A Guided Reading On Macromolecules With Review Questions: Fill & Download for Free

According to evolution, where did DNA come from?To answer the question , a bit of backward software engineering will be necessary.The first step is to confirm if it will be possible.According to the J Craig Venter Institute the possibility exist.“Genomic science has greatly enhanced our understanding of the biological world. It is enabling researchers to "read" the genetic code of organisms from all branches of life by sequencing the four letters that make up DNA. Sequencing genomes has now become routine, giving rise to thousands of genomes in the public databases. In essence, scientists are digitizing biology by converting the A, C, T, and G's of the chemical makeup of DNA into 1's and 0's in a computer. But can one reverse the process and start with 1's and 0's in a computer to define the characteristics of a living cell? We set out to answer this question. “and“Using the first synthetic cell, Mycoplasma mycoides JCVI-syn1.0 (built by this same team in 2010), JCVI-syn3.0 was developed through a design, build, and test (DBT) process using genes from JCVI-syn1.0. The new minimal synthetic cell contains only 531,000 base pairs and just 473 genes making it the smallest genome of any self-replicating organism.“and“Writing Biological CodeA biological cell is very much like a computer—the genome is the software that encodes the instructions of the cell and the cellular machinery is the hardware that interprets and runs the genome software. Major advances in DNA technologies have made it possible for biologists to now behave as software engineers and rewrite entire genomes to program new biological operating systems. “” The end resulted in a viable, self-replicating minimal synthetic cell that contained just 473 genes, 35 of which are RNA-coding. In addition, the cell contains a unique 16S gene sequence. ““The Institude was able to assign biological function to the majority of the genes with 41% of them responsible for genome expression information, 18% related to cell membrane structure and function, 17% related to cytosolic metabolism, and 7% preservation of genome information. However, a surprising 149 genes could not be assigned a specific biologichttp://jcvi.org/cms/research/projects/first-self-replicating-synthetic-bacterial-cell/overview/andhttp://www.jcvi.org/cms/research/projects/minimal-cell/overviewThe next step is to determine the stability of the code carrier. The longer the half life of the carrier the safer the code. DNA is not the code, it is only a code carrier, The sequence of adenine, guanine, cytosine and thymine forms the genetic code. The more unstable the code carrier molecule , the more the probability that this sequence will be changed, corrupting the code.The 2015 Nobel Chemistry Prize was rewarded to researchers who examined the stability of the DNA molecule.The Chemistry Nobel Prize 2015 was awarded toTomas Lindahl,Paul ModrichandAziz Sancar.The reasons the Royal Swedish Academy of Sciences gave for their decision :“The Nobel Prize in Chemistry 2015 is awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for having mapped, at a molecular level, how cells repair damaged DNA and safeguard the genetic information. Their work has provided fundamental knowledge of how a living cell functions and is, for instance, used for the development of new cancer treatments.Each day our DNA is damaged by UV radiation, free radicals and other carcinogenic substances, but even without such external attacks, a DNA molecule is inherently unstable. Thousands of spontaneous changes to a cell’s genome occur on a daily basis. Furthermore, defects can also arise when DNA is copied during cell division, a process that occurs several million times every day in the human body.The reason our genetic material does not disintegrate into complete chemical chaos is that a host of molecular systems continuously monitor and repair DNA. The Nobel Prize in Chemistry 2015 awards three pioneering scientists who have mapped how several of these repair systems function at a detailed molecular level.In the early 1970s, scientists believed that DNA was an extremely stable molecule, but Tomas Lindahl demonstrated that DNA decays at a rate that ought to have made the development of life on Earth impossible. This insight led him to discover a molecular machinery, base excision repair, which constantly counteracts the collapse of our DNA.”Quote from the press release announcing the Nobel Prize laureates in chemistry 2015https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2015/press.htmlTo determine of origin of our present DNA , the next step is to determinate the minimum requirements to obtain a stable DNA molecule.Research done by Stanley Miller ( Miller -Urey fame) , Lindahl and the J Craig Venter Institute will be useful to determine the minimum requirements. There are many review and research papers available regarding their work but the following will be suffice;1Rates of decompensation of ribose and other sugars :Implications for chemical evolution Procedings.Nationall Academy of Sciences USA 92 91995) – Rosa Larralde , P Robertson and Stanley Miller2Instability and decay of the primary structure of DNA -Tomas Lindahl – Nature vol 363)3 Review The Origin and Early Evolution of Life: Prebiotic Chemistry, the Pre-RNA World, and Time Antonio Lazcano Stanley L MillerCell vol 