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Defending the Christian Worlview, Creationism, and Intelligent Design

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Defending the Christian Worlview, Creationism, and Intelligent Design » Origin of life » The RNA & DNA World » DNA & origin of life scenarios

DNA & origin of life scenarios

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1DNA & origin of life scenarios Empty DNA & origin of life scenarios Tue Sep 11, 2018 12:24 pm

Otangelo


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DNA & origin of life scenarios

The importance of finding convincing prebiotic pathways to synthesize nucleosides and nucleotides cannot be overestimated. One can almost say that the world is waiting for the answer for more than 60 years.



Nucleoside Diphosphate Kinase

For three of the four nucleotides—ADP, CDP, and GDP—the conversion from diphosphate (dNDP) to the triphosphate (dNTP) involves simply a phosphorylation of the rNDP reductase product, catalyzed by nucleoside diphosphate kinase. In most cells, this enzyme is very active, and all known forms of the enzyme have very low specificity. Thus, the enzyme catalyzes the reversible transfer of the g-phosphate of any common rNTP or dNTP to the phosphate at the b-position of any common rNDP or dNDP. The equilibrium constant for each reaction catalyzed is close to unity. Thus, the direction in which a nucleoside diphosphate kinase-catalyzed reaction occurs in vivo depends on the concentrations of substrates and products. Because ATP is almost always the most abundant intracellular nucleoside triphosphate, most such reactions involve the ATP-dependent conversion of a ribo- or deoxyribonucleoside diphosphate to the corresponding triphosphate.

Adenine

Adenine is one of the most important organic molecules for life as we know it today.

Adenine and guanine are derived from the nucleotide inosine monophosphate (IMP), which in turn is synthesized from a pre-existing ribose phosphate through a complex pathway using atoms from the amino acids glycine, glutamine, and aspartic acid, as well as the coenzyme tetrahydrofolate. 12

Adenine is one of the most important organic molecules for life as we know it today.

Adenine is an integral part of DNA, RNA, and ATP. DNA, as you might know, is the genetic code used for cellular life on earth. It is through the precise inheritance of on organism's DNA from its parent that the traits of an organism are passed on. Here is the partial structure of DNA with an Adenine group attached. Adenine is a purine. Purines are six-membered rings attached to five-membered rings. When Adenine is attached to DNA, it forms a bond with another molecule called Thymine, a pyrimidine, on the other side of the DNA strand. It is these bonds which give DNA its double-helix structure. The sequence of DNA, or the order in which nucleotides are placed, allows for the diversity among all living organisms. The importance of Adenine to RNA is similar to that of DNA.

Besides DNA and RNA, Adenine is also an important part of adenosine triphosphate, or ATP. Adenosine triphosphate is the nitrogenous base adenine bonded to a five-carbon sugar. This molecule is important because it has the ability to phosphorylize, or add a phosphate group to, other molecules. This transfer of a phosphate group allows energy to be released. It is this energy which is used by cells in living organisms. This is why the molecules ATP, and its nitrogenous base Adenine, are so important.

"Adenine synthesis is perhaps the best example of an irreducibly complex system that can be found in life ..."

The process doesn't work unless all 11 enzymes are present. ( So we have a chicken/egg problem here )

Adenine synthesis requires unreasonable HCN concentrations. Adenine deaminates with a half-life of 80 years (at 37°C, pH 7). 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."

In biochemistry, the addition of a formyl functional group is termed formylation. A formyl functional group consists of a carbonyl bonded to hydrogen. When attached to an R group, a formyl group is called an aldehyde. 3

b 10-Formyltetrahydrofolate (10-CHO-THF) is a form of tetrahydrofolate that acts as a donor of formyl groups in anabolism. In these reactions, 10-CHO-THF is used as a substrate in formyltransferase reactions. This is important in purine biosynthesis, where 10-CHO-THF is a substrate for phosphoribosylaminoimidazolecarboxamide formyltransferase, as well as in the formylation of the methionyl initiator tRNA (fMet-tRNA), when 10-CHO-THF is a substrate for methionyl-tRNA formyltransferase 4 

Adenine biosynthesis

The key riddle remains: how do five HCN molecules combine to form adenine under prebiotic conditions? 3

Although the formation of adenine by the pentamerization of HCN is very exothermic, this process is quite unlikely in isolation (gas phase). Not only must five HCN molecules come together, but also the reaction barriers are very high. The intimate participation of an additional molecule, such as H2O or NH3 (or perhaps HCN) is needed to lower the barriers considerably to realistic energies.

Adenine is an integral part of DNA, RNA, and ATP. DNA, as you might know, is the genetic code used for cellular life on earth. It is through the precise inheritance of on organism's DNA from its parent that the traits of an organism are passed on. Here is the partial structure of DNA with an Adenine group attached. Adenine is a purine. Purines are six-membered rings attached to five membered rings. When Adenine is attached to DNA, it forms a bond with another molecule called Thymine, a pyrimidine, on the other side of the DNA strand. It is these bonds which give DNA its double-helix structure. The sequence of DNA, or the order in which nucleotides are placed, allows for the diversity among all living organisms. The importance of Adenine to RNA is similar to that of DNA.

Besides DNA and RNA, Adenine is also an important part of adenosine triphosphate, or ATP. Adenosine triphosphate is the nitrogenous base adenine bonded to a five carbon sugar. This molecule is important because it has the ability to phosphorylize, or add a phosphate group to, other molecules. This transfer of a phosphate group allows energy to be released. It is this energy which is used by cells in living organisms. This is why the molecules ATP, and its nitrogenous base Adenine, are so important.

"Adenine synthesis is perhaps the best example of an irreducibly complex system that can be found in life ..."

the process doesn't work unless all 11 enzymes are present.

Adenine synthesis requires unreasonable HCN concentrations. Adenine deaminates with a half-life of 80 years (at 37°C, pH 7). 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." 1

Shapiro also critically analyzed prebiotic simulation experiments that produced the DNA and RNA component adenine. As with cytosine, he showed that adenine formation on early Earth (by currently recognized prebiotic routes) could not reasonably have occurred, for many of the same reasons. 2

DNA & origin of life scenarios Intell10

DNA & origin of life scenarios Www_id10

Adenine biosynthesis pathway :

DNA & origin of life scenarios Nucleo11

https://books.google.com.br/books?id=5ZGUD49fMcAC&pg=PA206&lpg=PA206&dq=Metabolic+pathways,+irreducible+complexity&source=bl&ots=FdagRE2T-M&sig=pVeMIrlHluDJSkL2Bp3Si4M4Xh4&hl=pt-BR&sa=X&ei=s1pNVZPQAcmpNsb8gbAH&ved=0CFsQ6AEwBzge#v=onepage&q=Metabolic%20pathways%2C%20irreducible%20complexity&f=false

DNA & origin of life scenarios Adenin10

Amidophosphoribosyltransferase

Prebiotic cytosine synthesis: A critical analysis and implications for the origin of life 4

The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses. If cytosine concentrations are to be maintained on a worldwide basis, then synthesis must be sufficient to replace depletion. The syntheses described thus far do not possess the necessary speed and selectivity to meet this requirement. The use of drying lagoons as a site for prebiotic synthesis has been suggested as a remedy: synthetic rates would be enhanced by greatly increasing the concentration of the reagents. The lagoon suggestion appears geologically implausible, however. All schemes in which cytosine is synthesized locally and distributed globally also are handicapped in that the enormous dilution that takes place when cytosine is released into a global sea offsets any gain in synthetic efficiency.

Guanine 

Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA. 

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.

Thymine 

DNA can only be replicated in the presence of  specific enzymes (described below )  which can only be manufactured by the already existing DNA. Each is absolutely essential for the other, and both must be present for the DNA to multiply. Therefore, DNA has to have been in existence in the beginning for life to be controlled by DNA. Scott M. Huse, "The Collapse of Evolution", Baker Book House: Grand Rapids (Michigan), 1983 p:93-94

Thymidylate synthases (Thy) are key enzymes in the synthesis of deoxythymidylate, 1 of the 4 building blocks of DNA. As such, they are essential for all DNA-based forms of life and therefore implicated in the hypothesized transition from RNA genomes to DNA genomes. Two  unrelated Thy enzymes, ThyA and ThyX, are known to catalyze the same biochemical reaction. 7 

Thymidylate synthase (Thy) is a fundamental enzyme in DNA synthesis because it catalyzes the formation of deoxythymidine 5′-monophosphate (dTMP) from deoxyuridine 5′-monophosphate (dUMP). For decades, only one family of thymidylate synthase enzymes was known, and its presence was considered necessary to maintain all DNA-based forms of life. Then, a gene encoding an alternative enzyme was discovered and characterized , and the novel enzyme was named ThyX, whereas the other enzyme was renamed ThyA. Even though both reactions accomplish the same  key step, the reaction mechanisms, or steps, catalyzed by the FDTS and TS enzymes are structurally different. The 2 enzymes, ThyA and ThyX, were found to have distinctly different sequences and structures, thus alluding to independent  origins.

