Open questions in prebiotic chemistry to explain the origin of the four basic building blocks of life
One of the few biologists, Eugene Koonin
, Senior Investigator at the National Center for Biotechnology Information, a recognized expert in the field of evolutionary and computational biology, is honest enough to recognize that abiogenesis research has failed. He wrote in his book: The Logic of Chance page 351:
" Despite many interesting results to its credit, when judged by the straightforward criterion of reaching (or even approaching) the ultimate goal, the origin of life field is a failure
—we still do not have even a plausible coherent model, let alone a validated scenario, for the emergence of life on Earth. Certainly, this is due not to a lack of experimental and theoretical effort, but to the extraordinary intrinsic difficulty and complexity of the problem. A succession of exceedingly unlikely steps is essential for the origin of life, from the synthesis and accumulation of nucleotides to the origin of translation; through the multiplication of probabilities, these make the final outcome seem almost like a miracle.
Eliminative inductions argue for the truth of a proposition by demonstrating that competitors to that proposition are false. Either the origin of the basic building blocks of life and self-replicating cells are the result of the creative act by an intelligent designer, or the result of unguided random chemical reactions on the early earth. Science, rather than coming closer to demonstrate how life could have started, has not advanced and is further away to generating living cells starting with small molecules. Therefore, most likely, cells were created by an intelligent designer.
I have listed 27 open questions in regard to the origin of RNA and DNA on the early earth, 14 unsolved problems in regard to the origin of amino acids on the early earth, 12 in regard to phospholipid synthesis, and also unsolved problems in regard to carbohydrate production. The open problems are in reality far greater. This is just a small list. It is not just an issue of things that have not yet been figured out by abiogenesis research, but deep conceptual problems, like the fact that there were no natural selection mechanisms in place on the early earth. The implausibility of prevital RNA and DNA synthesis
RNA & DNA: It's prebiotic synthesis: Impossible !! Part 1
RNA & DNA: It's prebiotic synthesis: Impossible !! Part 2
How would prebiotic processes have purified the starting molecules to make RNA and DNA which were grossly impure? They would have been present in complex mixtures that contained a great variety of reactive molecules.
How did the Synthesis of the nitrogenic nucleobases in prebiotic environments occur?
How did fortuitous accidents select the five just-right nucleobases to make DNA and RNA, Two purines, and three pyrimidines?
How did unguided random events select purines with two rings, with nine atoms, forming the two rings: 5 carbon atoms and 4 nitrogen atoms, amongst almost unlimited possible configurations?
How did stochastic coincidence select pyrimidines with one ring, with six atoms, forming its ring: 4 carbon atoms and 2 nitrogen atoms, amongst an unfathomable number of possible configurations?
How did random trial and error foresee that this specific atomic arrangement of the nucleobases is required to get the right strength of the hydrogen bond to join the two DNA strands and form Watson–Crick base-pairing?
How did mechanisms without external direction foresee that this specific atomic arrangement would convey one of, if not the best possible genetic system to store information?
How would these functional bases have been separated from the confusing jumble of similar molecules that would also have been made?
How were high-energy precursors to produce purines and pyrimidines produced in a sufficiently concentrated form and joined to the assembly site?
How could the adenine-uracil interaction function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup" considering that its interaction is weak and nonspecific?
How could sufficient uracil nucleobases accumulate in prebiotic environments in sufficient quantities, if it has a half-life of only 12 years at 100◦C ?
How could the ribose 5 carbon sugar rings which form the RNA and DNA backbone have been selected, if 6 or 4 carbon rings, or even more or less, are equally possible but non-functional?
How would the functional ribose molecules have been separated from the non-functional sugars?
How were the correct nitrogen atom of the base and the correct carbon atom of the sugar selected to be joined together?
How could right-handed configurations of RNA and DNA have been selected in a racemic pool of right and left-handed molecules? Ribose must have been in its D form to adopt functional structures ( The homochirality problem )
How could random events have brought all the 3 parts together and bonded them in the right position ( probably over one million nucleotides would have been required ?)
How could prebiotic reactions have produced functional nucleosides? (There are no known ways of bringing about this thermodynamically uphill reaction in aqueous solution)
How could prebiotic glycosidic bond formation between nucleosides and the base have occurred if they are thermodynamically unstable in water, and overall intrinsically unstable?
How could RNA nucleotides have accumulated, if they degrade at warm temperatures in time periods ranging from nineteen days to twelve years? These are extremely short survival rates for the four RNA nucleotide building blocks.
How was phosphate, the third element, concentrated at reasonable concentrations?. (The concentrations in the oceans or lakes would have been very low)
How would prebiotic mechanisms phosphorylate the nucleosides at the correct site (the 5' position) if, in laboratory experiments, the 2' and 3' positions were also phosphorylated?
How could phosphate have been activated somehow? In order to promote the energy dispendious nucleotide polymerization reaction, and (energetically uphill) phosphorylation of the nucleoside had to be possible.
How was the energy supply accomplished to make RNA? In modern cells, energy is consumed to make RNA.
How could a transition from prebiotic to biochemical synthesis have occurred? There are a huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network.
How could RNA have formed, if it requires water to make them, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place?
How would the prebiotic synthesis transition of RNA to the highly regulated cellular metabolic synthesis have occurred? The pyrimidine synthesis pathway requires six regulated steps, seven enzymes, and energy in the form of ATP.
