sufficient quantities, and concentrated at a potential building site of the first cells. As we will see, there has to be put an unrealistic demand for lucky accidents, and, de facto, there is no known prebiotic route to this plausibly happening by unguided means.  

An article published in 2014 summarizes the current status quo: The first, and in some ways the most important, problem facing the RNA World is the difficulty of prebiotic synthesis of RNA. This point has been made forcefully by Shapiro and has remained a focal point of the efforts of prebiotic chemists for decades. The ‘traditional’ thinking was that if one could assemble a ribose sugar, a nucleobase, and a phosphate, then a nucleotide could arise through the creation of a glycosidic bond and a phosphodiester bond. If nucleotides were then chemically activated in some form, then they could polymerize into an RNA chain. Each of these synthetic events poses tremendous hurdles for the prebiotic Earth, not to mention the often-invoked critique of the inherent instability of RNA in an aqueous solution. Thus, the issue arises of whether there could have been a single environment in which all these steps took place. Benner has eloquently noted that single-pot reactions of sufficient complexity lead to ‘asphaltization’ (basically, the production of intractable ‘goo’). 2 

Steve Benner (2012): RNA has been called a “prebiotic chemist's nightmare” because of its combination of large size, carbohydrate building blocks, bonds that are thermodynamically unstable in water, and overall intrinsic instability. No experiments have joined together those steps ( to make RNAs) without human intervention. Further, many steps in the model have problems. Some are successful only if reactive compounds are presented in a specific order in large amounts. Failing controlled addition, the result produces complex mixtures that are inauspicious precursors for biology, a situation described as the “asphalt problem”. Many bonds in RNA are thermodynamically unstable with respect to hydrolysis in water, creating a “water problem”. Finally, some bonds in RNA appear to be “impossible” to form under any conditions considered plausible for early Earth. 48

De Duve confesses: "Unless we accept intelligent design, it is clear that the RNA precursors must have arisen spontaneously as a result of existing conditions" 21 - the problem is, - Science is clueless about how nucleotides could have been formed prebiotically.

Lack of natural selection
The idea that nucleotides were readily laying around on the early earth, just waiting to be picked up, and concentrated on the building site of life, was mocked by Leslie Orgel as 'the Molecular Biologist's Dream. This is maybe the most stringent problem of prebiotic nucleotide synthesis: The materials on prebiotic earth were a mess of mixtures of lifeless chemicals, and nothing restricts the possibility of a great diversity of nucleotides with differing sugar moieties. There was no natural selection. Many science papers simply ignore this and resort nonetheless to little magic of selective pressure. It's like from Frankenstein to man. Some patchwork here and there, and chance does the rest and figures things out.  Szostak and colleagues were well aware of the problem. They wrote:

There are many nucleobase variations such as 8-oxo-purine, inosine, and the 2-thio-pyrimidines, as well as sugar variants including arabino-, 2′- deoxyribo-, and threonucleotides. The likely presence of byproducts leads to a significant problem with regard to the emergence of the RNA world, since the initially synthesized oligonucleotides would be expected to be quite heterogeneous in composition. How could such a heterogeneous mixture of oligonucleotides give rise to the relatively homogeneous RNAs that are thought to be required for the evolution of functional RNAs such as ribozymes? 30

So, in 2020, they presented a model, ignoring the fact made by Benner and others, that molecules simply disintegrate and randomize, they proposed that "  many versions of nucleotides merged to form patchwork molecules with bits of both modern RNA and DNA, as well as largely defunct genetic molecules, such as ANAThese chimeras, like the monstrous hybrid lion, eagle and serpent creatures of Greek mythology, may have been the first steps toward today's RNA and DNA." 29 Rather than focussing "on the consequences of coexisting activated arabino- and 2′-deoxy-nucleotides for nonenzymatic template-directed primer extension", the authors need to provide a plausible trajectory for how natural selection pressures provided the separation of non-canonical nucleotides to achieve a homogeneous state of affairs, where only RNA's and DNAs used in life polymerize. Often, the key questions in the mids of the often confusing technical jargon get lost.  

The nucleobases
The nucleobases are key components of RNA and DNA. The bases are divided into purines ( adenine (A) and guanine (G)) and pyrimidines [cytosine (C) and thymine (T) in DNA, and Cytosine (C) and uracil (U) in RNA]. While purines have a double ring structure and nine atoms, purines have a single ring structure with six atoms. The structural difference between these sugars is that ribonucleic acid contains a hydroxyl (-OH) group, whereas deoxyribonucleic acid contains only a hydrogen atom in place of this hydroxyl group.

Purines
Purines are one of the two compounds that are used to make the semantophoretic nucleotides RNA and DNA that store genetic information. Adenine and guanine are made of two nitrogen-containing rings. 

Adenine
One of the earliest experiments attempting to synthesize adenine in prebiotic conditions was made by Oró in 1961, where he presented evidence for the "synthesis of adenine from aqueous solutions of ammonium cyanide at temperatures below 100°." 18 In 1966, P. Ferris and L. E. Orgel pointed out, what the achilles heel was in Oró's experiment: "Adenine was formed in only 0.5% yield in Oro’s experiment; most of the cyanide formed an intractable polymer."19 Evidently, there was no prebiotic natural selection to sort out those bases that could later be used as nucleobases, from those with no function. 

Shapiro pointed out that: Useful yields of adenine cannot be obtained except in the presence of 1.0 M or stronger ammonia. The highest reasonable concentration of ammonia or ammonium ion that can be postulated in oceans and lakes on the primitive earth is about 0.01 M. Orgel  has put forward the following prerequisite for the very first information system: 'its monomeric components must have been abundant components of a prebiotic mixture of organic compounds.' Adenine does not seem to meet this requirement. The instability of adenine on a geological time scale makes its widespread prebiotic accumulation unlikely. Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine plays an essential role in replication in all known living systems today and is prominent in many other aspects of biochemistry. Despite this, a consideration of its intrinsic chemical properties suggests that it did not play these roles at the very start of life. These properties include the low yields in known syntheses of adenine under authentic prebiotic conditions, its susceptibility to hydrolysis and to reaction with a variety of simple electrophiles, and its lack of specificity and strength in hydrogen bonding at the monomer and mixed oligomer level. 14

Elsewhere, Shapiro addressed an eventual extraterrestrial source: The isolation of adenine and guanine from meteorites has been cited as evidence that these substances might have been available as “raw material” on prebiotic Earth (18). However, acid hydrolyses have been needed to release these materials, and the amounts isolated have been low 5

In a recent paper from 2018, Annabelle Biscans mentions other routes investigated: Miyakama et al. suggest that purines have been formed in the atmosphere in the absence of hydrogen cyanide. They reported that guanine could have been generated from a gas mixture (nitrogen, carbon monoxide, and water) after cometary impacts. Also, it has been proposed that adenine was formed in the solar system (outside of Earth) and brought to Earth by meteorites, given the fact that adenine was found in significant quantity in carbonaceous chondrites.

and concludes: Despite great efforts and impressive advancements in the study of nucleoside and nucleotide abiogenesis, further investigation is necessary to explain the gaps in our understanding of the origin of RNA. 20

Guanine
In 1984, Yuasa reported a 0.00017% yield of guanine after electrical discharge experiments. However, it is unknown if the presence of guanine was not simply resulted from a contaminant of the reaction. . S L Miller and colleagues made experiments in 1999, and yield trace amounts of guanine form by the polymerization of ammonium cyanide (0.0007% and 0.0035% depending on temperatures) indicating that guanine could arise in frozen regions of the primitive earth. 22

Abby Vogel Robinson reported in 2010: For scientists attempting to understand how the building blocks of RNA originated on Earth, guanine -- the G in the four-letter code of life -- has proven to be a particular challenge. While the other three bases of RNA -- adenine (A), cytosine (C) and uracil (U) -- could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.

Pyrimidines
Pyrimidine bases are the second of the quartet that makes up DNA that stores genetic information. Uracil ( Thymine in DNA) and cytosine are made of one nitrogen-containing ring. In 2009, Sutherland, and Szostak published a paper on a high-yielding route to activated pyrimidine nucleotides under conditions thought to be prebiotic, claiming to be "an encouraging step toward the greater goal of a plausible prebiotic pathway to RNA and the potential for an RNA world." 27 Robert Shapiro disagrees:

Although as an exercise in chemistry this represents some very elegant work, this has nothing to do with the origin of life on Earth whatsoever.  The chances that blind, undirected, inanimate chemistry would go out of its way in multiple steps and use of reagents in just the right sequence to form RNA is highly unlikely. 28

Cytosine
Scientists have failed to produce cytosine in spark-discharge experiments.