Thats interesting, as we find two distinct enzymes with two different sequences and structures synthesizing the same reaction, thus being a example of convergence right in the beginning. How remote was the chance for this to happen by natural means , considering, that convergence does not favour naturalistic explanations ? 

as  Stephen J.Gould wrote: “…No finale can be specified at the start, none would ever occur a second time in the same way, because any pathway proceeds through thousands of improbable stages. Alter any early event, ever so slightly, and without apparent importance at the time, and evolution cascades into a radically different channel.1

Stephen J. Gould, Wonderful Life: The Burgess Shale and the Nature of History (New York, NY: W.W. Norton & Company, 1989), 51.

By virtue of their function and phyletic distribution, Thys are ancient enzymes, implying 1) the likely participation of one or both enzymes during the transition from an RNA world to a DNA world (based on protein catalysts: Joyce 2002) and 2) the probable presence of a gene encoding Thy in the genome of the common ancestors of eukaryotes, bacteria, and archaea . Thus, tracing back the  pathway of genes encoding ThyA and ThyX may shed light on the actively debated wider issue regarding the origins of viral and cellular DNA 

This brings us to the same problem as with Ribonucleotide Reductase enzymes (RNR), which is the classic chicken and egg, catch22 situation.  ThyA and ThyX enzymes are required to make DNA. DNA is however required to make these enzymes. What came first ??  We can conclude with high certainty that this enzyme buries any RNA world fantasies, and any possibility of transition from  RNA to DNA world scenarios, since both had to come into existence at the same time.
Prebiotic cytosine synthesis

Cytosine  is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA).

Cytosine  has not been reported in analyses of meteorites nor is it among the products of electric spark discharge experiments. The reported prebiotic syntheses of cytosine involve the reaction of cyanoacetylene (or its hydrolysis product, cyanoacetaldehyde), with cyanate, cyanogen, or urea. These substances undergo side reactions with common nucleophiles that appear to proceed more rapidly than cytosine formation. To favor cytosine formation, reactant concentrations are required that are implausible in a natural setting. Furthermore, cytosine is consumed by deamination (the half-life for deamination at 25°C is ≈340 yr) and other reactions. No reactions have been described thus far that would produce cytosine, even in a specialized local setting, at a rate sufficient to compensate for its decomposition. 1

The evidence that is available at the present time does not support the idea that RNA, or an alternative replicator that uses the current set of RNA bases, was present at the start of life.

The RNA/DNA base cytosine is not produced in spark discharge experiments. The proposed prebiotic productions are chemically unrealistic because the alleged precursors are unlikely to be concentrated enough, and they would undergo side reactions with other organic compounds, or hydrolyse.  Cytosine itself is too unstable to accumulate over alleged geological ‘deep time’, as its half life for deamination is 340 years at 25 °C.  2

For a long time the synthesis of RNA monomers under prebiotic conditions appeared to be a fundamental problem since the condensation of sugar (ribose) and nucleobase (purines and pyrimidines) does not work (Orgel, 2004). The prebiotic synthesis of purine ribonucleotides is still unclear, yet recently a breakthrough has been made with regard to the synthesis of pyrimidine ribonucleotide monomers (which incorporate cytosine and uracil). It now appears in principle to be solved, in a completely unexpected manner. The study by the group of John Sutherland (Powner et al. 2009)  shows how nature could have spontaneously assembled pyrimidine ribonucleotide monomers from prebiotically plausible molecules through intermediates that contribute atoms to both the sugar and base portions of the ribonucleotides, thus avoiding a condensation step of sugar and base altogether 3

Sutherland's research produced only 2 of the 4 RNA nucleobases, and Dr. Garner also explained why, as is often the case, the basic chemistry itself also required the hand of an intelligent chemist:

As far as being relevant to OOL, the chemistry has all of the usual problems. The starting materials are "plausibly" obtainable by abiotic means, but need to be kept isolated from one another until the right step, as Sutherland admits. One of the starting materials is a single mirror image for which there is no plausible way to get it that way abiotically. Then Sutherland ran these reactions as any organic chemist would, with pure materials under carefully controlled conditions. In general, he purified the desired products after each step, and adjusted the conditions (pH, temperature, etc.) to maximum advantage along the way. Not at all what one would expect from a lagoon of organic soup. He recognized that making of a lot of biologically problematic side products was inevitable, but found that UV light applied at the right time and for the right duration could destroy much (?) of the junk without too much damage to the desired material. Meaning, of course, that without great care little of the desired chemistry would plausibly occur. But it is more than enough for true believers in OOL to rejoice over, and, predictably, to way overstate in the press. 4

Robert Shapiro, professor emeritus of chemistry at New York University 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,' he says. According to Shapiro, it is hard to imagine RNA forming in a prebiotic world along the lines of Sutherland's synthesis.
'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,' argues Shapiro.
 5

In the book origins of life, Hugh Ross writes at  page 79 : 

Cytosine is one of the molecular components of nucleic acids (DNA and RNA), cytosine assumes an important place in both RNA-world and pre-RNA-world origin-of-life models (this posits that RNA or some RNA precursor chemically evolved before proteins and DNA). Cytosine, a pyrimidine, is a six-membered ring composed of four carbon atoms and two nitrogen atoms. Along with other ring compounds, such as adenine, guanine, thymine, and uracil, cytosine repeatedly extends from the chainlike backbone of DNA and RNA. The nitrogen-containing rings sequenced along DNA or RNA provide the chemical information that determines biochemical function. Chemists have discovered two possible pathways that produce cytosine. One route involves a reaction between cyanoacetylene and cyanate, and the other reaction begins with cyanoacetaldehyde and urea.6 These four compounds represent essential ingredients of early Earth’s supposed prebiotic soup. Chemist Robert Shapiro demonstrated, however, that the two chemical routes lack any relevance.7 He points out the unlikelihood that cyanoacetylene, cyanate, cyanoacetaldehyde, and urea existed at sufficient levels on primordial Earth to effect the production of cytosine. Even if they had occurred at appropriate levels, interfering chemical reactions would have quickly consumed these compounds before cytosine could form. Cyanoacetylene rapidly reacts with ammonia, amines, thiols, and hydrogen cyanide. Cyanate undergoes rapid reaction with water. In the presence of water, cyanoacetaldehyde decomposes into acetonitrile and formate. When cytosine does form, it rapidly decomposes. At room temperature and with a neutral pH, cytosine breaks down, losing half its molecules in 340 years. At 32 °F (0 °C), its half-life is 17,000 years—still too short a time for cytosine to be part of the supposed first self-replicator. To date, scientists have failed to produce cytosine in a spark-discharge experiment, nor has cytosine been recovered from meteorites or extraterrestrial sources. Because meteorites (and other extraterrestrial materials) serve as a proxy for early Earth’s chemistry, the absence of cytosine in these sources would seem to affirm Shapiro’s conclusion. Shapiro also critically analyzed prebiotic simulation experiments that produced the DNA and RNA component adenine. As with cytosine, he showed that adenine formation on early Earth (by currently recognized prebiotic routes) could not reasonably have occurred, for many of the same reasons. Recent work by James Cleaves and Stanley Miller uncovers an additional problem.11 Nucleobases readily react with formaldehyde and acetaldehyde, compounds most certainly present on early Earth, to form both small molecule derivatives and large intractable molecules. Even under mild conditions, these reactions take place so rapidly that they would preferentially occur at the expense of reactions that could lead to RNA. Thus, if nucleobases could form, competing reactions would likely consume them.


Prebiotic cytosine synthesis: A critical analysis and implications for the origin of life
 1

The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses. If cytosine concentrations are to be maintained on a worldwide basis, then synthesis must be sufficient to replace depletion. The syntheses described thus far do not possess the necessary speed and selectivity to meet this requirement. The use of drying lagoons as a site for prebiotic synthesis has been suggested as a remedy: synthetic rates would be enhanced by greatly increasing the concentration of the reagents. The lagoon suggestion appears geologically implausible, however. All schemes in which cytosine is synthesized locally and distributed globally also are handicapped in that the enormous dilution that takes place when cytosine is released into a global sea offsets any gain in synthetic efficiency.

Prebiotic guanine synthesis

Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA. 

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. 1
The backbone made up of (deoxy-ribose) sugar molecules

Prebiotic ribose synthesis: A critical analysis

The evidence that is currently available does not support the availability of ribose on the prebiotic earth, except perhaps for brief periods of time, in low concentration as part of a complex mixture, and under conditions unsuitable for nucleoside synthesis. 1

Sugars are very unstable, and easily decompose or react with other chemicals. This counts against any proposed mechanism to concentrate them to useable proportions. 2

Asphalt, Water, and the Prebiotic Synthesis of Ribose, Ribonucleosides, and RNA  3

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.