85http://www.cell.com/cell/issue?pii=S0092-8674(00)X0108-04. http://www.jcvi.org/cms/research/projects/minimal-cell/overview/http://science.sciencemag.org/content/351/6280/aad6253.ful​ljkey=77AGRUAdvXIP2&keytype=ref&siteid=scihttp://www.jcvi.org/cms/press/press-releases/full-text/article/first-minimal-synthetic-bacterial-cell-designed-and-constructed-by-scientists-at-venter-institute-an/Quotes from these papers“A minimal cell is usually defined as a cell in which all genes are essential. This definition is incomplete, because the genetic requirements for survival, and therefore the minimal genome size, depend on the environment in which the cell is grown. The work described here has been conducted in medium that supplies virtually all the small molecules required for life. A minimal genome determined under such permissive conditions should reveal a core set of environment-independent functions that are necessary and sufficient for life. Under less permissive conditions, we expect that additional genes will be required.”\ quote from 4)\“. The team also explored gene order and how that affects cell growth and viability, noting that gene content was more critical to cell viability than gene order. “ / qute from 4 /“All macromolecules ( including sugars ) are inherentunstable” / quote from 2)/“Changing ribose to deoxyribose in an important step in the synthesis of DNA “ /quote from 2 / (enzyme called ribonucleotide reductase is necessary without which DNA will not be synthetized)“A“although deoxyribose increase the stability of the code carriers , the base sugar bonds of ribonucleosides are much less susceptible to hydrolysis than those of deoxyribonuclesides” -. causing a weak spot in DNA's stability “ !( quote from 2 )“Added to these problems is the fact that any prebiotic synthesis of ribose or nucleosides would give a racemic mixture, and all template polymerization experiments so far show enantiomeric cross inhibition. “ /quote from 3 /“All the evidence reviewed here suggests that stability of monomers and polymers essential for the origin of life strongly limited the possibility of a slow emergence of life “ / quote from 3/“The instability problem could be overcome if the ribose nucleosides could have formed early, because nucleosides are quite stable owing to the absence of free aldehyde in its sugar. However, there is no efficient prebiotic synthesis of purine ribosides and no prebiotic synthesis of pyrimidine nucleosides at all. Added to these problems is the fact that any prebiotic synthesis of ribose or nucleosides would give a racemic mixture, and all template polymerization experiments so far show enantiomeric cross inhibition. “/ quote from 3/The JCVI-syn3.0 indicates the bare minimum coding memory necessary necessary for a cell to survive., The JCVI -syn-3 was created and survive in optimal laboratory conditions. In the harsh conditions of the old earth's natural environment i , more genes ( genetic memory) were probably required. At least a DNA molecule with 561,530 base is required to maintain cellular life.The next step is to investigate the possibility and efficiency of genetic code execution outside a living cell..Code carriers occur in the following forms outside living cellsViruses ( DNA and RNA viruses)ViroidsNaked DNANaked RNAThere is no indications that extra cellular nucleic acids are active or replicating , outside living cells. The only known exceptions to this rule occur in well controlled strict artificial conditions, in laboratories.There are still no experimental evidence to counteract both Miller's and Lindahl's comments regarding the limitations and instability of a RNA world. All the present support for a RNA world depends on circumstantial evidence . There is still ongoing research in an effort to discover alternative pathways. (PNA, TNA etc)The answer to the question about the origin of DNA , is it origin is slil a mystery.DNA is is a highly complex molecule, and could not have arranged itself spontaneously.Possible ancestors of DNA: nucleic acids under investigation are PNA( thioester peptide nucleic acid) p-RNA ( pyranosylRNA) , and TNA (threose nucleic acid)None of these possible ancestors of the genetic code are natural occurring molecules found in our present world. They are synthetic creations that are investigated as possible links between non living molecules and the living chemistry occurring in cells. The living chemistry is guided by the genetic code that resides on the DNA and partly on the RNA molecules.The origin of the genetic code, of DNA and of RNA are still hidden in mysteries.If the code and early life developed on pRNA,TNA etc,, than shouldn't pRNA , TNA or whatever, have foreknowledge. Foreknowledge of what?. Foreknowledge of DNA’s instability, of DNA ‘s capability of being an excellent code carrier of it contained proofreading protection and with foreknowledge evolve the protective mechanisms. Life would have been impossible without the code protection!All readers are advised to read the review article by Lazcano and Millerhttp://www.cell.com/cell/issue?pii=S0092-8674(00)X0108-A major problem , one mentioned in the comments about the question is vary valid and still not answered. “ The NDT [neo-Darwinian theory] is supposed to explain how the information of life has been built up by evolution.”. The NDT has a basic flaw , noise (mutations) can not their wildest dreams increase information. Ordinarily mutations are nothing but noise. Gene duplication , gene exchange etc is more likely candidates to explain the increasing formation contained on the DNA molecule.The basic unanswered question remains, did the the code proceed life with a build in ( pre-programmed ) ability to evolve .(the worst nightmare if you are an atheist).