Robert Shapiro (1999): The formation of a substance in an electric spark discharge conducted in a simulated early atmosphere has also been regarded as a positive indication of its prebiotic availability. Again, low yields of adenine and guanine have been reported in such reactions, but no cytosine. The failure to isolate even traces of cytosine in these procedures signals the presence of some problem with its synthesis and/or stability. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.  12

Rich Deem (2001):  
Cytosine has never been found in any meteorites.
Cytosine is not produced in electric spark discharge experiments using simulated "early earth atmosphere."
Synthesis based upon cyanoacetylene requires the presence of large amounts of methane and nitrogen, however, it is unlikely that significant amounts of methane were present at the time life originated.
Synthesis based upon cyanate is problematical, since it requires concentrations in excess of 1 M (molar). When concentrations of 0.1 M (still unrealistically high) are used, no cytosine is produced.
Synthesis based upon cyanoacetaldehyde and urea suffers from the problem of deamination of the cytosine in the presence of high concentrations of urea (low concentrations produce no cytosine). In addition, cyanoacetaldehyde is reactive with a number of prebiotic chemicals, so would never attain reasonable concentrations for the reaction to occur. Even without the presence of other chemicals, cyanoacetaldehyde has a half-life of only 31 years in water.
Cytosine deaminates with an estimated half-life of 340 years, so would not be expected to accumulate over time.
Ultraviolet light on the early earth would quickly convert cytosine to its photohydrate and cyclobutane photodimers (which rapidly deaminate). 49

Uracil
In 1961, Sidney Fox and colleagues synthesized Uracil under: "thermal conditions which yield other materials of theoretical prebiochemical significance. The conditions studied in the synthesis of uracil included temperatures in the range of 100° to 140°C, heating periods of from 15 minutes to 2 hours". 33  Other attempts to provide plausible prebiotic scenarios for the non-enzymatic synthesis of nucleotides and nucleobases continue to the present day. In 2019, Okamura and colleagues published a paper on pyrimidine nucleobase synthesis where their conclusion remarks is noteworthy:

We show that the cascade reaction proceeds under one-pot conditions in a continuous manner to provide SMePy 6. Importantly the key intermediate SMePy 6 gives rise not only to canonical but also to non-canonical bases arguing for the simultaneous prebiotic formation of a diverse set of pyrimidines under prebiotically plausible conditions.

This highlights a general problem mentioned before: chemical reactions are very common resulting in a mixture of molecules, of which most are not relevant for abiogenesis. There was no mechanism to sort out those detrimental in the process towards life. 32

Fast decomposition rate
Adenine deaminates at 37°C with a half-life of 80 years (half-life = time that a substance takes to decompose, and loses half of its physiologic activity). At 100°C its half-live is 1 year. For guanine, at 100°C its half-live is 10 months, uracil is 12 years, and thymine 56 years.  For the decomposition of a nucleobase, this is very short. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition. Therefore, adenine and the other nucleobases would never accumulate in any kind of "prebiotic soup." 14

A paper published in 2015 points out that: 

Nucleotide formation and stability are sensitive to temperature. Phosphorylation of nucleosides in the laboratory is slower at low temperatures, taking a few weeks at 65 ◦C compared with a couple of hours at 100 ◦C (39). The stability of nucleotides, on the other hand, is favored in warm conditions over high temperatures (40). If a WLP is too hot (>80 ◦C), any newly formed nucleotides within it will hydrolyze in several days to a few years (40). At temperatures of 5 ◦C to 35 ◦C that either characterize more-temperate latitudes or a post snowball Earth, nucleotides can survive for thousand-to-million-year timescales. However, at such temperatures, nucleotide formation would be very slow.  25

That means, in hot environments, nucleotides might form, but they decompose fast. On the other hand, in cold environments, they might not degrade that fast, but take a long time to form. Nucleotides would have to be generated by prebiotic environmental synthesis processes at a far higher rate than they are decomposed and destroyed, and accumulated and concentrated at one specific construction site. Putting that into perspective, P.Ubique, the smallest known free-living cell, has a genome size of 1,3 million nucleotides. The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized in ribose synthesis via the formose reaction, which reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons. There would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.

Nucleotide biosynthesis regulation
Rani Gupta explains:  

Nucleotide biosynthesis is regulated by feedback inhibition, feed-forward activation as well as by cross-regulation. Nucleotide analogs, precursor/substrate analogs and inhibitors of folic acid pathway can inhibit nucleotide biosynthesis. [url=https://link.springer.com/chapter/10.1007/978-981-16-0723-3_19#:~:text=other pyrimidine nucleotides.-,Nucleotide biosynthesis is regulated by feedback inhibition%2C feed%2Dforward activation,pathway can inhibit nucleotide biosynthesis.]15[/url]

Since biosynthesis regulation had to be extant at LUCA, researchers have to explain the emergence of all these complex feedback systems before life started without invoking natural selection & evolution. Instantiating systems that can monitor, fine-tune and regulate complicated production systems is a major challenging task depending on the knowledge and pre-set and foresight of specific targets, and what is intended to be achieved.  

Srivatsan Raman gives us an idea about the process in his paper: Evolution-guided optimization of biosynthetic pathways. He writes:

Microbes can be made to produce industrially valuable chemicals in high quantities by engineering their central metabolic pathways. Through iterations of genetic diversification and selection, we increased the production of naringenin and glucaric acid 36- and 22-fold, respectively. Engineering biosynthetic pathways for chemical production requires extensive optimization of the host cellular metabolic machinery. Because it is challenging to specify a priori an optimal design, metabolic engineers often need to construct and evaluate a large number of variants of the pathway. We report a general strategy that combines targeted genome-wide mutagenesis to generate pathway variants with evolution to enrich for rare high producers.  Because artificial selection tends to amplify unproductive cheaters, we devised a negative selection scheme to eliminate cheaters while preserving library diversity. 16

Engineering, selecting, optimizing, specifying an optimal design, evaluating, elaborating strategies, goal-oriented elimination and preservation and identifying, are all clear activities that require mental elaboration, and are best assigned to an intelligent setup. Daniel Charlier's scientific paper about the crossroad of arginine and pyrimidine biosynthesis in E.Coli bacteria gives us insight into how cells tackle this task: He writes:

In all organisms, carbamoylphosphate (CP) ( which is the second intermediate product in pyrimidine synthesis ) is a precursor common to the synthesis of arginine and pyrimidines. In Escherichia coli and most other Gram-negative bacteria, CP is produced by a single enzyme, carbamoylphosphate synthase (CPSase). This particular situation poses a question of basic physiological interest: what are the metabolic controls coordinating the synthesis and distribution of this high-energy substance in view of the needs of both pathways? The study of the mechanisms has revealed unexpected moonlighting gene regulatory activities of enzymes and functional links between mechanisms as diverse as gene regulation and site-specific DNA recombination. At the level of enzyme production, various regulatory mechanisms were found to cooperate in a particularly intricate transcriptional control of a pair of tandem promoters. Transcription initiation is modulated by an interplay of several allosteric DNA-binding transcription factors using effector molecules from three different pathways (arginine, pyrimidines, purines), nucleoid-associated factors (NAPs), trigger enzymes (enzymes with a second unlinked gene regulatory function), DNA remodeling (bending and wrapping), UTP-dependent reiterative transcription initiation, and stringent control by the alarmone ppGpp. At the enzyme level, CPSase activity is tightly controlled by allosteric effectors originating from different pathways: an inhibitor (UMP) and two activators (ornithine and IMP) that antagonize the inhibitory effect of UMP. Furthermore, it is worth noticing that all reaction intermediates in the production of CP are extremely reactive and unstable, and protected by tunneling through a 96 Å long internal channel. 17

The instantiation of complex network systems that autonomously coordinate, regulate, cooperate, modulate, remodel, control, and protect ( which are all processes to achieve specific results ), require careful planning and engineering skills in order to be instantiated.  In the list of ten things that can be safely attributed as signatures of intelligent setup & design are artifacts which use might be employed in different systems. In the above case, it is one metabolic network, that is used to manufacture different end-products, all needed in the overarching function of the system.