The starting material for purine biosynthesis is Ribose 5-phosphate, a product of the highly complex pentose phosphate pathway, which uses 12 enzymes. De novo purine synthesis pathway requires ten regulated steps, eleven enzymes, and energy in the form of ATP.
DNA is more stable than RNA. uracil (U) is replaced in DNA by thymine (T)
At the C2' position of ribose, an oxygen atom is removed by hypercomplex RNR molecular machines. The thymine-uracil exchange is the major chemical difference between DNA and RNA. Before being incorporated into the chromosomes, this essential modification takes place. The synthesis of thymine requires seven enzymes. De novo biosynthesis of thymine is an intricate and energetically expensive process.
All in all, not considering the metabolic pathways and enzymes required to make the precursors to start RNA and DNA synthesis, at least 26 enzymes are required. How did these enzymes emerge, if DNA is required to make them? Amino acids Chemical evolution of amino acids and proteins ? Impossible !!
How could ammonia (NH3), the precursor for amino acid synthesis, have accumulated on prebiotic earth, if the lifetime of ammonia would be short because of its photochemical dissociation?
How could prebiotic events have delivered organosulfur compounds required in a few amino acids used in life, if in nature sulfur exists only in its most oxidized form (sulfate or SO4), and only some unique groups of procaryotes mediate the reduction of SO4 to its most reduced state (sulfide or H2S)?
How did unguided stochastic coincidence select the right amongst over 500 that occur naturally on earth?
How was the concomitant synthesis of undesired or irrelevant by-products avoided?
How were bifunctional monomers, that is, molecules with two functional groups so they combine with two others selected, and unifunctional monomers (with only one functional group) sorted out?
How did prebiotic events produce the twenty amino acids used in life? Eight proteinogenic amino acids were never abiotically synthesized under prebiotic conditions.
How did a prebiotic synthesis of biological amino acids avoid the concomitant synthesis of undesired or irrelevant by-products?
How could achiral precursors of amino acids have produced and concentrated only left-handed amino acids? ( The homochirality problem )
How did the transition from prebiotic enantiomer selection to the enzymatic reaction of transamination occur that had to be extant when cellular self-replication and life began?
How would natural causes have selected twenty, and not more or less amino acids to make proteins?
How did natural events have foreknowledge that the selected amino acids are best suited to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets inside proteins?
How did nature "know" that the set of amino acids selected appears to be near ideal and optimal?
How did Amino acid synthesis regulation emerge? Biosynthetic pathways are often highly regulated such that building blocks are synthesized only when supplies are low.
How did the transition from prebiotic synthesis to cell synthesis of amino acids occur? A minimum of 112 enzymes is required to synthesize the 20 (+2) amino acids used in proteins. Prebiotic cell membrane synthesis
How could simple amphiphiles, which are molecules containing a nonpolar hydrophobic region and a polar hydrophilic region will self-assemble in aqueous solutions to form distinct structures such as micelles have been available in the prebiotic inventory if there has never been evidence for this? Furthermore, sources of compounds with hydrocarbon chains sufficiently long to form stable membranes are not known.
How could prebiotic mechanisms have transported and concentrated organic compounds to the pools and construction site?
How could membranous vesicles have self-assembled to form complex mixtures of organic compounds and ionic solutes, if science has no solution to this question?
How could there have been a prebiotic route of lipid compositions that could provide a membrane barrier sufficient to maintain proton gradients? Proton gradients are absolutely necessary for the generation of energy.
How to explain that lipid membranes would be useless without membrane proteins but how could membrane proteins have emerged or evolved in the absence of functional membranes?
How did prebiotic processes select hydrocarbon chains which must be in the range of 14 to 18 carbons in length? There was no physical necessity to form carbon chains of the right length nor hindrance to join chains of varying lengths. So they could have been existing of any size on the early earth.
How could there have been an "urge" for prebiotic compounds to add unsaturated cis double bonds near the center of the chain?
How is there a feasible route of prebiotic phospholipid synthesis, to the complex metabolic phospholipid and fatty acid synthesis pathways performed by multiple enzyme-catalyzed steps which had to be fully operational at LUCA?
How would random events start to attach two fatty acids to glycerol by ester or ether bonds rather than just one, necessary for the cell membrane stability?
How would random events start to produce biological membranes which are not composed of pure phospholipids, but instead are mixtures of several phospholipid species, often with a sterol admixture such as cholesterol? There is no feasible prebiotic mechanism to join the right mixtures.
How did unguided events produce the essential characteristic of living cells which is homeostasis, the ability to maintain a steady and more-or-less constant chemical balance in a changing environment? The first forms of life required an effective Ca2+ homeostatic system, which maintained intracellular Ca2+ at comfortably low concentrations—somewhere ∼10,000–20,000 times lower than that in the extracellular milieu. There was no mechanism to generate this gradient.
How was the transition generated from supposedly simple vesicles on the early earth to the ultracomplex membrane synthesis in modern cells, which would have to be extant in the last universal common ancestor, hosting at least over 70 enzymes? Prebiotic source of hydrocarbons
How would an ensemble of minerals present anywhere on the primitive Earth be capable of catalyzing each of the many steps of the reverse citric acid cycle? How would a cycle mysteriously organize itself topographically on a metal sulfide surface?
How would such a cycle, despite the lack of evidence of its existence, a transition to the “life-like” complexity of the Wood-Ljundahl cycle, or reverse TCA cycle, commonly proposed as the first carbon fixing cycles on earth? https://reasonandscience.catsboard.com/t1279p75-abiogenesis-is-mathematically-impossible#7759