Why l. -Amino acids in nature? Should add : why d- sugars and l -amino acids in nature? To answer the question we must differentiate between two periods in earth’s history .An prebiotic period and an biotic period. There is a difference in the synthesis of life's major major building blocks ( pentose sugars, amino acids and purine and pyrimidines ) as it occurred on the e prebiotic earth and as it is occurring on the present biotic earth.In the biotic world the building blocks are produced by enzymatic catalyzation of chemicals . These reactions , with the exception of a few rare instances, produce d- sugars and l-amino acids.The pentose sugars form part of the backbone of RNA and DNA molecules. and multiple amino acids combine to form polypeptides . ( very long chains of polypeptides are called proteins)The prebiotic synthesis, however produced mixtures of the the d- and l-configurations of sugars and amino acids as confirmed by experiments conducted by Stanley Miller during the early 1950 s .http://science.sciencemag.org/content/117/3046/528/Science Vol 117 Issue 3046 page 528 April 25, 1953(Harold Urey was the Head of the Department in the Faculty were the experiments were conducted and Urey’s name is attached to the experiment due to protocol. )In the years since Miller's work, many variants of his procedures have been tried. Virtually all the small molecules that are associated with life have been formed:17 of the 20 amino acids used in protein synthesis,All the purines and pyrimidines used in nucleic acid synthesis.But the abiotic synthesis of ribose and therefore of nucleotides , proved to be more difficult.Miller realized that it wasn't going to be plain sailing to turn his discovery into life.The following two articles ( Miller co-author) will help to illustrate the difficulties, difficulties that still exist and that are at the center of many ongoing research projects.www.pnas.org/content/92/18/8158.full.pdfRates of decomposition of ribose and other sugars –PNASMay 30, 1995 - (RNA world/pre-RNA world/ribose stability).ROSA LARRALDE*, MICHAEL P. RBERTSONt, AND STANLEY L. MILLER (1995)andhttp://www.cell.com/cell/abstract/S0092-8674(00)81263-5?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867400812635%3Fshowall%3Dtrue(follow link and click full text) ( or copy and paste link in address bar if you experience problems) Remember to clicl FULL TEXTThe Origin and Early Evolution of Life: Prebiotic Chemistry, the Pre-RNA World, and TimeCell Volume 85, Issue 6, p793–798, 14 June 1996Antonio Lazcano Stanley L Miller (1996)Careful reading of these two papers will reveal the following problems: racemic mixtures and enantiomeric cross inhibition, the instability of macromolecules, the problem of possible depletion of nutrients ( building blocks) and the difficulty to really determine the necessary environment for life’s beginnings. These articles also indicate that the discovery of the importance of d- and l- enantiomers originated a quarter of century ago and we are still struggling to find an answer why life is driven by l-amino acids and d- nucleotides.The following four papers either review or present research efforts to answer the question about the homochirality (l-amino acids , d- sugars and d- nucleotides ) of life systems.(selected from a very large data basis of papers (review and research) about the topic of homochirality associated with life(i)The Origin of Biological HomochiralityCold Spring Harb Perspect Biol. 2010 May; 2(5): a002147.doi: 10.1101/cshperspect.a002147The Origin of Biological HomochiralityDonna G. Blackmond(ii)Autocatalytic replication and homochirality in biopolymers: is homochirality a requirement of life or a result of it?Send toAstrobiology.2012 Sep;12(9):818-29. doi: 10.1089/ast.2012.0819. Epub 2012 Aug 29.Autocatalytic replication and homochirality in biopolymers: is homochirality a requirement of life or a result of it?Wu M1, Walker SI, Higgs PG.(Unfortunately no open source aricle availabe ( Must either be a subscriber to Nature or buy the article of you want to read full text )(iii)A Cross-chiral RNA Polymerase Ribozyme:Nature. 