However, a discontinuous synthesis model is well-supported by experimental work that might produce RNA from atmospheric CO2, H2O, and N2. For example, electrical discharge in such atmospheres gives formaldehyde (HCHO) in large amounts and glycolaldehyde (HOCH2CHO) in small amounts. When rained into alkaline aquifers generated by serpentinizing rocks, these substances were undoubtedly converted to carbohydrates including ribose. Likewise, atmospherically generated HCN was undoubtedly converted in these aquifers to formamide and ammonium formate, precursors for RNA nucleobases. Finally, high reduction potentials maintained by mantle-derived rocks and minerals would allow phosphite to be present in equilibrium with phosphate, mobilizing otherwise insoluble phosphorus for the prebiotic synthesis of phosphite and phosphate esters after oxidation.

So why does the community not view this discontinuous synthesis model as compelling evidence for the RNA-first hypothesis for the origin of life? In part, the model is deficient because no experiments have joined together those steps 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.


A new chicken-and-egg paradox relating to the origin of life

http://www.uncommondescent.com/intelligent-design/do-viruses-help-explain-the-origin-of-life/

Cells could not have evolved without viruses, as they need reverse transcriptase (which is found only in viruses) in order to move from RNA to DNA.

In other words, instead of helping to solve the problem of the origin of life on Earth, recent research has only served to highlight one of its central paradoxes. And yet the science media reports the latest discoveries as if the solution is just around the corner. Don’t you find that just a little strange?

In order to move from RNA to DNA, you need an enzyme called reverse transcriptase,” Dolja said. “It’s only found in viruses like HIV, not in cells. So how could cells begin to use DNA without the help of a virus?”

https://en.wikipedia.org/wiki/Reverse_transcriptase#In_eukaryotes

Creation of double-stranded DNA occurs in the cytosol as a series of these steps:

A specific cellular tRNA acts as a primer and hybridizes to a complementary part of the virus RNA genome called the primer binding site or PBS
Complementary DNA then binds to the U5 (non-coding region) and R region (a direct repeat found at both ends of the RNA molecule) of the viral RNA
A domain on the reverse transcriptase enzyme called RNAse H degrades the 5’ end of the RNA which removes the U5 and R region
The primer then ‘jumps’ to the 3’ end of the viral genome and the newly synthesised DNA strands hybridizes to the complementary R region on the RNA
The first strand of complementary DNA (cDNA) is extended and the majority of viral RNA is degraded by RNAse H
Once the strand is completed, second strand synthesis is initiated from the viral RNA
There is then another ‘jump’ where the PBS from the second strand hybridizes with the complementary PBS on the first strand
Both strands are extended further and can be incorporated into the hosts genome by the enzyme integrase

Creation of double-stranded DNA also involves strand transfer, in which there is a translocation of short DNA product from initial RNA dependent DNA synthesis to acceptor template regions at the other end of the genome, which are later reached and processed by the reverse transcriptase for its DNA-dependent DNA activity

To date, scientists have failed to produce cytosine in a spark-discharge experiment, nor has cytosine been recovered from meteorites or extraterrestrial sources. Because meteorites (and other extraterrestrial materials) serve as a proxy for early Earth’s chemistry, the absence of cytosine in these sources would seem to affirm Shapiro’s conclusion. Shapiro also critically analyzed prebiotic simulation experiments that produced the DNA and RNA component adenine. As with cytosine, he showed that adenine formation on early Earth (by currently recognized prebiotic routes) could not reasonably have occurred, for many of the same reasons. Recent work by James Cleaves and Stanley Miller uncovers an additional problem. Nucleobases readily react with formaldehyde and acetaldehyde, compounds most certainly present on early Earth, to form both small molecule derivatives and large intractable molecules. Even under mild conditions, these reactions take place so rapidly that they would preferentially occur at the expense of reactions that could lead to RNA. Thus, if nucleobases could form, competing reactions would likely consume them.


https://books.google.com.br/books?id=rlIyVJ9dpzkC&pg=PA149&lpg=PA149&dq=thymidylate+synthase+origin+of+life&source=bl&ots=cocJIaoVZg&sig=VtlcxunaYAkxx4DZwpEjvHnh_-0&hl=en&sa=X&ei=AnyHVYyRA8qy-AG1v4HYBw&ved=0CDAQ6AEwAw#v=onepage&q=thymidylate%20synthase%20origin%20of%20life&f=false

DNA & origin of life scenarios The_ge10


Prebiotic thymine synthesis

Thymidylate synthases (Thy) are key enzymes in the synthesis of deoxythymidylate, 1 of the 4 building blocks of DNA. As such, they are essential for all DNA-based forms of life and therefore implicated in the hypothesized transition from RNA genomes to DNA genomesTwo  unrelated Thy enzymes, ThyA and ThyX, are known to catalyze the same biochemical reaction. 7 

Thymidylate synthase (Thy) is a fundamental enzyme in DNA synthesis because it catalyzes the formation of deoxythymidine 5′-monophosphate (dTMP) from deoxyuridine 5′-monophosphate (dUMP). For decades, only one family of thymidylate synthase enzymes was known, and its presence was considered necessary to maintain all DNA-based forms of life. Then, a gene encoding an alternative enzyme was discovered and characterized (Dynes and Firtel 1989; Myllykallio et al. 2002), and the novel enzyme was named ThyX, whereas the other enzyme was renamed ThyA. Even though both reactions accomplish the same  key step, the reaction mechanisms, or steps, catalyzed by the FDTS and TS enzymes are structurally different.The 2 enzymes, ThyA and ThyX, were found to have distinctly different sequences and structures, thus alluding to independent  origins.

Thats interesting, as we find two distinct enzymes with two different sequences and structures synthesizing the same reaction, thus being a example of convergence right in the beginning. How remote was the chance for this to happen by natural means , considering, that convergence does not favour naturalistic explanations ? 

as  Stephen J.Gould wrote: “…No finale can be specified at the start, none would ever occur a second time in the same way, because any pathway proceeds through thousands of improbable stages. Alter any early event, ever so slightly, and without apparent importance at the time, and evolution cascades into a radically different channel.1

Stephen J. Gould, Wonderful Life: The Burgess Shale and the Nature of History (New York, NY: W.W. Norton & Company, 1989), 51.

By virtue of their function and phyletic distribution, Thys are ancient enzymes, implying 1) the likely participation of one or both enzymes during the transition from an RNA world to a DNA world (based on protein catalysts: Joyce 2002) and 2) the probable presence of a gene encoding Thy in the genome of the common ancestors of eukaryotes, bacteria, and archaea (Penny and Poole 1999; Woese 2002; Koonin 2003; Kurland et al. 2006). Thus, tracing back the  pathway of genes encoding ThyA and ThyX may shed light on the actively debated wider issue regarding the origins of viral and cellular DNA 

This brings us to the same problem as with Ribonucleotide Reductase enzymes (RNR), which is the classic chicken and egg, catch22 situation.  ThyA and ThyX enzymes are required to make DNA. DNA is however required to make these enzymes. What came first ??  We can conclude with high certainty that this enzyme buries any RNA world fantasies, and any possibility of transition from  RNA to DNA world scenarios, since both had to come into existence at the same time. 

Further implications :  There is a third enzyme doing doing the same reaction: 

New Chemical Reaction For DNA Production In Bacteria And Viruses Discovered 6

Scientists have discovered a new chemical reaction for producing one of the four nucleotides, or building blocks, needed to build DNA. The reaction includes an unusual first step, or mechanism, and unlike other known reactions that produce the DNA building block, uses an enzyme that speeds up, or catalyzes, the reaction without bonding to any of the compounds, or substrates, in the reaction.

The chemical reaction discovered by the researchers uses an enzyme called flavin-dependent thymidylate synthase, or FDTS. The enzyme is coded by the thyX gene and has been found primarily in bacteria and viruses, including several human pathogens and biological warfare agents. 