Extraterrestrial nucleobase sources
In april 2022, nature magazine announced the identification of nucleobases in carbonaceous meteorites.  Guanine and adenine were detected in murchison meteorite extracts, and now various pyrimidine nucleobases such as cytosine, uracil, and thymine, and their structural isomers such as isocytosine, imidazole-4-carboxylic acid, and 6-methyluracil, respectively. They came to the conclusion that "a diversity of meteoritic nucleobases could serve as building blocks of DNA and RNA on the early Earth".23 An article of NASA echoed the authors conclusion: "This discovery demonstrates that these genetic parts are available for delivery and could have contributed to the development of the instructional molecules on early Earth."24 The fatal blow is the fact that the nucleobases relevant for life come always mixed together with isomers that are irrelevant. There was no prebiotic selection to sort out and concentrate exclusively those relevant for life. 

Ribose
Pentose sugar is a 5-carbon monosaccharide. These form two groups: aldopentoses and ketopentoses. The pentose sugars found in nucleotides are aldopentoses. Deoxyribose and ribose are two of these sugars.  Ribose is a monosaccharide containing five carbon atoms. d-ribose is present in the six different forms. 

S.Islam explains: The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized for ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons. The reality of the formose reaction is that it descends into an inextricable mixture. The vast array of sugars produced is overwhelming and the intrinsic lack of selectivity for ribose is its undoing. Ultimately, the formose reaction produces a disastrously complex mixture of linear and branched Aldo and keto-sugars in the racemic forms. The consequences of such uncontrolled reactivity are that ribose is formed in less than 1% yield among a plethora of isomers and homologs. The instability of ribose prevents its accumulation and requires it to undergo extremely rapid onward conversion to ribonucleosides before the free sugar is lost to rapid degradation. 36

Irina V Delidovich and colleagues wrote in 2014: The classical formose reaction (FR) is hardly applicable for any practical purposes outside of the history of chemical science. The typical “sugary substance” formed as a result of the catalytic oligomerization of formaldehyde nowadays known as “formose” comprises dozens of straight-chain and branched monosaccharides, polyols, and polyhydroxycarbonic acids.5 There are no further alternatives: Either chance "choose" by fortuitous random events the five-membered ring ribofuranose backbone for DNA and RNA, or it was a choice by intelligence with specific purposes. What is more plausible and probable?  The formose reaction requires a high concentration of Formaldehyde, which, however, readily undergoes a variety of reactions in aqueous solutions. Another problem is that ribose is unstable and rapidly decomposes even at low temperature and neutral pH, and as well in water. Furthermore, as Stanley Miller and his colleagues reported:  Ribose and other sugars have surprisingly short half-lives for decomposition at neutral pH, making it very unlikely that sugars were available as prebiotic reagents. 4

Leslie Orgel (2004): We conclude that some progress has been made in the search for an efficient and specific prebiotic synthesis of ribose and its phosphates. However, in every scenario, there are still a number of obstacles to the completion of a synthesis that yields significant amounts of sufficiently pure ribose in a form that could readily be incorporated into nucleotides. 34

There have been a wide variety of attempts and proposals to try to solve the riddle, but up to date, without success. Science magazine (2016): Ribose is the central molecular subunit in RNA, but the prebiotic origin of ribose remains unknown. 35

Annabelle Biscans (2018): Even if some progress has been made to understand ribose formation under prebiotic conditions, each suggested route presents obstacles, limiting ribose yield and purity necessary to form nucleotides. A selective pathway has yet to be elucidated. 6

RNA and DNA use a five-membered ribose ring structure as backbone. Rings containing six carbons instead of five carbons do not possess the capability of efficient informational Watson–Crick base-pairing. Therefore, these systems could not have acted as functional competitors of RNA in a genetic system, even though these six-carbon alternatives of RNA should have had a comparable chance of being formed under the conditions that formed RNA. The reason for their failure is the fact that six-carbon-six-membered-ring sugars are too bulky to adapt to the requirements of Watson–Crick base-pairing within oligonucleotide duplexes. In sharp contrast, an entire family of nucleic acid alternatives in which each member comprises repeating units of one of the four possible five-carbon sugars (ribose being one of them) turns out to be a highly efficient informational base-pairing system. But why and how would natural non-designed events on early earth select what works? Observe Albert Eschenmoser's end note in his science paper from 1986: Optimization, not maximization, of base-pairing strength, was a determinant of RNA's selection. [url=https://www.science.org/doi/10.1126/science.284.5423.2118#:~:text=Chemical etiology (2) of nucleic,the molecular basis of life's]8[/url] But how and why would unintended events select something, that on its own has no function? These ring structures would simply lay around and then soon disintegrate. The smuggling in of evolutionary jargon is widespread for sake of the lack of any alternative. The authors omit and do not ask these relevant questions. That permits keeping the naturalistic paradigm alive. But it should be evident how nonsensical evolutionary claims and such inferences are. 

Right-handedness of ribose
Tan, Change; Stadler, Rob. The Stairway To Life:
In all living systems, homochirality is produced and maintained by enzymes, which are themselves composed of homochiral amino acids that were specified through homochiral DNA and produced via homochiral messenger RNA, homochiral ribosomal RNA, and homochiral transfer RNA. No one has ever found a plausible abiotic explanation for how life could have become exclusively homochiral. 50

Emily Singer asks: At a chemical level, a deep bias permeates all of biology. The molecules that make up DNA and other nucleic acids such as RNA have an inherent “handedness.” These molecules can exist in two mirror-image forms, but only the right-handed version is found in living organisms. Handedness serves an essential function in living beings; many of the chemical reactions that drive our cells only work with molecules of the correct handedness. DNA takes on this form for a variety of reasons, all of which have to do with intermolecular forces. 42

RNA & DNA: It's prebiotic synthesis: Impossible !!  Homoch11

Phosphorus
Phosphorus is the third essential element making part of the structures of DNA and RNA. It is perfect to form a stable backbone for the DNA molecule. Phosphates can form two phosphodiester bonds with two sugars at the same time and connect two nucleotides. Phosphorus is difficult to dissolve, and that would be a problem both in an aquatic as-as well on a terrestrial environment. Phosphoesters form the backbone of DNA molecules. 

Libretexts explains: A phosphodiester bond occurs when exactly two of the hydroxyl groups in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. Phosphodiester bonds are central to all life on Earth as they make up the backbone of the strands of nucleic acid. In DNA and RNA, the phosphodiester bond is the linkage between the 3' carbon atom of one sugar molecule and the 5' carbon atom of another, deoxyribose in DNA and ribose in RNA. Strong covalent bonds form between the phosphate group and two ribose 5-carbon rings over two ester bonds.  On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.  

That adds up to the fact that concentrations on earth are very low. Kitadai (2017): So far, no geochemical process that led to abiotic production of polyphosphates in high yield on the Earth has been discovered. 39 The phosphate is connected to ribose which is connected to the nitrogenous base. Each of the 3 parts of nucleotides must be just right in size, form, and must fit together. The bonds must have the right forces in order to form the spiral form DNA molecule. And there would have to be enough units concentrated at the same place on the prebiotic earth of the four bases in order to be able to form a self-replicating RNA molecule if the RNA world is supposed to be true. The Albert team explains: A nucleotide is differentiated from a nucleoside by one phosphate group. Accordingly, a nucleotide can also be a nucleoside monophosphate. If more phosphates bond to the nucleotide (nucleoside monophosphate) it can become a nucleoside diphosphate (if two phosphates bond), or a nucleoside triphosphate (if three phosphates bond), such as adenosine triphosphate (ATP). 40 Adenosine triphosphate, or ATP, is the energy currency in the cell, a crucial component of respiration and photosynthesis, amongst other processes. The base, sugar, and phosphate need to be joined together correctly - involving two endothermic condensation reactions involved in joining the nucleotides, which means it has to absorb energy from its surroundings. In other words, compared with polymerization to make proteins, nucleotides are even harder to synthesize and easier to destroy; in fact, to date, there are no reports of nucleotides arising from inorganic compounds in primeval soup experiments.