2014 Nov 20; 515(7527): 440–442.Published online 2014 Oct 29. doi: 10.1038/nature13900A Cross-chiral RNA Polymerase RibozymeJonathan T. Sczepanski and Gerald F. Joyce(iv)http://www.nature.com/nchem/journal/v6/n7/abs/nchem.1981.htmlChiral encoding may provide a simple solution to the origin of lifeAshley Brewer & Anthony P. DavisNature Chemistry 6, 569–574 (2014)(Unfortunately no open source aricle availabe ( Must either be a subscriber to Nature or buy the article of you want to read full text )These four papers were selected to show the diversity of opinions regarding the homochirality of living chemistry .We are still waiting for a Miller (and a Pasteur) type experimental setup to get an answer (experiments that only use chemicals that were available on the prebiotic earth without sophisticated laboratory interventions and the continuous guidence by highly intelligent humans).Sczepanski and Joyce gave arguably the best answer to the question about chirality but there is a drawback.Check the list of their methods and of the materials they used. They used chemicals that are very unlikely to have been present in the prebiotic world.The genetic code may also play a major role in the homochirality of life and studying its origin may be helpful.Refer to the following two papers:(i)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293468/Origin and evolution of the genetic code: the universal enigmaIUBMB Life. 2009 Feb; 61(2): 99–111.Eugene V. Koonin* and Artem S. NovozhilovANDhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072225Structural Phylogenomics Retrodicts the Origin of the Genetic Code and Uncovers the Evolutionary Impact of Protein FlexibilityGustavo Caetano-Anollés , Minglei Wang,Derek Caetano-AnollésPLOS Journals Published: August 21, 2013Careful reading of all the papers referred to, will indicate the importance of the chirality factor. The prebiotic synthesized building blocks are racemic mixtures. . Miller’s and similar experiments confirmed that that racemic or near racemic mixture are the result of the prebiotic chemical reactions. Enantiomeric cross inhibition in such mixtures is a major blocking stone that prevent the synthesis of macromolecules.Chiral selecting “ machines” selecting only one type enantiomere or “machines “ able to change one enatiomere into another. ( all possibilities mentioned in the referrals).The concentration of the building blocks ( nutrients) on the prebiotic earth depended on the rate at which they were synthesized . Thus raises a concern that a few authors mentioned ( in the referred articles) namely, the possibility of depletion. If l-amino acids ,d-sugars are incorporated into new molecules ( l-polypeptides and d- nucleotides) at a rate that exceeded their production rate ,the levels of available l- amino acids and d-sugars would decrease . If this happened their concentrations might drop below the threshold necessary to continue to supply enough of the preferred enantiomers. The result : cessation of construction of l-polypeptides and d-nucleotides. . The same apply to the dipeptide synthesis postulated by Gustavo Caetano-Anollés et al.Any of the suggestions and the postulations in the referred articles might work, but what is the probability in a prebiotic word.Our present knowledge about the minimum requirements for cellular life is also clouding our understanding of the minimum environmental conditions necessary for life to exist. . ( continuous purposeful chemical reactions = life).Is JCVI-syn 3.0 ( minimal synthetic cell) the simplest cell , with a minimum possible DNA size, the only possible factory capable of producing homochiral building blocks.?http://www.jcvi.org/cms/research/projects/minimal-cell/overview/http://science.sciencemag.org/content/351/6280/aad625(UNFORTUNATELY NO OPEN SOURCE TEXT)Compare this also this the press release of the Swedish Royal Academy , announcing the 2015 Chemistry NobelPrize laureates .The Nobel Prize in Chemistry 2015The answer to the question at hand is currently still based on views without concrete answers. Very similar to period residing in the Northern Hemisphere’s Winter of 1859, beautifully summarized herelink:http://www.thesilvertablet.net/WINTERWINTER%201859.pdfThe problem of how racemic mixtures of dead building blocks become living chemical reactions that evolve to evolve let . Doritt to comment : “Pasteur, of course, was right, but with one major exception. If we think of contemporary organisms in the present, life begets life, and like begets like. But if we look into the past, we quickly realize that there must have been at least one time when Pasteur’s dictum did not hold. Some 3.8 to 4 billion years ago, life on Earth emerged from nonlife.”The Genetic code ProblemHow did the come come aboutKoonin and Novozhilov concluded “ Summarizing the state of the art in the study of the code evolution, we cannot escape considerable skepticism. It seems that the