Both the new and classical enzymatic reactions complete a key step in producing the DNA building block by adding a methyl group--one carbon atom attached to three hydrogen atoms--to the building block's precursor molecule called deoxy-uridine monophosphate, or dUMP.
DNA & origin of life scenarios New_ch10




1) http://www.pnas.org/content/96/8/4396.full
2) http://www.trueorigin.org/originoflife.php
3) http://www.talkorigins.org/faqs/abioprob/originoflife.html
4) http://www.evolutionnews.org/2009/07/scientists_say_intelligent_des022621.html
5) http://www.rsc.org/chemistryworld/News/2009/May/13050902.asp
6) http://www.sciencedaily.com/releases/2009/04/090416161133.htm
7) http://www.ncbi.nlm.nih.gov/pubmed/20525631


1) http://www.ncbi.nlm.nih.gov/pubmed/11536683?dopt=Abstract
2) Hugh Ross & Fazale Rana, Origins of life pg.79
3) http://www.pnas.org/content/104/44/17272.full

1) http://www.ncbi.nlm.nih.gov/pubmed/2453009
2) http://creationwiki.org/Origin_of_life
3) http://pubs.acs.org/doi/abs/10.1021/ar200332w

further readings :

https://www.c4id.org.uk/index.php?option=com_content&view=article&id=211:the-problem-of-the-origin-of-life&catid=50:genetics&Itemid=43

http://www.ncbi.nlm.nih.gov/books/NBK6360/figure/A43731/?report=objectonly

Metabolic pathways for RNA and DNA precursors biosynthesis: a palimpsest from the RNA to DNA world transition? The biosynthetic pathways for purine and pyrimidine nucleotides both start with ribose 5-monophosphate. The formation of the four bases requires several amino-acids, formate and carbamyl-phosphate. Nucleotide monophosphates (NMP) are converted into RNA precursors (NTP) by NMP kinases (k) and NDP kinases (K). These reactions probably are relics of the RNA-protein world. DNA precursors are produced from NDP and/or NTP by ribonucleotide reductases (RNR), except for dTTP, which results from methylation of dUMP. dTMP is produced from dUMP by Thymidylate synthases (ThyA or ThyX) and converted into dTTP by the same kinases that convert NMP into NTP. dUMP can be produced either by dUTPAse or by dCTP deaminase. In the U-DNA world, it could have been also produced by degradation of U-DNA. The mode of dTMP production clearly suggests that U-DNA was an evolutionary intermediate between RNA and T-DNA. Some viruses contain U-DNA, whereas others contain HMC-DNA (HMC= hydroxymethyl-cytosine). Transformation of C into HMC occurs at the level of dCMP, and conversion of dCMP into dHMCMP is catalyzed by a dCMP hydroxy-methyl transferase (dCMP HM transferase), which is homologue to ThyA (See refs. 11, 14, and 19 for more details).

[url=https://servimg.com/view/17307623/802][img]https://i.servimg.com/u/f18/17/30/76/23/ch314f1



Last edited by Admin on Wed Feb 27, 2019 5:47 pm; edited 1 time in total

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2DNA & origin of life scenarios Empty Re: DNA & origin of life scenarios Tue Sep 11, 2018 12:25 pm

Otangelo


Admin
DNA: Destroys the theory of Evolution. Unmasking the lies

(1) Laboratory experiments show that DNA spontaneously and progressively disintegrates over time. Estimates indicate that DNA should completely break down within 10,000 years. Any fossil DNA remaining after this period (especially more than say 100,000 years) must of necessity indicate that the method of dating the fossil is in error. Nature, Vol. 352, August 1, 1991 p:381
(2) The classic evolutionary problem of 'which came first, protein or DNA' has not been solved by the 'self-reproducing' RNA theory as many textbooks imply. The theory is not credible as it was based on laboratory simulations which were highly artificial, and were carried out with a 'great deal of help from the scientists'. Scientific American, February, 1991 p:100-109
(3) DNA can only be replicated in the presence of a specific enzyme which can only be manufactured by the already existing DNA. Each is absolutely essential for the other, and both must be present for the DNA to multiply. Therefore, DNA has to have been in existence in the beginning for life to be controlled by DNA. Scott M. Huse, "The Collapse of Evolution", Baker Book House: Grand Rapids (Michigan), 1983 p:93-94
(4) There is no natural chemical tendency for the series of base chemicals in the DNA molecule to line up a series of R-groups in the orderly way required for life to begin. Therefore being contrary to natural chemical laws, the base-R group relationship and the structure of DNA could not have formed by random chemical action. Scott M. Huse, "The Collapse of Evolution", Baker Book House: Grand Rapids (Michigan), 1983 p:94
(5) "The origin of the genetic code is the most baffling aspect of the problem of the origins of life and a major conceptual or experimental breakthrough may be needed before we can make any substantial progress." Written by biochemist Dr Leslie Orgel (Salk Institute, California) in the article "Darwinism at the Very Beginning of Life" in New Scientist, April 15, 1982 p:151
(6) Computer scientists have demonstrated that information does not, and cannot arise spontaneously. Information only results from the input of energy, under the all-important direction of intelligence. Therefore, as DNA is information, it cannot have been formed by natural chemical means. P. Moorhead & M. Kaplan (eds.), "Mathematical Challenges to the Neo-Darwinian Interpretation of Evolution", Wistar Institute: Philadelphia (Pennsylvania), 1967
(7) The transformation of one species into another by viruses transferring small sections of the DNA of another species could not cause evolution for three reasons:- (1) if genes for a particular feature or action were transmitted as a small piece of DNA, the animal would not be able to utilize the code unless it had all the other structures present to support that feature, (2) there is no guarantee that without the rest of the supporting DNA code, that the feature would appear in the right place, and (3) the information transmitted would already be in existence and would not lead to the formation of a species with totally new features. Reader's Digest, March 1980
(8 ) "A scientist who won the Nobel Prize for his discovery of the DNA technique that inspired [the film] Jurassic Park was asked how likely it was that in the future, a dinosaur could be re-created from ancient DNA trapped in amber, as in the movie. Dr Kary Mullis replied in essence that it would be more realistic to start working on a time machine to go back and catch one." From Creation Ex Nihilo, Vol. 16, No. 2, March 1994, p:8, summarizing The Salt Lake Tribune, December 5, 1993

DNA is irreducible complex

http://reasonandscience.heavenforum.org/t2093-dna-is-irreducible-complex

Individual bases : take away the sugar in the DNA backbone = no function
Take away the phosphate in the backbone = no function
Take away the nucleic acid bases = no function
Evolution is not a driving force at this stage, since replication of the cell depends on DNA.
So the individual DNA molecules are irreducible complex
DNA in general ( the double helix )
Unless the two types, purines, and pyrimidines are present, and so the individual four bases = no function, and no hability of information storage
The enzymes and proteins for assembly and synthesis of the DNA structure must also be present, otherwise, no DNA double helix......

Origin of the DNA deoxyribonucleic acid  double helix

http://reasonandscience.heavenforum.org/t2028-origin-of-the-dna-double-helix

Self-organizing biochemical cycles 1

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18793/

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.




The DNA story



Like RNA, deoxyribonucleic acid (DNA) is a linear polymer of nucleotides. Each nucleotide consists of a pentose sugar, a nitrogenous base and a phosphate group. The sugar–phosphate linkages form an external backbone with the bases sticking in and hydrogen-bonding with complementary bases of the opposite sugar–phosphate backbone, zipper-fashion, producing the famous double helix structure of DNA. The helix can take on alternate forms in which it twists to alter the compactness of its spiral and bends to change its overall shape. The packing of DNA in a microscopically visible chromosome represents a 10,000-fold shortening of its actual length. Little is known of the structure of DNA in the natural state within the cell. Clearly it is dynamic, and by assuming different forms DNA controls various biological processes such as replication, transcription and recombination. This is a fruitful area for research.



The Synthesis of β-d-Ribose



The abiotic origin of DNA is beset with problems similar to those seen with RNA.48 The synthesis of deoxyribose forms the nub. We have already mentioned the difficult synthesis of even small amounts of β-d-ribose for the in vitroproduction of RNA. Furthermore, we might have expected deoxyribonucleotides to be biosynthesised de novo from deoxyribose precursors. In real life, however, DNA components (the deoxyribonucleotides dADP, dCDP, dGDP and dUDP) are synthesised from their corresponding ribonucleotides by the reduction of the C2' position. The enzymes that do this are named ribonucleotide reductases. There are three main classes of reductases. All replace the 2'-OH group of ribose via some elegant free radical mechanisms.49,50 The class III anaerobic Escherichia coli reductase is thought to be the most closely related to the common reductase ancestor from which the three main classes are presumed to have evolved. It has been proposed that the pristine reductase enzyme, similar to present-day class III enzymes, arose before the advent of photosynthesis and therefore before the appearance of oxygen. Now the E. coli class III enzyme mentioned above can be induced by culturing the bacteria under anaerobic conditions. This enzyme is an Fe-S protein that in its active form contains an oxygen-sensitive glycyl free radical.51


This poses a conundrum: the survival and continual evolution of an oxygen-sensitive enzyme when oxygen appeared. On the other hand, the class I reductases require oxygen for free radical generation. Surely they could not have evolved and operated in the anaerobic first cell in an oxygen-free environment.52 Moreover, one of the most remarkable aspects of this E. coli ribonucleotide class I reductase is its ability to maintain its highly reactive free radical state for a long period. Interestingly, this is achieved in vivo by internally generated oxygen. Four proteins have to be in place:

Flavin oxidoreductase, which releases superoxide ion (O2–),
Superoxide dismutase, to rapidly convert this destructive radical to H2O2 and O2,
A catalase, to disproportionate H2O2 to H2O and O2, and
A fourth protein, thioredoxin, that functions as a reductant.