Bonding the three parts, to form RNA
Supposing that the parts were available, they would have had to be joined together at the same assembly site,  and sorted out from non-functional molecules.  Joining all three components together involves two difficult reactions: formation of a glycosidic bond, with the right stereochemistry linking the nucleobase and ribose, and phosphorylation of the resulting nucleoside.

As Fazale Rana wrote: In order for a molecule to be a self-replicator, it has to be a homopolymer, of which the backbone must have the same repetitive units; they must be identical. In the prebiotic world, for what reason would the generation of a homopolymer be useful? 37

Consider that only random non-designed events could account for the generation, which seems rationally extremely unlikely, if not impossible. The chance for that alone occurring by coincidence is extremely remote. Whatever the mode of joining base and sugar was, it had to be between the correct nitrogen atom of the base and the correct carbon atom of the sugar. The prebiotic synthesis of simple RNA molecules would, therefore, require an inventory of ribose and nucleobases. Assembly of these components into proto-RNA would further require a mechanism to link the ribose and nucleobase together in the proper configuration to form polymers, and then to activate the combined molecule (called a nucleoside) with a pyrophosphate or some other functional component that would promote the formation of a bond between the nucleoside and the growing polymer. 

Terence N. Mitchell explains:  Nucleosides are formed by linking an organic base ( guanine, adenine, uracil or cytosine) to a sugar (here D-ribose). This reaction looks simple, but how it could have occurred by an enzyme-free prebiotic synthesis, in particular involving pyrimidine bases, is an open question. 41

There have been many imaginative ideas and attempts for its solution, all unsuccessful.   In most cases the nucleoside components generated in the experiments, attempting to join the bases to the ribose backbone represent only a minor fraction of a full suite of compounds produced, so the synthesis of a nucleoside would require either that the components be further purified or that some mechanism exist to selectively bring the components together out of a complex mixture. How would non-designed random events be able to attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place?  

Brian J. Cafferty: The coupling of ribose with a base is the first step to form RNA, and even those engrossed in prebiotic research have difficulty envisioning that process, especially for purines and pyrimidines. 40

Phosphodiester bonds
Activated monomers are essential because polymerization reactions occur in an aqueous medium and are therefore energetically uphill in the absence of activation. A plausible energy source for polymerization remains an open question. Condensation reactions driven by cycles of anhydrous conditions and hydration would seem to be one obvious possibility but seem limited by the lack of specificity of the chemical bonds that are formed. 51

Libretexts: Phosphodiester bonds are central to most life on Earth, as they make up the backbone of the strands of DNA. In DNA and RNA, the phosphodiester bond is the linkage between the 3' carbon atom of one sugar molecule and the 5' carbon atom of another, deoxyribose in DNA and ribose in RNA. Strong covalent bonds form between the phosphate group and two 5-carbon ring carbohydrates (pentoses) over two ester bonds. In order for the phosphodiester bond to be formed and the nucleotides to be joined, the tri-phosphate or di-phosphate forms of the nucleotide building blocks are broken apart to give off energy required to drive the enzyme-catalyzed reaction. When a single phosphate or two phosphates known as pyrophosphates break away and catalyze the reaction, the phosphodiester bond is formed. Hydrolysis of phosphodiester bonds can be catalyzed by the action of phosphodiesterases which play an important role in repairing DNA sequences. 52

Prebiotic phosphodiester bond formation
An often-cited claim is that RNA polymerization could be performed on clay. Robert Shapiro wrote a critique in regards to prebiotic proposals of clay-catalyzed oligonucleotide synthesis (2006): 
An extensive series of studies on the polymerization of activated RNA monomers has been carried out by Ferris and his collaborators. A recent publication from this group concluded with the statement: “The facile synthesis of relatively large amounts of RNA oligomers provides a convenient route to the proposed RNA world. The 35–40 oligomers formed are both sufficiently long to exhibit fidelity in replication as well as catalytic activity”. The first review cited above had stated this more succinctly: “The generation of RNAs with chain lengths greater than 40 oligomers would have been long enough to initiate the first life on Earth”. Do natural clays catalyze this reaction? The attractiveness of this oligonucleotide synthesis rests in part on the ready availability of the catalyst. Montmorillonite is a layered clay mineral-rich in silicate and aluminum oxide bonds. It is widely distributed in deposits on the contemporary Earth. If the polymerization of RNA subunits was a common property of this native mineral, the case for RNA at the start of life would be greatly enhanced. However, the “[c]atalytic activity of native montmorillonites before being converted to their homoionic forms is very poor”. The native clays interfere with phosphorylation reactions. This handicap was overcome in the synthetic experiments by titrating the clays to a monoionic form, generally sodium, before they were used. Even after this step, the activity of the montmorillonite depended strongly on its physical source, with samples from Wyoming yielding the best results. Eventually the experimenters settled on Volclay, a commercially processed Wyoming montmorillonite provided by the American Colloid Company 11

Selecting the binding locations
Once the three components would have been synthesized prebiotically, they would have had to be separated from the confusing jumble of similar molecules nearby, and they would have had to become sufficiently concentrated in order to move to the next steps, to join them to form nucleosides, and nucleotides. 

The phosphate/ribose backbone of DNA is hydrophilic (water-loving), so it orients itself outward toward the solvent, while the relatively hydrophobic bases bury themselves inside. 

Xaktly explains: Additionally, the geometry of the deoxyribose-phosphate linkage allows for just the right pitch, or distance between strands in the helix, a pitch that nicely accommodates base pairing. 46
Lots of things come together to create the beautiful right-handed double-helix structure. Production of a mixture of d- and l-sugars produces nucelotides that do not fit together properly, producing a very open, weak structure that cannot survive to replicate, catalyze, or synthesize other biological molecules. 46

Eduard Schreiner (2011): In DNA the atoms C1', C3', and C4' of the sugar moiety are chiral, while in RNA the presence of an additional OH group renders also C2' of the ribose chiral.47

A biological system exclusively uses d-ribose, whereas abiotic experiments synthesize both right- and lefthanded-ribose in equal amounts. But the pre-biological building blocks of life didn’t exhibit such an overwhelming bias. Some were left-handed and some right. So how did right-handed RNA emerge from a mix of molecules?  Some kind of symmetry-breaking process leading to enantioenriched bio monomers would have had to exist. But none is known. Gerald Joyce wrote a science paper that was published in Nature magazine, in 1984. His findings suggested that in order for life to emerge, something first had to crack the symmetry between left-handed and right-handed molecules, an event biochemists call “breaking the mirror.” Since then, scientists have largely focused their search for the origin of life’s handedness in the prebiotic worlds of physics and chemistry, not biology - but with no success. So what is the cop-out? Pure chance !! Luck did the job. That is the only thinkable explanation once God's guiding hand is excluded. How could that be a satisfying answer in face of the immense odds? It is conceivable that the molecules were short enough for all possible sequences, or almost, to be realized (by way of their genes) and submitted to natural selection. This is the way de Duve thought that Intelligent Design could be dismissed. This coming from a Nobel prize winner in medicine makes one wondering, to say the least.  De Duve dismissed intelligent design and replaced it with natural selection. Without providing a shred of evidence. But based on pure guesswork and speculation.

Prebiotic base-pairing
In order to create a stable genome which was necessary for life to start, bases need to be paired between pyrimidines and purines. In molecular biology, complementarity describes a relationship between two structures each following the lock-and-key principle. Complementarity is the base principle of DNA replication and transcription as it is a property shared between two DNA or RNA sequences, such that when they are aligned antiparallel to each other, the nucleotide bases at each position in the sequences will be complementary, much like looking in the mirror and seeing the reverse of things. This complimentary base pairing is essential for cells to copy information from one generation to another. There is no reason why these structures could or would have emerged in this functional complex configuration by random trial and error. A paper from Nature magazine, in 2016, demonstrates the complete lack of explanations despite decades of attempts to solve the riddle. Brian J. Cafferty and colleagues write:

The RNA World hypothesis presupposes that abiotic reactions originally produced nucleotides, the monomers of RNA and universal constituents of metabolism. However, compatible prebiotic reactions for the synthesis of complementary (that is, base pairing) nucleotides and mechanisms for their mutual selection within a complex chemical environment have not been reported. Despite decades of effort, the chemical origin of nucleosides and nucleotides (that is, nucleobases glycosylated with ribose and phosphorylated ribose) remains an unsolved problem.   They then proceed: Here we show that two plausible prebiotic heterocycles, melamine, and barbituric acid, form glycosidic linkages with ribose and ribose-5-phosphate in water to produce nucleosides and nucleotides in good yields. The data presented here demonstrate the efficient single-step syntheses of complementary nucleosides and nucleotides, starting with the plausible proto-nucleobases melamine and BA and ribose or R5P. 9

The problem with such experiments is that they start with Ribose 5-phosphate (R5P) which is already a complex molecule that was not available on the prebiotic earth.  Once all the parts would have been available, they would have had to be joined together at the same assembly site,  and sorted out from non-functional molecules. 

