Intermolecular Enzymatic Encoding of Nucleic Acid, Steroid Complexes: A New Theory on the Chemical Origin of Life Based on Evidence of Structural Symmetry
IIntermolecular Enzymatic Encoding of Nucleic Acid, SteroidComplexes: A New Theory on the Chemical Origin of LifeBased on Evidence of Structural Symmetry
Charles D. Schaper, [email protected] City, California, USAJuly 5, 2020
Abstract
The origin of life is one of the greatest mysteries. The mechanism for the synthesisof DNA is synonymous with the chemical origin of life, and theories have been devel-oped along many lines of reasoning, but resolving all requirements remains a challenge,such as defining an objective path to produce sequences of encoded nucleotides pairedas adenine to thymine and guanine to cytosine. Here, a new theory for the origin ofDNA is presented. The theory is based upon three lines of experimental evidence andagreement of structural symmetry between DNA nucleotides and steroid hormones, andintroduces a new concept of synthesizing both structural and functional characteristicsof DNA at the same time within a single unified complex of interleaved tetra-ringedstructures, steroid molecules which form reaction vessels that serve as co-enzymaticbuilding blocks. The new theory indicates that the establishment of the DNA nu-cleotide code is among the very first synthesis steps. Moreover, as a consequence ofthe intermolecular synthesis of both structural and functional characteristics withina unified complex, there is a culminating process step that sets forth in motion bothDNA and the steroid structures that subsequently trigger replication and transcrip-tion, as well as protein translation, thereby resulting in the instantaneous release oflife function. a r X i v : . [ q - b i o . O T ] J u l raphical Abstract A schematic of the methodology to produce encoded proteins starting from the basic building blocksof the two steroid molecules. A complex is formed in which the blocks are configured and arrangedto establish enzymatic environments to induce amination reactions to co-synthesize within a unifiedcomplex DNA nucleotides and steroid molecules that ultimately, upon release, control transcriptionaland translational function. To complete the complex, the reaction vessels are wired together alongthe edges through phosphodiester covalent attachment. During this encoding process, an event inline with the second law of thermodynamics enables the separation of the encoded DNA structureinto a double helix, and an associated set of steroid molecules that enable function. The steroidmolecule may then bind onto the DNA strands, which will cause its separation. The new access willenable the encoded steroid structure to act as an intermediary and induce protein manufacturingthrough assembly of amino acids in a nucleotide triplet format organized through binding with thecorresponding steroid molecules. Introduction
The origin of life is inherent to central tenets of science and philosophy; thus, as it remainsone of the greatest unsolved mysteries, many prospective theories have been developed andstudied at great length [1, 2, 3]. To focus this broad topic, as all cellular organisms of lifecontain DNA, the origin of life is synonymous with revealing the mechanisms responsiblefor synthesizing DNA starting from basic materials and processes that would have comeinto existence about the time Earth was formed, over four billion years ago [4, 5]. In termsof the creation of the first DNA molecule, there are excellent articles written on the rangeof ideas, such as those that revolve around starting with RNA molecules and others thatare based upon geological events [6, 7, 8, 9]. Thus, in putting forth a new theory on theorigin of DNA, as this article develops, it would be distractive to compare the new ideasdirectly with all of the alternative theories, because of the wide range, and varying levelsof evidentiary basis [10, 14]. Therefore, in this introductory section, the objective is tocharacterize the constituents of a valid theory that reveals the synthesis of life function.For each requirement, the results of this article are highlighted that characterize a newtheory on the origin of DNA.