The oxygen oxidises Fe II and a deeply buried tyrosyl residue (Tyr122). Herein lies a difficulty. The reductases are complex protein reaction centres acting in tandem on each other and on the 2'-OH group of ribose. These must all have co-evolved before DNA and along with RNA. Could this be seriously contemplated for a metabolically naive RNA “progenote”?
The origins of deoxyribose and of DNA therefore remain unsolved mysteries.


Even if the DNA molecule were assembled abiotically, there is the instability and decay of the polymer by hydrolysis of the glycosyl bonds and the hydrolytic deamination of the bases.53 Each human cell turns over 2,000–10,000 DNA purine bases every day owing to hydrolytic depurination and subsequent repair. Genetic information can be stored stably only because a battery of DNA repair enzymes scan the DNA and replace the damaged nucleotides. Without these enzymes it would be inconceivable how primitive cells kept abreast of the constant high-level damage by the environment and by endogenous reactions. If unrepaired, cell death would result. Indeed, the spontaneous errors resulting from intrinsic DNA instability are usually many times more dangerous than chance injuries from environmental causes.54 The enzymes of the DNA repair system are a marvel in themselves and have been rightfully recognised as such.55 Reports of the culture of Bacillus sphaericus from spores preserved in amber for over “25 million years” does not tally with what is known of the physico-chemical properties of DNA.56


Several DNA Paradoxes


The total amount of DNA in the haploid genome is its C-value. Intuitively we would expect that there should be a relationship between the complexity of an organism and the amount of its DNA. The failure to consistently correlate the total amount of DNA in a genome with the genetic and morphological complexity of the organism is called the C-value paradox.57 This paradox manifests itself in three ways. Many plant species have from two to ten times more DNA per cell than the human cell. Among the vertebrates with the greatest amount of DNA are the amphibians. Salamander cells contain 10–100 times more DNA than mammalian cells. It is hard to make sense of the existence of such major redundancies in organisms evolutionarily less complex than man.There is also considerable intragroup variation in DNA content where morphology does not vary much. For example, the broad bean contains about three to four times as much DNA per cell as the kidney bean. Variations of up to 100 times are found among insects and among amphibians. In other words, cellular DNA content does not correlate with phylogeny.Large stretches of DNA in the genome, say, of humans, appear to have no demonstrable function. This will be discussed later.


http://creation.com/origin-of-life-critique

1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18793/


Scientists discover new clue to chemical origins of life

"We are trying to understand the chemical origins of life. One of the interesting questions is where carbohydrates come from because they are the building blocks of DNA and RNA. What we have achieved is the first step on that pathway to show how simple sugars -- threose and erythrose -- originated. We generated these sugars from a very simple set of materials that most scientists believe were around at the time that life began."

Do you want a clear picture of origins? 

Don't listen to Dawkins, Krauss, Dennet, Harris, Sagan, and their philosophy. 
Don't listen to Gould about fossils 
Don't listen to Darwin about evolution

Forget evolution. Forget fossil comparisons. 

Ask how the building blocks of life on earth could have emerged
Ask how they could have come together to form the most complex factory on earth
Ask how the information systems could have emerged : 

----- >>> without evolution !!! and 
----- >>> without chemical reactions having to follow physical constraints and routes. 

Prior when life began, there was no evolution, nor physical necessity. 

ONLY a) ------>>>> unguided, random, lucky accidents , or 
b) ------>>>> design. 

With this in mind, consider the

1.https://www.sciencedaily.com/releases/2012/01/120124092930.htm

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3DNA & origin of life scenarios Empty Re: DNA & origin of life scenarios Tue Sep 11, 2018 12:27 pm

Otangelo


Admin
Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions 1

Although the issue of temporally separated supplies of glycolaldehyde and glyceraldehyde remains a problem, a number of situations could have arisen that would result in the conditions of

heating 
progressive dehydration  
cooling, 
rehydration
ultraviolet irradiation

that seems already a quite elaborate synthesis process, requiring five manufacturing steps. 

1. Why would a prebiotic earth go through such a process? 
2. It would have to be repeated in a huge number to produce enough compounds, ready to start interacting one with the other.

Further problems:

3.The starting materials are “plausibly” obtainable by abiotic means, but need to be kept isolated from one another until the right step, as Sutherland admits.
4. One of the starting materials is a single mirror image for which there is no plausible way to get it that way abiotically.
5. Sutherland ran these reactions as any organic chemist would, with pure materials under carefully controlled conditions.
6. In general, he purified the desired products after each step and adjusted the conditions (pH, temperature, etc.) to maximum advantage along the way.
7. Without oxygen on earth, UV light would readily destroy the compounds.
8. They used pH manipulation, phosphate buffers and irradiation all at the correct times and amounts to achieve their goal, which was to produce “activated pyrimidine ribonucleotides.”
9. Certainly, intelligent guidance was all over to find the right pathway to the desired goal.
10. They used a high concentration of phosphate. Life in the modern ocean is phosphate limited as phosphate is generally about 0.5 micro-molar at the sea surface and only 2-4 micro-molar at depth.

However, Robert Shapiro, professor emeritus of chemistry at New York University 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,’ he says. According to Shapiro, it is hard to imagine RNA forming in a prebiotic world along the lines of Sutherland’s synthesis.‘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,’ argues Shapiro. Instead, he advocates the metabolism-first argument: that early self-sustaining autocatalytic chemosynthetic systems associated with amino acids predated RNA.
(Robert Shapiro quoted in James Urquhart, Insight into RNA origins, Royal Society of Chemistry (May 13, 2009).)


DNA & origin of life scenarios Pyrimi14
DNA & origin of life scenarios Pyrimi12
DNA & origin of life scenarios Pyrimi15
DNA & origin of life scenarios Pyrimi11
DNA & origin of life scenarios Pyrimi16
DNA & origin of life scenarios Pyrimi10
DNA & origin of life scenarios U2jYSqi

1. https://sci-hub.bz/https://www.nature.com/nature/journal/v459/n7244/full/nature08013.html
2. https://evolutionnews.org/2009/07/scientists_say_intelligent_des/

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4DNA & origin of life scenarios Empty Re: DNA & origin of life scenarios Tue Sep 11, 2018 12:27 pm

Otangelo


Admin
There is a unbridgeable gap between origin of life proposals, and the complexity of the biochemical processes in the cell to synthesize the building blocks for life.

http://reasonandscience.heavenforum.org/t1362-panspermia-not-a-viable-explanation-for-the-ool#3222

DNA & origin of life scenarios M8dNXx5

The amazing complexity to make DNA nucleobases

http://reasonandscience.heavenforum.org/t2028-origin-of-the-dna-double-helix#3426

Both nucleobases, Pyrimidines, and Purines had to begin to be produced prior when life began since they make up DNA - the molecule that stores genetic information. That means as well, that all enzymes used in the pathway to make the bases had to be present prior the supposed Last Universal Common Ancestor ( that's a fairy tale anyway, but for the argument, it doesn't matter )  For pyrimidines, six synthesis manufacturing/biosynthesis steps are required, and for purines, eleven. 

The thrilling part is that just one of all these enzymes is staggeringly complex. David Goodsell writes: Aspartate carbamoyltransferase is fully as complex as any fine automobile in our familiar world. 

Take just a moment to ponder the immensity of this enzyme. The entire complex is composed of over 40,000 atoms, each of which plays a vital role. The handful of atoms that actually perform the chemical reaction are the central players. But they are not the only important atoms within the enzyme--every atom plays a supporting part. The atoms lining the surfaces between subunits are chosen to complement one another exactly, to orchestrate the shifting regulatory motions. The atoms covering the surface are carefully picked to interact optimally with water, ensuring that the enzyme doesn't form a pasty aggregate, but remains an individual, floating factory. And the thousands of interior atoms are chosen to fit like a jigsaw puzzle, interlocking into a sturdy framework. Aspartate carbamoyltransferase is fully as complex as any fine automobile in our familiar world. And, just as manufacturers invest a great deal of research and time into the design of an automobile, enzymes like aspartate carbamoyltransferase are finely tuned.

Beside this enzyme, all others, almost 20, had to be produced prebiotically, and then interconnected like in a factory assembly line, to make DNA nucleobases !! 

There was no evolution. No natural selection. No mutations - nah nah  Charly won't provide the crutches to explain the feat.....

The only alternative to these biochemical processes would be, that the basic building blocks were readily available on a prebiotic earth. Glycine for instance is a indispensable substrate for pyrimidine nucleotide synthesis, and so - DNA - in cells. It  requires at least 5 biosynthetic steps and the respective enzymes to be synthesized. In a prebiotic earth, the only alternative would have been that glycine came from comets.