Prebiotic RNA and DNA polymerization
The emergence and existence of catalytic polymers are fundamental. Postulates of how polymerization could have occurred on prebiotic earth are, therefore, another essential question that has not been elucidated. There are no known ways of bringing about this thermodynamically uphill reaction in an aqueous solution: purine nucleosides have been made by dry-phase synthesis, but not even this method has been successful for condensing pyrimidine bases and ribose to give nucleosides. 

Saidul Islam et al pointed out that: Laboratory-based chemical syntheses of ribonucleotides do most, if not all, require manipulation of sugars and nucleobases with protecting group strategies to overcome the thermodynamic and kinetic pitfalls that prevent their fusion. 36

In a research paper from 2010, John D. Sutherland reported: Under plausible prebiotic conditions, condensation of nucleobases with ribose to give β-ribonucleosides is fraught with difficulties. The reaction with purine nucleobases is low-yielding and the reaction with the canonical pyrimidine nucleobases does not work at all.  Fitting the new synthesis to a plausible geochemical scenario is a remaining challenge. 10

Another major problem that origin of life research faces is how to explain the transition from monomer ribonucleotides to polynucleotides.  Libretext: Phosphodiester bonds are central to all life on Earth as they make up the backbone of the strands of nucleic acid. In DNA and RNA, the phosphodiester bond is the linkage between the 3' prime carbon atom of one sugar molecule and the 5' prime carbon atom of another, deoxyribose in DNA and ribose in RNA. In modern cells, in order for the phosphodiester bond to be formed and the nucleotides to be joined, the tri-phosphate or di-phosphate forms of the nucleotide building blocks are broken apart to give off energy required to drive the enzyme-catalyzed reaction. Once a single phosphate or two phosphates (pyrophosphates) break apart and participate in a catalytic reaction, the phosphodiester bond is formed. 38 

Deamer (2010):The general problem regarding the condensation of small organic molecules to form macromolecules in an aqueous environment is the thermodynamically unfavorable process of water removal.In the current biosphere, these types of reactions are catalyzed by enzymes and energetically driven by pyrophosphate hydrolysis. 44

Weber, Arthur L.(1998): Obviously, biocatalysts and energy-rich inorganic phosphorus species were not extant on the Earth before life began. In all cases, the starting problem in a prebiotic synthesis would be the fact that materials would consist of an enormous amount of disparate molecules lying around unordered, and would have had to be separated and sorted out.45

Allaboutscience: The intrinsic nature of the phosphodiester bonds is also finely-tuned. For instance, the phosphodiester linkage that bridges the ribose sugar of RNA could involve the 5’ OH of one ribose molecule with either the 2’ OH or 3’ OH of the adjacent ribose molecule. RNA exclusively makes use of 5’ to 3’ bonding. There are no explanations of how the right position could have been selected abiotically in a repeated manner in order to produce functional polynucleotide chains.  As it turns out, the 5’ to 3’ linkages impart far greater stability to the RNA molecule than do the 5’ to 2’ bonds. Nucleotides can polymerize via condensation reactions.  The activated nucleotides (or the nucleotides with coupling agent) now had to be polymerized. 43


1. R. Shapiro: Life: What]https://jsomers.net/life.pdf]What A Concept! 2008 , page 84
2. Paul G. Higgs: The RNA World: molecular cooperation at the origins of life 11 November 2014
3. 
4. STANLEY L. MILLER: Rates of decomposition of ribose and other sugars: Implications for chemical evolution August 1995 
5. Irina V. Delidovich: Catalytic Formation of Monosaccharides: From the Formose Reaction towards Selective Synthesis 2014
6. Annabelle Biscans: Exploring the Emergence of RNA Nucleosides and Nucleotides on the Early Earth 2018 Dec; 8
7. Cornelia Meinert: Ribose and related sugars from ultraviolet irradiation of interstellar ice analogs 2016 Apr 8
8. ALBERT ESCHENMOSER: [url=https://www.science.org/doi/10.1126/science.284.5423.2118#:~:text=Chemical etiology (2) of nucleic,the molecular basis of life's]Chemical Etiology of Nucleic Acid Structure[/url] 25 Jun 1999
9. Brian J. Cafferty: Spontaneous formation and base pairing of plausible prebiotic nucleotides in water 25 April 2016
10. John D Sutherland: Ribonucleotides 2010 Mar 10.
11. Robert Shapiro: Small Molecule Interactions Were Central to the Origin of Life Review 2006  
12. Robert Shapiro: [url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20907/#:~:text=At 100%C2%B0C the,and T is 56 yr.]Prebiotic cytosine synthesis: A critical analysis and implications for the origin of life[/url] April 13, 1999
13. SAbby Vogel Robinson: Study: Adding UV light helps form ?Missing G? of RNA building blocks June 14, 2010
14. R Shapiro The prebiotic role of adenine: a critical analysis 1995 Jun;25
15. Rani Gupta: [url=https://link.springer.com/chapter/10.1007/978-981-16-0723-3_19#:~:text=other pyrimidine nucleotides.-,Nucleotide biosynthesis is regulated by feedback inhibition%2C feed%2Dforward activation,pathway can inhibit nucleotide biosynthesis.]Nucleotide Biosynthesis and Regulation[/url] 21 April 2021
16. Srivatsan Raman: Evolution-guided optimization of biosynthetic pathways December 1, 2014
17. Daniel Charlier: Regulation of carbamoylphosphate synthesis in Escherichia coli: an amazing metabolite at the crossroad of arginine and pyrimidine biosynthesis 20 September 2018
18. J.Oró: Synthesis of adenine from ammonium cyanide  June 1960
19. James P. Ferris and L. E. Orgel: Studies in Prebiotic Synthesis. I. Aminomalononitrile and 4-Amino-5-cyanoimidazole”” 1966 Aug 20
20. Annabelle Biscans: Exploring the Emergence of RNA Nucleosides and Nucleotides on the Early Earth 6 November 2018
21. Christian de Duve: Singularities: Landmarks on the Pathways of Life 2005
22. Guanine
23. Yasuhiro Oba: Identifying the wide diversity of extraterrestrial purine and pyrimidine nucleobases in carbonaceous meteorites 26 April 2022
24. Anil Oza: Could the Blueprint for Life Have Been Generated in Asteroids? Apr 26, 2022
25. Ben K. D. Pearce: Origin of the RNA world: The fate of nucleobases in warm little ponds October 2, 2017
26. R. Krishnamurthy: Experimentally investigating the origin of DNA/RNA on early Earth 12 December 2018
27. J.D. Sutherland, and Jack W. Szostak: Chemoselective Multicomponent One-Pot Assembly of Purine Precursors in Water November 2, 2010
28. James Urquhart Insight into RNA origins May 13, 2009
29. Caitlin McDermott-Murphy: First building blocks of life on Earth may have been messier than previously thought January 22, 2020
30. Jack W. Szostak* A Model for the Emergence of RNA from a Prebiotically Plausible Mixture of Ribonucleotides, Arabinonucleotides, and 2′-Deoxynucleotides January 8, 2020
31. Florian M. Kruse: Prebiotic Nucleoside Synthesis: The Selectivity of Simplicity 19 May 2020
32. Hidenori Okamura: A one-pot, water compatible synthesis of pyrimidine nucleobases under plausible prebiotic conditions 07 Jan 2019
33. SIDNEY W. FOX Synthesis of Uracil under Conditions of a Thermal Model of Prebiological Chemistry 16 Jun 1961
34. Leslie E Orgel: Prebiotic chemistry and the origin of the RNA world Mar-Apr 2004
35. Cornelia Meinert: Ribose and related sugars from ultraviolet irradiation of interstellar ice analogs 2016 Apr 8
36. Saidu lIslam: Prebiotic Systems Chemistry: Complexity Overcoming Clutter  13 April 2017
37. Fazale Rana: Creating Life in the Lab: How New Discoveries in Synthetic Biology Make a Case for the Creator February 1, 2011
38. [url=https://chem.libretexts.org/Courses/Sacramento_City_College/SCC%3A_Chem_309_-_General_Organic_and_Biochemistry_(Bennett)/Text/13%3A_Functional_Group_Reactions/13.10%3A_Phosphoester_Formation#:~:text=an ester bonds.-,Phosphodiesters,the strands of nucleic acid.]Phosphoester Formation[/url]
39. Norio Kitadai: Origins of building blocks of life: A review July 2018
40. Brian J. Cafferty: Was a Pyrimidine-Pyrimidine Base Pair the Ancestor of Watson-Crick Base Pairs? Insights from a Systematic Approach to the Origin of RNA 23 April 2015
41. Terence N. Mitchell: The “RNA World” 2008
42. Emily Singer New Twist Found in the Story of Life’s Start OCTOBER 11, 2016
43. All about science
44. David Deamer: Bioenergetics and Life's Origins  January 13, 2010
45. Weber, Arthur L.: Prebiotic Polymer Synthesis and the Origin of Glycolytic Metabolism 1998-01-01
46. Xaktly: DNA & RNA: The foundation of life on Earth
47. Eduard Schreiner: Stereochemical errors and their implications for molecular dynamics simulations 2011
48. Steven A. Benner: Asphalt, Water, and the Prebiotic Synthesis of Ribose, Ribonucleosides, and RNA March 28, 2012
49. Rich Deem: Origin of life: latest theories/problems June 2001
50. Change Laura Tan, Rob Stadler: The Stairway To Life: An Origin-Of-Life Reality Check March 13, 2020
51. David Deamer: Bioenergetics and Life's Origins 2010 Feb; 2
52. Libretext: Phosphoester Formation

