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Intelligent Design, the best explanation of Origins » Origin of life » The RNA & DNA World » RNA & DNA: It's prebiotic synthesis: Impossible !!

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

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

http://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!

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.'


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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

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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.

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Crick, Watson and Wilkins shared the 1962 Nobel Prize for Physiology or Medicine, Franklin having died of cancer in 1958.

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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. 

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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. 

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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.

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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
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Nucleotide bases appear in two forms: A single-ring nitrogenous base, called a pyrimidine, and a double-ringed base, called a purine.


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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

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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.

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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.

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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."

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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.

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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

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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.

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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.

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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). 

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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


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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. 

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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.

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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

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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. 

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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 ? 

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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? 

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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? 

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In his following book, Genetics of Original Sin, he then extended a bit further, and exposed what he meant by "heuristically sterile". 

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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 Admin on Sat Jun 15, 2019 6:12 pm; edited 142 times in total

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1b. Selecting the right backbone ribose sugar
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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.

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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
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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.

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

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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.






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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

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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.



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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
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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.

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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. 

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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

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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.

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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.

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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.

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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? 
 

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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 

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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 
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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.


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“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


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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. 

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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.

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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, 


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



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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 
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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. 

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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. 

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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. 

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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.


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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. 

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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?

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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.

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The pathway to make purines is even more complex, as can be seen in the picture above.  The pathway consists of 11 enzymatic steps.

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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. 

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And that brings us again to the catch-22 situation as mentioned before:

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essential basically means, irreducible....

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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. 

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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.

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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.

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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. 

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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. 

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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.

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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.

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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.

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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.



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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.

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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

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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.


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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 Admin on Sat Jun 15, 2019 9:43 am; edited 62 times in total

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Biochemical fine-tuning - essential for life
http://reasonandscience.catsboard.com/t2591-biochemical-fine-tuning-essential-for-life

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

Formation of RNA Phosphodiester Bond by HistidineContaining Dipeptides 
http://sci-hub.tw/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.tw/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.tw/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.tw/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.tw/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.tw/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.tw/https://www.ncbi.nlm.nih.gov/pubmed/25608919

Studies on the origin of life  the end of the beginning
http://sci-hub.tw/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.tw/https://www.ncbi.nlm.nih.gov/pubmed/15217990



Last edited by Admin on Tue Jun 11, 2019 1:28 pm; edited 3 times in total

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

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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!

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.'

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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!

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.'

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