two-pronged fundamental question: “why is the genetic code the way it is and how did it come to be?”, that was asked over 50 years ago, at the dawn of molecular biology, might remain pertinent even in another 50 years. Our consolation is that we cannot think of a more fundamental problem in biology.”https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293468/Add to this another co-existing fundamental biological problem, the mystery of homochirality of life.More on the genetic code’s origin:Genetic code: Lucky chance or fundamental law of nature. Victor A Gusev, Dirk Schulze-MakuchPhysic of Life Reviews ( (2004 )202-22920-%20Lucky%20chance%20or%20fundamental%20law%20of%20nature.pdfThe only difference between living matter and non living matter is the multiple continuous chemical reactions occurring in living cells. Chemical reactions guided by the genetic code through ribozymes and enzymes. These ,,zymes catalysis chemical reactions that without the enzymic catalysts would occur at a very slow snai’s pace , incompatible with life. The enzymatic catalysts speed up the reactions to rates measured in milliseconds.The answer to the question at hand, is still a mystery . Is it only a scientific mystery or is theology and philosophy also involved in solving the mystery, ( Natural sciences can only answer the HOW and the other two disciplines the WHY problem) ..Which of the three disciplines has the answer? Currently is is up to the beholder to speculate. The eye of the beholder is the worldview of the beholder.p s( Interestingly Doritt predicted the JCVI -syn 1-0 the precursor of JCVI-syn 3.0).)

To answer the question I will defer to well known researchers using quotes from their research and review papers.1. DNA is not a code, it is a code carrier. The sequence of the bases determine the genetic code.The researchers at the J Caig Venter Institute describe it as follows:“Genomic science has greatly enhanced our understanding of the biological world. It is enabling researchers to "read" the genetic code of organisms from all branches of life by sequencing the four letters that make up DNA. Sequencing genomes has now become routine, giving rise to thousands of genomes in the public databases. In essence, scientists are digitizing biology by converting the A, C, T, and G's of the chemical makeup of DNA into 1's and 0's in a computer. But can one reverse the process and start with 1's and 0's in a computer to define the characteristics of a living cell? We set out to answer this question. “http://jcvi.org/cms/research/projects/first-self-replicating-synthetic-bacterial-cell/overview/RNA also a code carrier.2. How stable are the known biological code carriers ?The Chemistry Nobel Prize 2015 was awarded toTomas LindahlPaul ModrichandAziz Sancar.The reasons the Royal Swedish Academy of Sciences gave for their decision :“The Nobel Prize in Chemistry 2015 is awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for having mapped, at a molecular level, how cells repair damaged DNA and safeguard the genetic information. Their work has provided fundamental knowledge of how a living cell functions and is, for instance, used for the development of new cancer treatments.Each day our DNA is damaged by UV radiation, free radicals and other carcinogenic substances, but even without such external attacks, a DNA molecule is inherently unstable. Thousands of spontaneous changes to a cell’s genome occur on a daily basis. Furthermore, defects can also arise when DNA is copied during cell division, a process that occurs several million times every day in the human body.The reason our genetic material does not disintegrate into complete chemical chaos is that a host of molecular systems continuously monitor and repair DNA. The Nobel Prize in Chemistry 2015 awards three pioneering scientists who have mapped how several of these repair systems function at a detailed molecular level.In the early 1970s, scientists believed that DNA was an extremely stable molecule, but Tomas Lindahl demonstrated that DNA decays at a rate that ought to have made the development of life on Earth impossible. This insight led him to discover a molecular machinery, base excision repair, which constantly counteracts the collapse of our DNA.Aziz Sancar has mapped nucleotide excision repair, the mechanism that cells use to repair UV damage to DNA. The cell also utilises nucleotide excision repair to correct defects caused by mutagenic substances, among other things.”3. All biological macro-molecules spontaneously decompose.Lets