https://reasonandscience.catsboard.com

Otangelo


Admin

Initially, this could not have happened with a pre-existing polynucleotide template. In the case of RNA, not only must phosphodiester links be repeatedly forged, but they must ultimately connect the 5 prime‑oxygen of one nucleotide to the 3 prime‑oxygen, and not the 2 prime‑oxygen, of the next nucleotide. How could and would random events attach a phosphate group to the right position of a ribose molecule to provide the necessary chemical activity?

The following science paper admits: A fundamental requirement of the RNA world hypothesis is a plausible nonenzymatic polymerization of ribonucleotides that could occur in the prebiotic environment, but the nature of this process is still an open issue. 6

In present-day cells, polymerization is carried out by enzymes with high efficiency and specificity. Enzymes are genetically encoded polymers requiring complex, protein-based synthetic machinery.
Observe what they write at the conclusion:

Selection toward highly efficient catalytic peptides, which eventually resulted in present-day enzymes, could have started at a very early stage of chemical evolution.

This is an entirely unsupported claim. Readers without training in biochemistry will simply believe it, without further questioning. And that is what goes in basically the entire scientific literature that deals with origins. Nothing besides just-so stories based on evolutionary guesswork !! In living organisms today, adenosine-5'-triphosphate (ATP) is used for the activation of nucleoside phosphate groups, but ATP would not be available for prebiotic syntheses. Joyce and Orgel note the possible use of minerals for polymerization reactions, but then express their doubts about this possibility.

Robert P. Bywater informed: Despite the wide repertoire of chemical and biological properties of RNA, which make it such an appealing contender for being the first type of molecular species to usher in life onto this planet, there is no explanation for how such a complex chemical species could have arisen in the absence of sophisticated chemical machinery. The generation of complex chemicals requires many millions of cycles of synthesis, partial degradation, concentration, selection, and reannealing in combinatorially new ways such that sufficiently diverse species could be produced and reproduced, from which particularly suitable entities survived 3

General hurdles
Prebiotic synthesis entails a number of different difficulties.

1.Natural selection
There was no selection on early earth. In the living world, complex molecular machines are pre-programmed to make the building blocks of life, precisely as needed. The nucleic acids for a limited set, so do the 20 amino acids, and they come in the functional enantiomeric form, and those that are wrong, like right-handed amino acids, are sorted out by the cell machinery. None of this was available prebiotically. There was a jumble and a chaotic mess of all sorts of molecules without any order.

2. Time
Time is not the naturalist's friend. There are chemical reactions performed by certain classes of enzymes, that speed up the process billions of times.  Without the OMP decarboxylase enzyme, a reaction ‘“absolutely essential” in creating the building blocks of DNA and RNA would take 78 million years in the water. Some chemical reactions are so unspecific that getting the right one by unguided means resorting to time and enough attempts of trial and error can very easily lead to huge numbers of odds that exceed the number of atoms in the entire universe ( 10^80).

3. Getting pure materials.
Evidently, what chemists do in the lab, namely using pure reagents, was not what happened on the early earth. Impure contamination in the pool of chemicals was the state of affairs. In order to recreate what was going on back then, chemists would have to recreate as close as possible the situation on the early earth, which includes using contaminated chemicals. 

4.Activation and repetitive processes
Monomers need to be activated in order for polymerization and catenation to make amino acid strands, and genes, to be possible. That demands a repetitive ordered process, where the bond reactions happen repeatedly at the same place in the molecules. In RNA or DNA polymerase protein complexes, or in the ribosome, sophisticated molecular machines perform these reactions with exuberant precision and efficiency. Science has failed to explain how that could have happened on the early earth.

5.Protected environments
If these chemical reactions had happened in places being exposed to UV radiation, no deal. If it was too cold, or too hot, too acidic, or too alkaline, in the wrong atmospheric conditions, no deal.

Shapiro (2006): Prebiotic syntheses conducted in the laboratory often involve multistep procedures, with purified reagents and very different conditions permitted at each new step. The extensive purification procedures and changes of locale that would be needed to produce comparable results on the early Earth are seldom discussed but must be taken into account when attempting to judge the plausibility of the entire sequence. 1

6. The right sequence of reactions
In metabolic pathways in the cell, the enzymes, our sophisticated molecular robots, are lined up in the right sequence. Once a manufacturing step by enzyme one is concluded, and the intermediate product is ready, it is handed over to enzyme two, which uses the product of the previous enzyme, to perform the subsequent manufacturing step. If the enzyme sequence were wrong, no deal, and the entire manufacturing process in the production line breaks down. On prebiotic earth, natural catalysts, like ions, clay, etc. had to replace enzymatic reactions. How could the right sequence have been performed? its far from realistic to believe that order, timing, and the right subsequent reactions could have been performed by random chaotic events without direction.  

ROBERT SHAPIRO clarifies some important points. He was interviewed by J.Craig Venter in 2008:

 I then spent decades running a laboratory in DNA chemistry, and so many people were working on DNA synthesis — which has been put to good use as you can see — that I decided to do the opposite, and studied the chemistry of how DNA could be kicked to Hell by environmental agents. Among the most lethal environmental agents I discovered for DNA — pardon me, I'm about to imbibe it — was water. Because water does nasty things to DNA. For example, there's a process called DNA animation, where it kicks off part of the coding part of DNA from the units — that was discovered in my laboratory. Another thing water does is help the information units fall off of DNA, which is called depurination and ought to apply only one of the subunits — but works under physiological conditions for the pyrimidines as well, and I helped elaborate the mechanism by which water helped destroy that part of DNA structure. 

Since then, so-called prebiotic chemistry, which is of course falsely named, because we have no reason to believe that what they're doing would ever lead to life — I just call it 'investigator influenced abiotic organic chemistry' — has fallen into the same trap. In the proceedings of the National Academy of Sciences about two months ago there was a paper — I think it was theoretical — they showed that in certain hydro-thermal events, convection forces and other attractive forces, about which I am unable to comment, would serve to concentrate organic molecules so that organic molecules would get much more concentrated in the bottom of this than they would in the ordinary ocean. Very nice, perhaps it's a good place for the origin of life, and interesting finding, but then there was another commentary paper in the Proceedings by another invited commentator, who said,
Great advance for RNA world because if you put nucleotides in, they'll be concentrated enough to form RNA; and if you put RNA in, the RNA will come together and form aggregates, giving you much more chance of forming a ribosome or whatever. I looked at the paper and thought, How did nucleotides come in? How did RNA come in? How did anything come in? The point is, you would take whatever mess prebiotic chemistry gives you and you would concentrate that mess so it's relevant to RNA or the origin of life — it's all in the eye of the beholder. And almost all of prebiotic chemistry is like this; they take chemicals of their own selection.