Comet contains glycine, key part of recipe for life 3
May 27, 2016
An important amino acid called glycine has been detected in a comet for the first time, supporting the theory that these cosmic bodies delivered the ingredients for life on Earth, researchers said Friday.
In addition to the simple amino acid glycine, the instrument also found phosphorus. The two are key components of DNA and cell membranes. "Demonstrating that comets are reservoirs of primitive material in the Solar System, and vessels that could have transported these vital ingredients to Earth, is one of the key goals of the Rosetta mission, and we are delighted with this result."

Panspermia, not a viable explanation for the OOL
http://reasonandscience.heavenforum.org/t1362-panspermia#1926

Chemistry happens, and interesting molecules form in space; so what?  It’s not going to help the believers in naturalistic origin of life.  So they found glycine, the simplest and only non-chiral amino acid.  The biologists told the astronomers to look for life’s building blocks in space, because they were having such a hard time producing them on Earth.  They would need megatons of amino acids and nucleic acid bases to rain down on the Earth for any hope of getting successful concentrations, but then the precious cargo would be subject to rapid degradation by water, oxygen, UV light, and harmful cross-reactions.  Even then, they would be mixtures of left and right handed forms, with no desire nor power to organize themselves into astronomers who could invent weird science like this.
.
Following the unresolved issues of nucleotide biosynthesis
http://reasonandscience.heavenforum.org/t2028-biosynthesis-of-the-dna-double-helix-evidence-of-design#3426

Glycine
http://reasonandscience.heavenforum.org/t1740-origin-of-the-canonical-twenty-amino-acids-required-for-life#5731

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5DNA & origin of life scenarios Empty Re: DNA & origin of life scenarios Tue Sep 11, 2018 12:28 pm

Otangelo


Admin
Prebiotic Nucleic Acid synthesis

The same year that Miller published his pioneering result regarding abiotic amino acid synthesis, the double-helical model for the structure of DNA was published (Watson and Crick 1953), which effectively clinched the role of nucleic acids in the inheritance of biological mutations. There are two types of nucleic acids important in biological systems, DNA and RNA, linked by the processes of transcription and biosynthesis
(Figure 5.1).

DNA & origin of life scenarios CRwx09H


Not long after Miller’s and Watson and Crick’s discoveries, the search for abiotic mechanisms for the synthesis of these important biochemicals began. Oró and Kimball showed that adenine, a biological purine, could be derived from the polymerization of aqueous HCN, of which it is formally a pentamer (C5H5N5) (Oró and Kimball 1961). The mechanism of this synthesis was soon elucidated, and shortly thereafter, syntheses of other important purines including guanine, and the biosynthetic precursor's xanthine and hypoxanthine were elaborated (Ferris and Orgel 1965, 1966) (Figure 5.11).

Divergent prebiotic synthesis of pyrimidine and 8-oxo-purine ribonucleotides 19
Understanding prebiotic nucleotide synthesis is a long-standing challenge thought to be essential to elucidate the origins of life on Earth. Recently, remarkable progress has been made, but to date all proposed syntheses account separately for the pyrimidine and purine ribonucleotides; no divergent synthesis from common precursors has been proposed. Moreover, the prebiotic syntheses of pyrimidine and purine nucleotides that have been demonstrated operate under mutually incompatible conditions. Our results suggest that further investigation of the informational and functional properties of the 8-oxo-purine ribonucleotides is warranted.

Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions 20
At some stage in the origin of life, an informational polymer must have arisen by purely chemical means. According to one version of the ‘RNA world’ hypothesis this polymer was RNA, but attempts to provide experimental support for this have failed. In particular, although there has been some success demonstrating that ‘activated’ ribonucleotides can polymerize to form RNA, it is far from obvious how such ribonucleotides could have formed from their constituent parts (ribose and nucleobases). Ribose is difficult to form selectively, and the addition of nucleobases to ribose is inefficient in the case of purines and does not occur at all in the case of the canonical pyrimidines. Although the issue of temporally separated supplies of glycolaldehyde and glyceraldehyde remains a problem, a number of situations could have arisen that would result in the conditions of heating and progressive dehydration followed by cooling, rehydration and ultraviolet irradiation.

Cytosine
Cytosine  is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA).

Dozens of enzymes are needed to make the DNA bases cytosine and thymine from their component atoms. 5 The first step is a "condensation" reaction, connecting two short molecules to form one longer chain, performed by  Aspartate carbamoyltransferase. Other enzymes then connect the ends of this chain to form the six-sided ring of nucleotide bases, and half a dozen others shuffle atoms around to form each of the bases.

In bacteria, the first enzyme in the sequence, aspartate carbamoyltransferase, controls the entire pathway. (In human cells, the regulation is more complex, involving the interaction of several of the enzymes in the pathway.) Bacterial aspartate carbamoyltransferase determines when thymine and cytosine will be made, through a battle of opposing forces. It is an allosteric enzyme, referring to its remarkable changes in shape (the term is derived from the Greek for "other shape"). The enzyme is composed of six large catalytic subunits and six smaller regulatory subunits.

The active site of the enzyme is located where two individual catalytic subunits touch, so the position of the two subunits relative to one another is critical. If the two subunits are in tight contact, an amino acid from one extends into the active site of the other, blocking its action. If the two are pulled slightly apart, however, the active sites are revealed, allowing molecules to enter and the reaction to be performed. This is the job of the regulatory subunits: they alternately pull the central catalytic subunits apart, turning the enzyme on, or allow them to stick together,  turning the entire complex off. 

Take just a moment to ponder the immensity of this enzyme. The entire complex is composed of over 40,000 atoms, each of which plays a vital role. The handful of atoms that actually perform the chemical reaction are the central players. But they are not the only important atoms within the enzyme--every atom plays a supporting part. The atoms lining the surfaces between subunits are chosen to complement one another exactly, to orchestrate
the shifting regulatory motions. The atoms covering the surface are carefully picked to interact optimally with water, ensuring that the enzyme doesn't form a pasty aggregate, but remains an individual, floating factory. And the thousands of interior atoms are chosen to fit like a jigsaw puzzle, interlocking into a sturdy framework. Aspartate carbamoyltransferase is fully as complex as any fine automobile in our familiar world. And, just as manufacturers invest a great deal of research and time into the design of an automobile, enzymes like aspartate carbamoyltransferase are finely tuned.

Prebiotic synthesis
Regardless, a few assumptions on substrate availability in the prebiotic earth, have led to questions of what is possible in terms of generating usable building blocks leading to nucleic acids. Most studies have focused on:

(1) the prebiotic synthesis of the pyrimidine and purine bases;
(2) the synthesis of ribose;
(3) connecting the two to make nucleosides and nucleotides; and, lastly,
(4) the formation of long enough polymers to give rise to catalytically active RNA and finally tRNAs  8




1. ASTROBIOLOGY An Evolutionary Approach, page 103

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6DNA & origin of life scenarios Empty Re: DNA & origin of life scenarios Tue Sep 11, 2018 12:28 pm

Otangelo


Admin
DNA synthesis - what came first, the enzymes to make DNA, or DNA to make the enzymes that synthesize DNA?

These are some enzyme names of de novo Purine and Pyrimidine biosynthesis, essential to make DNA, and supposedly extant at LUCA ( last universal common ancestor )

to make purines:

The enzymes of de novo purine synthesis

Phosphoribosyl-pyrophosphate synthetase (Prs) 

1. Ribose-phosphate diphosphokinase
2. amidophosphoribosyl transferase
3. Phosphoribosylglycinamide formyltransferase ( GAR )
4. Phosphoribosylaminoimidazole carboxylase
5. Dihydrofolate reductase
6. AIR synthetase
7. AIR carboxylase
8. SAICAR synthetase
9. adenylosuccinase (adenylosuccinate lyase)
10. AICAR transformylase
11. IMP cyclohydrolase 

The enzymes for Adenine synthesis

1. Adenylosuccinate synthase 
2. adenylosuccinase (adenylosuccinate lyase)

The enzymes for Guanine synthesis

1. IMP dehydrogenase
2. GMP synthase 

Enzymes used to make Pyrimidines

1. Carbamoyl phosphate synthase II
2. Aspartate carbamoyltransferase
3. Dihydroorotase
4. Dihydro Orotate Dehydrogenase
5. Orotate Phosphoribosyl transferase
6. Orotidine 5'-phosphate decarboxylase
7. Nucleoside-phosphate kinase  & Nucleoside-diphosphate kinase

How did these enzymes emerge on a prebiotic earth ???

It takes DNA to make these enzymes. And it takes these enzymes to make DNA.......

But there is more.

What came first, ATP or the enzymes that use ATP, to make ATP ?