look at the stability of the building blocksRibose . Stanley Miller ( Miller -Urey fame) made the following observation :“The existence of the RNA world, in which RNA acted as a catalyst as well as an informational macromolecule, assumes a large prebiotic source of ribose or the existence of pre-RNA molecules with backbones different from ribose-phosphate. The generally accepted prebiotic synthesis of ribose, the formose reaction, yields numerous sugars without any selectivity. Even if there were a selective synthesis of ribose, there is still the problem of stability. Sugars are known to be unstable in strong acid or base, but there are few data for neutral solutions. Therefore, we have measured the rate of decomposition of ribose between pH 4 and pH 8 from 40°C to 120°C. The ribose half-lives are very short (73 min at pH 7.0 and 100°C and 44 years at pH 7.0 and 0°C). The other aldopentoses and aldohexoses have half-lives within an order of magnitude of these values, as do 2-deoxyribose, ribose 5-phosphate, and ribose 2,4-bisphosphate. These results suggest that the backbone of the first genetic material could not have contained ribose or other sugars because of their instability.The above results show that stability considerations preclude the use of ribose and other sugars as prebiotic reagents except under very special conditions. It follows that ribose and other sugars were not components of the first genetic material and that other possibilities, such as the peptide nucleic acids (36) and other non-sugar-based backbones, should be examined. “(Rates of decompensation of ribose and other sugars :Implications for chemical evolutionProcedings. National Academy of Sciences USA 92 91995) – Rosa Larralde , P Robertson ans Stanley Miller)Lindahl agrees with this view and the effect of ribose on RNA's stabilty:“All macro-molecules are inherently unstableNucleic acids also undergo spontaneous decomposition in solution. RNA being particularly vulnerable. The 2'- hydroxyl group of ribose cause the phosphodiester bonds of RNA molecules to be very susceptible to hydrolysis. “Changing ribose to deoxyribose in an important step in the synthesis of DNADeoxyribose is generated from ribose 5-phosphate by enzymes called ribonucleotide reductases. These enzymes catalyze the deoxygenation process.Lindahl discovered that although deoxyribose greatly increases the stability , it caused a chemical price.“Base sugar bonds of ribonucleosides are much less susceptible to hydrolysis than those ofdeoxyribonuclesides. '“In metabolically active cells, DNA would be expected to undergo depurination ( with accompanying loss of genetic information) at a rate similar to that of DNA in a solution'“Fortunately endonucleases ( repair enzymes) rapidly initiate a DNA repair process.(Instability and decay of the primary structure of DNA -Tomas Lindahl – Nature vol 363)4. The minimum requirements for cellular life to exists.Back to the J Craig Venter Institute (JCVI)JVCI-syn3.0 release notes“Using the first synthetic cell, Mycoplasma mycoides JCVI-syn1.0 (built by this same team in 2010), JCVI-syn3.0 was developed through a design, build, and test (DBT) process using genes from JCVI-syn1.0. The new minimal synthetic cell contains only 531,000 base pairs and just 473 genes making it the smallest genome of any self-replicating organism.““A biological cell is very much like a computer—the genome is the software that encodes the instructions of the cell and the cellular machinery is the hardware that interprets and runs the genome software. Major advances in DNA technologies have made it possible for biologists to now behave as software engineers and rewrite entire genomes to program new biological operating systems. ““The end resulted in a viable, self-replicating minimal synthetic cell that contained just 473 genes, 35 of which are RNA-coding. In addition, the cell contains a unique 16S gene sequence. “The Institute was able to assign biological function to the majority of the genes with 41% of them responsible for genome expression information, 18% related to cell membrane structure and function, 17% related to cytosolic metabolism, and 7% preservation of genome information. However, a surprising 149 genes could not be assigned a specific biological function despite intensive study. This remains an area of continued work for the researchers. “(JCVI press leases)Life is the sum of all the chemical reactions taking place in an organism. When the reactions seize, life seizes. Most of these reactions