People were talking about Steve Benner and his borate paper where he selected, of his own free will, the chemical formaldehyde, the chemical acid-aldehyde, and the mineral borate, and he decided to mix them together and got a product that he himself said was significant in leading to the origin of RNA world, and I, looking at the same thing, see only the hands of Steve Benner reaching to the shelf of organic chemicals, picking formaldehyde, and from another shelf, picking acidaldehyde, etc. Excluding them carefully. Picking a mineral that occurs only in selective places on the Earth and putting it in heavy doses. And at the end getting a complex of ribose and borate, which by itself would be of no use for making RNA, because the borate loves to hold onto the ribose, and as long as it holds onto the ribose it can't be used to make RNA. If it lets go of the ribose, then the ribose becomes vulnerable to destruction by all the other environmental agents. The half-life of pure ribose in solution, a different experiment and a very good one, by Stanley Miller is of the order of one or two hours, and all of the other sugars prominent in Earth biology have similar instability.

I was publishing papers like this and I got the reputation, or the nickname in the laboratory of the prebiotic chemist, of 'Dr. No'. If someone wanted a paper murdered, send it to me as a referee. At some point, someone said, Shapiro, you've got to be positive somewhere. So how did life start? And do we have any examples of authentic abiotic chemistry, not subject to investigator interference? The only true samples we have are those meteorites, which are scooped up quickly and often fallen in an unspoiled place — there was a famous meteorite that fell in France in a sheep field in the 1840s and led to dreadful chemistry of people seeing all sorts of biomolecules in it, not surprisingly. But if you took pristine meteorites and look inside, what you see are a predominance of simple organic compounds. The smaller the organic compound, the more likely it is to be present. The larger it is, the less likely it is to be present. Amino acids, yes, but the simplest ones. Over a hundred of them. All the simplest ones, some of which, coincidentally, overlap the unique set of 20 that coincide with Earth life, but not containing the larger amino acids that overlap with Earth life. 

And no sample of a nucleotide, the building block of RNA or DNA, has ever been discovered in a natural source apart from Earth life. Or even take off the phosphate, one of the three parts, and no nucleoside has ever been put together. Nature has no inclination whatsoever to build nucleosides or nucleotides that we can detect, and the pharmaceutical industry has discovered this. Life had to start with the mess — a miscellaneous mixture of organic chemistry to begin with. How do you organize this? You have to have a preponderance of some chemicals or lacking others would be against the second law of thermo-dynamics — it violates a concept that as a non-physicist that I barely grasp called 'entropy'.

In the simplest case, and there may be many more elaborate cases, they found that the energy wouldn't be released unless some chemical transformations took place. If the chemical transformations took place then the energy was released, a lot of it is heat. If this just went on continuously, all you do is use up the energy. Release all of it and you've converted one chemical to another. Big deal. To get things interesting, you have to close the cycle where the chemicals can be recycled by processes of their own, and then go through it again, releasing more energy. And once you have that, you can then develop nodes — because organic chemistry is very robust, there are reaction pathways leading everywhere, which is why it's such a mess.

One doesn't need a freak set of perhaps a hundred consecutive reactions that will be needed to make an RNA, and life becomes a probable thing that can be generated through the action of the laws of chemistry and physics, provided certain conditions are met. You must have the energy. It's good to have some container or compartment because if your products just diffuse away from each other and get lost and cease to react with one another you'll eventually extinguish the cycle. You need a compartment, you need a source of energy, you need to couple the energy to the chemistry involved, and you need sufficiently rich chemistry to allow for this network of pathways to establish itself. Having been given this, you can then start to get evolution.

RNA & DNA: It's prebiotic synthesis: Impossible !!  Robert11

Shapiro wrote in: A Skeptic's Guide to the Creation of Life on Earth 1986, p.186:

In other words,' I said, `if you want to create life, on top of the challenge of somehow generating the cellular  components out of non-living chemicals, you would have an even bigger problem in trying to it the ingredients together in the right way.' `Exactly! ... So even if you could accomplish the thousands of steps between the amino acids in the Miller tar-which probably didn't exist in the real world anyway-and the components you need for a living cell-all the enzymes, the DNA, and so forth-you's still immeasurably far from life. ... the problem of  assembling the right parts in the right way at the right time and at the right place, while keeping out the wrong material, is simply insurmountable. 5

A. Graham Cairns-Smith also lists several hurdles that would have to be overcome in his book: Genetic takeover, page 64:

What is missing from this story of the evolution of life on earth is the original means of producing such sophisticated materials as RNA. The main problem is that the replication of RNA depends on a clean supply of rather complicated monomers—activated nucleotides. What was required to set the scene for an RNA world was a highly competent, long-term means of production of at least two nucleotides. In practice the discrimination required to make nucleotide parts cleanly, or to assemble them correctly, still seems insufficient. 

The implausibility of prevital nucleic acid If it is hard to imagine polypeptides or polysaccharides in primordial waters it is harder still to imagine polynucleotides. But so powerful has been the effect of Miller’s experiment on the scientific imagination that to read some of the literature on the origin of life (including many elementary texts) you might think that it had been well demonstrated that nucleotides were probable constituents of a primordial soup and hence that prevital nucleic acid replication was a plausible speculation based on the results of experiments. There have indeed been many interesting and detailed experiments in this area. But the importance of this work lies, to my mind, not in demonstrating how nucleotides could have formed on the primitive Earth, but in precisely the opposite: these experiments allow us to see, in much greater detail than would otherwise have been possible, just why prevital nucleic acids are highly implausible. Let us consider some of the difficulties to make RNA & DNA

1. as we have seen, it is not even clear that the primitive Earth would have generated and maintained organic molecules. All that we can say is that there might have been prevital organic chemistry going on, at least in special locations.
2. high-energy precursors of purines and pyrimidines had to be produced in a sufficiently concentrated form (for example at least 0.01 M HCN).
3. the conditions must now have been right for reactions to give perceptible yields of at least two bases that could pair with each other.
4. these bases must then have been separated from the confusing jumble of similar molecules that would also have been made, and the solutions must have been sufficiently concentrated.
5. in some other locations a formaldehyde concentration of above 0.01 M must have built up.
6. this accumulated formaldehyde had to oligomerize to sugars.
7. somehow the sugars must have been separated and resolved, so as to give a moderately good concentration of, for example, D-ribose.
8. bases and sugars must now have come together.
9. they must have been induced to react to make nucleosides. (There are no known ways of bringing about this thermo dynamically uphill reaction in an aqueous solution: purine nucleosides have been made by dry phase synthesis, but not even this method has been successful for condensing pyrimidine bases and ribose to give nucleosides
10. Whatever the mode of joining base and sugar it had to be between the correct nitrogen atom of the base and the correct carbon atom of the sugar. This junction will fix the pentose sugar as either the a- or fl-anomer of either the furanose or pyranose forms. For nucleic acids, it has to be the fl-furanose. (In the dry-phase purine nucleoside syntheses referred to above, all four of these isomers were present with never more than 8 ‘Z, of the correct structure.)
11. phosphate must have been, or must now come to have been, present at reasonable concentrations. (The concentrations in the oceans would have been very low, so we must think about special situations—evaporating lagoons etc.   
12. the phosphate must be activated in some way — for example as a linear or cyclic polyphosphate — so that (energetically uphill) phosphorylation of the nucleoside is possible.
13. to make standard nucleotides only the 5’- hydroxyl of the ribose should be phosphorylated. (In solid-state reactions with urea and inorganic phosphates as a phosphorylating agent, this was the dominant species to begin with. Longer heating gave the nucleoside cyclic 2’,3’-phosphate as the major product although various dinucleotide derivatives and nucleoside polyphosphates are also formed
14. if not already activated — for example as the cyclic 2’,3’-phosphate — the nucleotides must now be activated (for example with polyphosphate) and a reasonably pure solution of these species created of reasonable concentration. Alternatively, a suitable coupling agent must now have been fed into the system.
15. the activated nucleotides (or the nucleotides with coupling agent) must now have polymerized. Initially this must have happened without a pre-existing polynucleotide template (this has proved very difficult to simulate ; but more important, it must have come to take place on pre-existing polynucleotides if the key function of transmitting information to daughter molecules was to be achieved by abiotic means. This has proved difficult too. Orgel & Lohrmann give three main classes of problem.
(i) While it has been shown that adenosine derivatives form stable helical structures with poly(U) — they are in fact triple helixes — and while this enhances the condensation of adenylic acid with either adenosine or another adenylic acid — mainly to di(A) - stable helical structures were not formed when either poly(A) or poly(G) Were used as templates.
(ii) It was difficult to find a suitable means of making the internucleotide bonds. Specially designed water-soluble carbodiimides were used in the experiments described above, but the obvious pre-activated nucleotides — ATP or cyclic 2’,3’-phosphates — were unsatisfactory. Nucleoside 5'-phosphorimidazolides, for example N/\ n K/N/P-r’o%OHN/\N were more successful, but these now involve further steps and a supply of imidazole, for their synthesis.
(iii) Internucleotide bonds formed on a template are usually a mixture of 2’—5’ and the normal 3’—5’ types. Often the 2’—5’ bonds predominate although it has been found that Zn“, as well as acting as an eflicient catalyst for the template-directed oligomerization of guanosine 5’-phosphorimidazolide also leads to a preference for the 3’—5’ bonds.
16. the physical and chemical environment must at all times have been suitable — for example the pH, the temperature, the M2+ concentrations.
17. all reactions must have taken place well out of the ultraviolet sunlight; that is, not only away from its direct, highly destructive effects on nucleic acid-like molecules, but away too from the radicals produced by the sunlight, and from the various longer lived reactive species produced by these radicals.
18. unlike polypeptides, where you can easily imagine functions for imprecisely made products (for capsules, ionexchange materials, etc), a genetic material must work rather well to be any use at all — otherwise it will quickly let slip any information that it has managed to accumulate.
19. what is required here is not some wild one-off freak of an event: it is not true to say ‘it only had to happen once’. A whole set-up had to be maintained for perhaps millions of years: a reliable means of production of activated nucleotides at the least.