1. ATP drives proteins that make Adenosine monophosphate ( AMP ). 
2. ATP drives enzymes that make Adenosine diphosphate (ADP). 
3. ATP drives enzymes that make Adenosine triphosphate (ATP). ==>> return to 1.
1. ATP drives proteins that make Adenosine monophosphate ( AMP ). 
2. ATP drives enzymes that make Adenosine diphosphate (ADP). 
3. ATP drives enzymes that make Adenosine triphosphate (ATP).
====>>> endless loop.

The Adenine triphosphate (ATP) molecule as energy source is required to drive the enzymes/protein machines that make the adenine nucleic base and adenosine monophosphate AMP, used in DNA, one of the four genetic nucleotides "letters" to write the Genetic Code, and then, using these nucleotides as starting material, then further molecular machines attach other two phosphates and produce adenine triphosphates (ATP) - the very own molecule which is used as energy source to drive the whole process.. What came first: the enzymes to make ATP, or ATP to make the enzymes that make ATP?

But lets suppose abiogenesis would produce RNA on a prebiotic earth, and so, AMP, ADP, and ATP. How could there be a transition of monomers to polyperisation ?

THE RNA WORLD,  AND THE ORIGINS OF LIFE
https://reasonandscience.catsboard.com/t2024-the-rna-world-and-the-origins-of-life

The RNA world hypothesis, to be true, has to overcome  major hurdles:

1. Life uses only right-handed RNA and DNA. The homochirality problem is unsolved. This is an “intractable problem” for chemical evolution
2. 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. 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.   In chemistry, when free energy is applied to organic matter without Darwinian evolution, the matter devolves to become more and more “asphaltic”, as the atoms in the mixture are rearranged to give ever more molecular species. In the resulting “asphaltization”, what was life comes to display fewer and fewer characteristics of life.
3. Systems of interconnected software and hardware like in the cell are irreducibly complex and interdependent. There is no reason for information processing machinery to exist without the software and vice versa.
4. A certain minimum level of complexity is required to make self-replication possible at all; high-fidelity replication requires additional functionalities that need even more information to be encoded
5.  RNA catalysts would have had to copy multiple sets of RNA blueprints nearly as accurately as do modern-day enzymes
6.  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 impossible.
7. Not one self-replicating RNA has emerged to date from quadrillions (10^24) of artificially synthesized, random RNA sequences.  
8. Over time, organic molecules break apart as fast as they form
9. How could and would random events attach a phosphate group to the right position of a ribose molecule to provide the necessary chemical activity? And how would non-guided random events be able to attach the nucleic bases to the ribose?  The coupling of a ribose with a nucleotide is the first step to form RNA, and even those engrossed in prebiotic research have difficulty envisioning that process, especially for purines and pyrimidines.”
10.  L. E. Orgel:  The myth of a self-replicating RNA molecule that arose de novo from a soup of random polynucleotides. Not only is such a notion unrealistic in light of our current understanding of prebiotic chemistry, but it should strain the credulity of even an optimist's view of RNA's catalytic potential.
11. Macromolecules do not spontaneously combine to form macromolecules
125. The transition from RNA to DNA is an unsolved problem. 
13. To go from a self-replicating RNA molecule to a self-replicating cell is like to go from a house building block to a fully build house. 
14. If two amino acids are located within the peptidyl transferase center, they will easily form a peptide bond. But as soon as you do that in the absence of the ribosome, the ends of the amino acids come together, forming a cyclic structure. Polymers cannot form. But if the ends are kept apart, by a theoretical primitive ribosome, a chain of peptide bonds could grow into a polymer. 30
15. Arguably one of the most outstanding problems in understanding the progress of early life is the transition from the RNA world to the modern protein based world. 31 
16. It is thought that the boron minerals needed to form RNA from pre-biotic soups were not available on early Earth in sufficient quantity, and the molybdenum minerals were not available in the correct chemical form. 33

Proponents of the RNA world hypothesis commonly argue that it has been proven that RNA's could self-replicate. Let's suppose that were true, that is as if self-replication could produce a hard drive. To go from a hard drive ( which by itself requires complex information to be assembled, in case of biology, DNA, not RNA since it's too unstable, ) that does not explain the origin of the information to make all life essential parts in the cell.
It is as to go just from a hard drive storage device to a self replicating factory with the ability of self replication of the entire factory once ready, to respond to changing environmental demands and regulate its metabolic pathways, regulate and coordinate all cellular processes, such as molecule and building block biosynthesis according to the cells demands, depending on growth, and other factors.
The ability of uptake of nutrients, to be structured, internally compartmentalized and organized, being able to check replication errors and minimize them, and react to stimuli, and changing environments. That's is, the ability to adapt to the environment is a must right from the beginning. If just ONE single protein or enzyme - of many - is missing, no life. If topoisomerase II or helicase are missing - no replication - no perpetuation of life.
Why would a prebiotic soup or hydrothermal vents produce these proteins - if by their own there is no use for them?

chemist Wilhelm Huck, professor at Radboud University Nijmegen
A working cell is more than the sum of its parts. "A functioning cell must be entirely correct at once, in all its complexity
http://www.ru.nl/english/@893712/protocells-formed/

The cell is irreducibly complex
https://reasonandscience.catsboard.com/t1299-the-cell-is-irreducibly-complex

ATP: The  Energy  Currency for the Cell
https://reasonandscience.catsboard.com/t2137-atp-the-energy-currency-for-the-cell

Purines and their synthesis
https://reasonandscience.catsboard.com/t2028-the-dna-double-helix-evidence-of-design#3427

Biosynthesis of the DNA double helix, evidence of design
https://reasonandscience.catsboard.com/t2028-biosynthesis-of-the-dna-double-helix-evidence-of-design

=================================================================================================================

Biosynthesis of the DNA double helix, evidence of design
https://reasonandscience.catsboard.com/t2028-biosynthesis-of-the-dna-double-helix-evidence-of-design

DNA is crucial for life. Not many however grasp how complex it is for cells to synthesize DNA molecules. To make Purines it takes a biosynthesis pathway of five enzymes, and Pyrimidines, seven.
Now let's have a closer look at just one of the enzymes to make pyrimidines, the first in the pathway, namely  Aspartate Carbamoyltransferase.

David Goodsell writes in his book: Our molecular nature, on page 26:

Dozens of enzymes are needed to make the DNA bases cytosine and thymine from their component atoms. The first step is performed by aspartate carbamoyltransferase.  In bacteria, this enzyme controls the entire pathway. (In human cells, the regulation is more complex, involving the interaction of several of the enzymes in the pathway.) The enzyme is composed of six large catalytic subunits and six smaller regulatory subunits. The active site of the enzyme is located where two individual catalytic subunits touch, so the position of the two subunits relative to one another is critical. Take just a moment to ponder the immensity of this enzyme. The entire complex is composed of over 40,000 atoms, each of which plays a vital role. The handful of atoms that actually perform the chemical reaction are the central players. But they are not the only important atoms within the enzyme--every atom plays a supporting pan. The atoms lining the surfaces between subunits are chosen to complement one another exactly, to orchestrate the shifting regulatory motions. The atoms covering the surface are carefully picked to interact optimally with water, ensuring that the enzyme doesn't form a pasty aggregate, but remains an individual, noating factory. And the thousands of interior atoms are chosen to fit like a jigsaw puzzle, interlocking into a sturdy framework. Aspartate carbamoyltransferase is fully as complex as any fine automobile in our familiar world.

This is the description of just ONE enzyme.

Now consider that : A minimal estimate for the gene content of the last universal common ancestor
19 December 2005
A truly minimal estimate of the gene content of the last universal common ancestor, obtained by three different tree construction methods and the inclusion or not of eukaryotes (in total, there are 669 ortholog families distributed in 561 functional annotation descriptions, including 52 which remain uncharacterized).

This means, and least 561 protein subunits, cofactors, apo-proteins and protein complexes are required to get a minimal proteome and functioning cell. Most of these proteins are more complex than the described above, and true factories in their own rights, such as the Ribosome, described as one of the most complex proteins known, and crucial for protein synthesis.

We know empirically, that intelligence can and does invent, elaborates, projects, and makes blueprints of complex machines, production lines, and factories, and is capable of implementing them. We do have no example of any alternative causal mechanism able of the same feat. Denton describes biological cells as " veritable micro-miniaturized factories containing thousands of exquisitely designed pieces of intricate molecular machinery, made up altogether of one hundred thousand million atoms, far more complicated than any machine built by man and absolutely without parallel in the non-living world ".