In developing a theory for the origin of life, a difficult problem to address immediately isthe so-called “chicken and egg dilemma”, as to which one came first [11]. For example,in the case of the transcription process under current theories, DNA is required to formproteins, but proteins are needed by DNA to initiate transcription. Thus, there has beenthe speculation that DNA came about from an “RNA world”, and this theory has takenthe preeminent position in explaining the origin of life [12]. Thus, this approach wouldgenerate DNA from building blocks, but it would be unclear as to the driving force behindthis self-assemble process of significant complexity. In the theory presented in this researcharticle, it is shown that the answer to the question of which one came first, the chickenor the egg, the answer is both: that is, the DNA molecule and the steroid molecules thattrigger replication and transcription were developed in an intermolecular linked manner atthe same time in tandem with the steroid molecule affecting the DNA molecule and viceversa, both starting from the same molecule type, paired together and co-synthesized in aunified enzymatic complex.A valid theory on the origin of DNA should also provide answers to basic questionson its molecular structure. For example, the following questions should be answered:why are purine and pyrimidine the bases that comprise DNA? How are the arc distancesbetween pairs of nucleotides determined? Why does adenine-thymine only have two internalhydrogen bonds, whereas cytosine-guanine have three internal hydrogen bonds? How is thesynthesis of DNA related to the formation of the double helix? What is the structural basisfor DNA nucleotides? Many theories on the origin of life never even get to this level of detail3o provide a reasonable response to these basic questions, and most suggest that it is thisway, because it has to be this way. In this article, however, a process sequence is developedthat within its first few steps provides quantitative reasoning to such structural questionson DNA, as well as its initial prebiotic functional application of protein translation.Another important requirement in the development of a theory on the origin of DNA isthat the materials and processes utilized in forming DNA should be feasible during the timewhen Earth was formed. Some have considered DNA to have been possibly constructedup to 4 billion years ago, which is close to the estimates on the time at which Earth wasformed [13]. To accommodate for further pushbacks, the theories should even considerDNA to be generated essentially at the same time as the formation of the earth. Thus,lengthy evolutionary processes, or theories based upon chance of multiple sequential eventsthat have low yields, would be hard to satisfy this category. The materials and processesshould be developed that are consistent with these conditions, and the processes shouldbe relatively rapid, and preferably simple. Most theories on the origin of DNA are validin applying chemicals and processes that would have been present at the time when Earthwas formed, but have challenges in terms of its simplicity. However, as shown here, thematerials in the proposed theory and process steps are consistent with these conditions,and the processes are of an elementary nature defined at the onset of the synthesis.Ideally, the new theory on the origin of DNA should not only explain the past, butoffer a path going forward. Approaches which utilize actions by chance or require lengthydevelopment periods are less interesting than those that can be used in synthesis applica-tions or to discover new medical knowledge. DNA is central to the operation, and a betterunderstanding of it should result in new medicines, new therapies, and new approaches.Random events are thus not satisfying in the development of a theory for the creation oflife function through DNA, and are not helpful in addressing basic human inquiries on theorigins of life. In this article, it is shown that DNA is the result from the synthesis of alogical set of steps, which can lead not only to a better understanding of DNA, but also toproduce new ideas such as in the transcription process itself.One great challenge in the development of a theory on the origin of DNA is in testingtheory, which may imply the capability to recreate it. That is a daunting challenge as forsome theories it is not possible to develop a protocol to test the hypothesis, especially thosethat rely on slow periods of evolution, random events, or exogenous processes. However, if itwere possible to have a “chemical fossil” of DNA, which has underlying characteristic of thestructure of DNA, then it would be possible to have a first line of comparative analysis.In this article the identification of a discovery of a chemical fossil of DNA is identifiedfor the first time, in which it is indicated that the molecular structure of the steroidmolecule is embedded into each and every DNA nucleotide to the present day. Thus, thetheory developed in this article is matched to this discovery, thereby providing a verifiablemetric of its validity, which the alternative theories do not address. Moreover, it is furthershown through analysis of measurable efficacy of certain pharmaceuticals, that the resultsare consistent with the structural arrangements involved in the molecules comprising the4trategy of synthesizing DNA and steroid molecules by a basic set of processes, and henceprovide a biomarker as evidence of the developed theory.Most importantly and generally the largest stumbling block is that the new theoryhas to resolve the origins of the “code of life”. Literature acknowledges that this is thebiggest problem for the current theories [15, 16]. There is no clear-cut answer, or evenanything close in explaining the code of life as AGTC, including those that start withinthe RNA world. Thus, while the theories describe how the molecules can be formed, theydo not characterize the organizational strategy associated with the capability of DNA tostore and retrieve information. In the second step of the proposed process flow, it is shownhow the code of life is generated and its functional nature established. Furthermore, themethodology enables the mapping of the base 3 nucleotide triplet to amino acid via thesteroid molecule, described in the book [37]. Combined with the alignment of the resultswith experimental evidence including those consistent with the fundamental molecularstructure of DNA, these are significant reasons to support the validity of the developedtheory on the origin of DNA. It is the only one that can explain the communication channeland orgin of information content, along with the structure and function requirements forlife [37].Finally, a new theory on the origin of DNA should have a novelty, that is an insightthat brings something new to the table. In this research article, the concept of synthesizingthe paired mechanisms of the structure and function of DNA simultaneously in a unifiedcomplex, in which structure and function are effectively designed as one. Thus, when theco-formative processes are complete, DNA and its associated steroid molecules are putinto practice immediately to establish in an instant a central life function of replicationand protein translation through a transcription procedure. Therefore, the equivalent of abig bang moment for life function is enabled, of which there is paired synthesis of DNA andsteroid molecules, developed in tandem as a co-synthesized intermolecular unified complex,dependent upon each other in one sequence of steps, co-optimized in structure and function,released simultaneously.Furthermore, since the purpose of DNA is to translate to proteins, a valid theory onits origin needs to describe the mechanism by which the complementary base pairs map toamino acids. Again, almost all alternative theories do not address this issue as they do noteven have the capability to determine how the base pair code is defined in the first place,and thus leave this important component unattended. However, in the theory describedin this article, this mapping of DNA base pair to amino acid is achieved for constructs,and importantly, indicate that it is a natural outcome of the procedure of associating theintegrated, paired synthesis also permits encoding of an intermediary to achieve the aminoacid to base mapping, which is fully described in my recent book that follows from thiswork [37].Although there are challenges in developing a theory on the creation of DNA, it ispossible to develop a checklist for the requirements associated with an explanation on theorigin of life. In so doing, exciting explanations of the past are possible, unraveling many5ysteries, and a path going forward is developed for exciting new discoveries. Therefore,as this theory that will be described herein satisfies this checklist of basic requirements, itshould enable this theory as a leading candidate among all theories describing the synthesisof the structure and function of DNA, its molecular triggers, that is specialized moleculesof a steroid construct, for protein production, and hence enable a chemical origin of life.