RNA & DNA: It's prebiotic synthesis: Impossible !!  Cairns10

As the difficulties accumulate the stakes get higher: success would be all the more resounding, but it becomes less likely. Sooner or later it becomes wiser to put your money elsewhere.
 2

M. Gargaud and colleagues detail the size of the problem:

One of the principal problems concerning the hypothesis of the RNA world is that it appears quite unlikely that a prebiotic environment could have existed containing the mixture of activated nucleotides favoring the formation and replication of ribozymes, as well as their evolution through natural selection. Even if there were several candidate reactions for the efficient prebiotic synthesis of nucleic bases, access to monomeric nucleotides by chemical pathways in fact comes up against several obstacles. If one goes no further than mimicking the biochemical pathway, the first difficulty that occurs is that of synthesizing ribose, which is formed in just negligible quantities within the complex mixture obtained by polymerization of formaldehyde, and, what is more, has a limited lifetime. The bond between a nucleic base and ribose that produces a nucleoside is then a  very difficult reaction. There still remains the matter of obtaining a nucleotide by phosphorylation, which leads to mixtures because three positions remain available on the ribose, and then there is its activation. So there are two possibilities, either to envisage an easier pathway for the prebiotic synthesis of nucleotides or to squarely reject RNA as the initial bearer of information, in favor of an alternative bearer that has not left any evolutionary traces. 4

Unsolved issues regarding nucleic acid synthesis 
How would the early Earth have generated and maintained organic molecules? All that can be said is that there might have been prebiotic organic chemistry going on, at least in special locations.
How would prebiotic processes have purified the starting molecules to make RNA and DNA which were grossly impure? They would have been present in complex mixtures that contained a great variety of reactive molecules.
How did the synthesis of the nitrogenic nucleobases in prebiotic environments occur?
How did fortuitous accidents select the five just-right nucleobases to make DNA and RNA, Two purines, and three pyrimidines?
How did unguided non-designed events select purines with two rings, with nine atoms, forming the two rings: 5 carbon atoms and 4 nitrogen atoms, amongst almost unlimited possible configurations?
How did lucky coincidence pick pyrimidines with one ring, with six atoms, forming its ring: 4 carbon atoms and 2 nitrogen atoms, amongst an unfathomable number of possible configurations?
How did random trial and error foresee that this specific atomic arrangement of the nucleobases is required to get the right strength of the hydrogen bond to join the two DNA strands and form Watson–Crick base-pairing?
How did mechanisms without external direction foresee that this specific atomic arrangement would convey one of, if not the best possible genetic system to store information?
How would these functional bases have been separated from the confusing jumble of similar molecules that would also have been made?
How were high-energy precursors to produce purines and pyrimidines produced in a sufficiently concentrated form and joined to the assembly site?
How could the adenine-uracil interaction function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup" considering that its interaction is weak and nonspecific?
How could the ribose 5 carbon sugar rings which form the RNA and DNA backbone have been selected, if 6 or 4 carbon rings, or even more or less, are equally possible but non-functional?
How would the functional ribose molecules have been separated from the non-functional sugars?
How could right-handed configurations of RNA and DNA have been selected in a racemic pool of right and left-handed molecules? Ribose must have been in its D form to adopt functional structures ( The homochirality problem )
How was exclusively β-D-ribofuranose chosen in nucleic acids over pyranose, given that the former species are substantially more stable at equilibrium?
How were the correct nitrogen atom of the base and the correct carbon atom of the sugar selected to be joined together?
How could random events have brought all the 3 parts together and bonded them in the right position ( probably over one million nucleotides would have been required ?)
How could prebiotic reactions have produced functional nucleosides? (There are no known ways of bringing about this thermodynamically uphill reaction in aqueous solution)
How could prebiotic glycosidic bond formation between nucleosides and the base have occurred if they are thermodynamically unstable in water, and overall intrinsically unstable?
How could  RNA nucleotides have accumulated, if they degrade at warm temperatures in time periods ranging from nineteen days to twelve years? These are extremely short survival rates for the four RNA nucleotide building blocks.
How was phosphate, the third element, concentrated at reasonable concentrations?. (The concentrations in the oceans or lakes would have been very low)
How would prebiotic mechanisms phosphorylate the nucleosides at the correct site (the 5' position) if, in laboratory experiments, the 2' and 3' positions were also phosphorylated?
How could phosphate have been activated somehow? In order to promote the energy dispendious nucleotide polymerization reaction, and (energetically uphill) phosphorylation of the nucleoside had to be possible.
How was the energy supply accomplished to make RNA? In modern cells, energy is consumed to make RNA.
How could a transition from prebiotic to biochemical synthesis have occurred? There are a huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network.
How could  RNA have formed, if it requires water to make them, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place?
How would the prebiotic synthesis transition of RNA to the highly regulated cellular metabolic synthesis have occurred?  The pyrimidine synthesis pathway requires six regulated steps, seven enzymes, and energy in the form of ATP.
The starting material for purine biosynthesis is Ribose 5-phosphate, a product of the highly complex pentose phosphate pathway, which uses 12 enzymes. De novo purine synthesis pathway requires ten regulated steps, eleven enzymes, and energy in the form of ATP.
How did formaldehyde concentration of above 0.01 M build up?
How did accumulated formaldehyde oligomerise to sugars?
How were they induced to react to make nucleosides? (There are no known ways of bringing about this thermo dynamically uphill reaction in aqueous solution: purine nucleosides have been made by dry phase synthesis, but not even this method has been successful for condensing pyrimidine bases and ribose to give nucleosides

1. Robert Shapiro: Small Molecule Interactions were Central to the Origin of Life 2006
2. A. Graham Cairns-Smith: Genetic Takeover: And the Mineral Origins of Life 1988
3. Robert P. Bywater writes in: On dating stages in prebiotic chemical evolution 15 February 2012

4. M. Gargaud: Young Sun, Early Earth  and the Origins of Life 2012
5. Robert Shapiro: Origins : A Skeptic's Guide to the Creation of Life on Earth  January 1, 1986
6. Dr. Rafał Wieczorek: Formation of RNA Phosphodiester Bond by Histidine-Containing Dipeptides 18 December 2012

https://reasonandscience.catsboard.com

Sponsored content



Back to top  Message [Page 1 of 1]

Permissions in this forum:
You cannot reply to topics in this forum