More:
Biosynthesis of the DNA double helix, evidence of design
https://reasonandscience.catsboard.com/t2028-biosynthesis-of-the-dna-double-helix-evidence-of-design

LUCA—The Last Universal Common Ancestor
The last universal common ancestor represents the primordial cellular organism from which diversified life was derived
https://reasonandscience.catsboard.com/t2176-lucathe-last-universal-common-ancestor#3995

The Cell is  a Factory
https://reasonandscience.catsboard.com/t2245-the-cell-is-a-factory

The possible mechanisms to explain the origin of life
https://reasonandscience.catsboard.com/t2515-the-possible-mechanisms-to-explain-the-origin-of-life

Neither Evolution nor physical necessity are a driving force prior dna replication. The only two alternatives to explain the origin of life, and biological cells,  are either 

a) creation by an intelligent agency, or 
b) Random, unguided, undirected natural events by a lucky "accident".

=============================================

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7DNA & origin of life scenarios Empty Re: DNA & origin of life scenarios Tue Sep 11, 2018 12:30 pm

Otangelo


Admin
1. An electron is transferred from a cysteine residue on R1 to a tyrosine radical on R2, generating a highly reactive cysteine thiyl radical. 2. This radical abstracts a hydrogen atom from C-3′ of the ribose unit. 3. The radical at C-3′ causes the removal of the hydroxide ion from the C-2′ carbon atom. Combined with a hydrogen atom from a second cysteine residue, the hydroxide ion is eliminated as water. 4. A hydroxide ion is transferred from a third cysteine residue. 5. The C-3′ radical recaptures the originally abstracted hydrogen atom. 6. An electron is transferred from R2 to reduce the thiyl radical. The deoxyribonucleotide is free to leave R1. The disulfide formed in the active site must be reduced to begin another reaction cycle.

DNA & origin of life scenarios Sem_ty21

DNA is the genetic material in all cellular organisms plus many viruses. DNA’s building blocks, deoxyribonucleotides (dNTPs), are always synthesized by reduction of ribonucleotides (either NTPs or NDPs), the building blocks of RNA. 6






DNA & origin of life scenarios Pharma10

DNA & origin of life scenarios Life_f11  9

DNA & origin of life scenarios Ribonu10

Biosynthesis or RNR enzymes

In this study, we report our findings for two temperature-conditional Chl-deficient rice mutants, v3 and st1, which harbor mutations in the open reading frames (ORFs) of the V3 and St1 genes that encode the large and small subunits of ribonucleotide reductase (RNR), respectively. RNR is an essential enzyme for DNA replication and damage repair in all living organisms, because it provides the DNA precursors by catalyzing the de novo synthesis of deoxyribonucleotide diphosphates from their corresponding ribonucleotide diphosphates 10

Ribonucleotide reductases and thymidylate synthases are encoded in all cellular genomes and in the genomes of many DNA viruses. 11

The first ribonucleotide reductases and thymidylate synthases were thus made by ancestral ribosomes containing both RNA and proteins and that were capable to perform already accurate translation. The RNA to DNA transition thus should have occurred in a complex cellular environment suitable for the production of these enzymes. This environment had to be elaborated enough to support the entire metabolism for the production of RNA precursors (rNTPs), including mechanisms for energy production. Hence, the cellular environment in which DNA finally emerged was not as “simple” as sometimes imagined, but was certainly populated by elaborated cells and viruses with an already complex metabolic network and well-organized membrane systems.

That means: It takes a complex DNA world to make DNA.....


DNA & origin of life scenarios Dna_su10


Cell survival depends on having a plentiful and balanced pool of the four chemical building blocks that make up DNA. However, if too many of these components pile up, or if their usual ratio is disrupted, that can be deadly for the cell. Chemists have discovered how a single enzyme maintains a cell's pool of DNA building blocks. 12

DNA & origin of life scenarios SCiWMRl
DNA & origin of life scenarios IytkfPC
DNA & origin of life scenarios OcOvWUf
DNA & origin of life scenarios YqfhuS3

1) http://en.wikipedia.org/wiki/Ribonucleotide_reductase
2) http://journal.frontiersin.org/article/10.3389/fcimb.2014.00052/abstract
3) 
4) 
5) http://www.nature.com/nsmb/journal/v18/n3/full/nsmb0311-251.html
6) file:///E:/Downloads/life-05-00604-v2.pdf
7) file:///E:/Downloads/fcimb-04-00052.pdf
8 ) http://ac.els-cdn.com/S0969212696001128/1-s2.0-S0969212696001128-main.pdf?_tid=c961a940-0289-11e5-82eb-00000aacb35f&acdnat=1432522831_8571d89fe458862e512f4f821993f918
9 ) http://www.mdpi.com/2075-1729/5/1/604/htm

11) http://www.ncbi.nlm.nih.gov/books/NBK6338/
12) http://www.sciencedaily.com/releases/2016/01/160112125415.htm
13. http://www.sciencedaily.com/releases/2016/01/160112125415.htm

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8DNA & origin of life scenarios Empty Re: DNA & origin of life scenarios Tue Sep 11, 2018 12:30 pm

Otangelo


Admin
BIOSYNTHESIS AND REPAIR OF METALLOCOFACTORS 20
The cofactors of many metalloproteins are likely generated by defined biosynthetic pathways. Metals are transferred in their reduced state to facilitate ligand exchange between protein factors. Specific protein factors include a metal insertase or chaperone to deliver the metal, specific redox proteins such as flavodoxins or ferredoxins that control the oxidation state of the metal, and GTPases or ATPases involved in protein unfolding/refolding to allow metal entrance into deeply buried active sites. There is  a hierarchy of metal delivery to proteins. Compartmentalization (e.g., periplasm versus cytosol in prokaryotes) and relative affinities of protein coordination environments for various metals in relation to the intracellular concentrations of those metals likely contribute to prevention of mismetallation. Many proteins are never isolated from their native source but instead from heterologous expression systems, often leading to insertion of incorrect metals. Because the “gold standard” of activity is unknown, low activity associated with incorrect clusters may go unrecognized. Metal clusters can become damaged by oxidants such as NO and O2•−, and specific pathways are implicated in their repair. Finally, during changes of oxidation state, ligands to the metal (e.g., His, Asp, Glu, and waters) can reorganize readily; structural rearrangements of carboxylate ligands (“carboxylate shifts”) are often critical to the cluster assembly process, and protons are often required for metal oxidation.

Evolution of Ribonucleotide Reductases
According to an article published in Science Magazine in 1993:
Probably the ability to reduce ribonucleotides had to exist at a time when both RNA and protein existed and before the appearance of DNA. 29

How and when ribonucleotide reduction evolved is a question that is intimately associated with the transition from the RNA world to the modern RNA + protein + DNA world, since it is the only known de novo mechanism for dNTP synthesis. The maintenance of life on Earth depends on the ability to reproduce. Reproduction requires an accurate and stable storage system for the genetic information in all organisms, including viruses. It has been recently suggested that the RNA molecule, with autoreplicative capacity, is the primary primitive molecule for the genetic information storage. Despite the wide acceptance of this idea, there are arguments against the concept of an RNA world that cannot be underestimated. 

Today, three different RNR classes have been described, with little apparent similarity between them in terms of primary protein sequence (approximately 10–20% similarity). Thus, it could be assumed that each RNR class appeared independently from each other over time. 37

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9DNA & origin of life scenarios Empty Re: DNA & origin of life scenarios Tue Sep 11, 2018 12:31 pm

Otangelo


Admin
DNA & origin of life scenarios RAqiUgd
(a) The dCMP deaminase reaction. 
(b) Trimeric dCMP deaminase. Each chain has a bound dCTP molecule (purple) and a Mg21 ion (orange)

dCMP deaminase provides a second point for allosteric regulation of deoxynucleotide triphosphate (dNTP) synthesis; it is allosterically activated by deoxycytidine triphosphate (dCTP) and feedback-inhibited by deoxythymidine triphosphate (dTTP). Of the four dNTPs, only dCTP does not interact with either of the regulatory sites on ribonucleotide reductase. Instead, it acts upon dCMP deaminase.

EnzymeProductDescription
carbamoyl phosphate synthetase IIcarbamoyl phosphateThis is the regulated step in the pyrimidine biosynthesis.
aspartic transcarbamolyase (aspartate carbamoyl transferase)carbamoyl aspartic acid-
dihhydroorotasedihydroorotateDehydration
dihydroorotate dehydrogenase(the only mitochondrial enzyme)orotateDihydroorotate then enters the mitochondria where it is oxidised through removal of hydrogens. This is the only mitochondrial step in nucleotide rings biosynthesis.
orotate phosphoribosyltransferaseOMPPRPP is used.
OMP decarboxylaseUMPDecarboxylation
uridine-cytidine kinase 2UDPPhosphorylation. ATP is used.
nucleoside diphosphate kinaseuridine 5'-triphosphate(UTP)Phosphorylation. ATP is used.
CTP synthasecytidine 5'triphosphate(CTP)Glutamine and ATP are used.

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