will proceed at a very slow rate in the absence of enzymes. Each group of enzymes is very specific and will catalyze only specific reactions. Enzymes are proteins coded for by the genetic code residing on the DNA molecule.The ability of a cell to move, replicate, and recast itself according to the needs of the organism which it serves, comes at a price. (continuous chemical activity ). The extreme flexibility of cells takes its origin from the constant turnover of nearly every component with which they are made. To achieve this ,the cell needs DNA the control and guide the process. The price to be able to replace, to replicate , to recast and to produce more chemicals depends on the availability DNA.5. Probabilities of macro-molecules surviving outside living cell.Already mentioned that none of the macro-molecules seem stable enough to be able to evolve into more complex forms and at the same time be able to maintain genetic memory , if they reside outside a living cell. Viruses , Vidroids, naked RNA , DNA etc. can be regarded as inactive , non-living entities when they are encountered extra cellularly. . The are unable to duplicate or to control chemical reactions outside a living cell.Macromolecular code carriers are not stable enough to execute sustainable code directive manipulation to their surroundings outside a living cell . A living cell's machinery are also necessary to protect against code deterioration. This instability is applicable to all organic macro-molecules, sugars and proteins included.“A common theme seen in all of the sample types (forensic, archaeological and archival) is that in order for RNA to be preserved, there needs to be some form of barrier or macromolecular structure between the environment and the nucleic acids. “(Fordyce, S.L., Kampmann, ML., van Doorn, N.L. et al. Investig Genet (2013) 4: 7. doi:10.1186/2041-2223-4-7 )RNA and DNA are only alive when they actively partake in a cell's life giving machinery. They can only evolve when part of these machinery.The binary code of a computer is only executed when is powered ( manipulation of electro-magnetic fields). A cell is only powered when the correct chemical reactions ( also depending on electron movement and also a type of electro-magnetic field manipulation) occur. ( The correct electro -magnetic manipulation under the direction of the genetic code only occurs in living cells).This instability of the nucleic acids is one of the reasons Francis Cric proposed an extra terrestrial source of life on earth. (panspermia). . ( supported by Leslie Orgel)The question was “Is the involvement of intelligence necessary for the evolution of organisms?”Was the complex life cellular machinery and the further evolvement of these machinery the result of guidance by a superior intelligence?The answer is in the eye of the beholder. It depends on how the beholder explain a code that reside on a code carrier. A carrier which existence is depended on the code it is carrying. Without the genetic code, no code carrier.The arguments that the code developed spontaneously on precursors , has one drawback, all the possible known precursors are probably not stable enough to accumulate enough memory to spontaneously devise a code able to control even a simple prokaryotic cell. Biochemistry depends on the presence of enzymes that act as catalysts. Without the enzymatic catalysts most biologic reactions will proceed at a very slow rate. Without sustainable memory storage,enzymes will disappear.Yes we know that natural occurring RNA producing catalysts exist in nature and that RNA itself, especially rRNA can catalyze its own duplication , but it is a weak and slow catalyst when compared to the enzymes coded by the genetic code. RNA intrinsic instability also remains a drawback. RNA is probably also not stable enough to store the information of ' how to make enzymes', long enough in its memory, to sustain evolving life.The RNA world postulation rest on speculative circumstantial evidence, also proposed by Miller , Lindahl and others but it is presently still just speculation.The beholder must decide what is possible and what is impossible in the “mysterious” quantum world. Is multi-verses a possibility.? Is a super intelligence residing in a quantum world a possibility ?.These are the questions the beholder should answer.The instability of macro-molecules is also a phenomena caused by the laws of chemistry, due to the proclivity of electrons to tend to occupy the lowest stable energy levels in atoms and molecules.