As this new theory will be disruptive and is quite distinct to the well published approachassociated with the RNA world among other approaches, it can have appearances of “fringescience”, at least according [17]. If this may be the case, it is recommended that in order tointroduce the new theory, a comparison back to the original concepts is warranted, in whichthe current mainstream approach can be compared against the proposed new approach.Thus, in addition to the checklist of Section 1, an apples-to-apples comparison can be madeas to analyzing the take-off point of current approach versus the new point, pertaining tothe question: what new insight is there that requires a new way of thinking, in this caseabout origin of DNA.In this regard, an introductory paragraph of [5], while brief, is informative. Referencingthe book by Monod [18], it is noted that molecular biologists, in the years hitherto thediscovery of DNA structure to the modern approach to study of its origin, consideredlife function to coincide with the synthesis of the first DNA molecule. Moreover, theynoted that Watson and Crick speculated of a quality of DNA which permitted proteingeneration without the need for proteins, quoting: “whether a special enzyme would berequired to carry out the polymerization or whether the existing single helical chain couldact effectively as an enzyme” [19]. Further, [5] note that this thinking was in line withSchrodinger’s prediction of an aperiodic crystal as characteristic of life function [20]. Theresearch community however did not take this direction, however and opted for the currentlinear logic of independently synthesized molecules of RNA leading up to DNA.
In this research article, the new theory and developments are aligned with the speculationof Watson and Crick, Schrodinger’s aperiodic crystal, and the original molecular biologists,who favored DNA as the origin of life; but adds a new concept to enable reality for thisline of thinking: Here, I aim to prove that the original DNA molecule was but half of aco-enzymatic, co-synthesized, co-encoded “master” complex, in which the other half wascomprised of ultimately its triggering elements, that is steroid molecules, which enabledlife function persuant to DNA when both were simultaneously released in a decompositionof the master complex. The details will follow on how this fits together, and althoughit may seem complicated, is actually simple and is pursuant to Occam’s Razor, in thatas soon as the master complex is synthesized, and separated, life function is created, and6he evolutionary processes can begin, that is, the originating work is done with sufficientconcentration of the released molecules to permit further development immediately. More-over, this approach will satisfy among others, one important conundrum that has puzzledtheoreticians: the second law of thermodynamics related to the ordered nature of DNA. Inthat DNA is derived, along with its triggering elements, it is the disordering of the mastercomplex into two ordered complexes that explains the satisfaction of the second law, or thetendency to induce disorder from order, where DNA becomes the product of a disorderingevent, as will be seen, to lower the overall energy of the composite system.The new results are described in my new book [37], whose contents are outlined inAppendix D. The results include the communication channels of information theoreticstarting from encoding of the unified complex, transmission in the form of a double helixand steroid molecules, and then access of the double helix by the steroid molecules, so asto produce a chain of amino acids forming a protein molecule.
To develop the new theory, experimental data is first described in support of it, therebyindicating a discovery that I had made in [21, 22] that there is a common structure, thesteroid molecule, embedded in each in every DNA nucleotide pair, which will serve as abeacon to develop the new theory on the origin of DNA. In addition, it is shown thatthis can be extended to match steroid hormones structural to DNA, and even indicatefunctionality as a present-day pharmacological biomarker associated with a process that canbe correlated with the structure of DNA. After presentation of the experimental evidence,which serves as the basis for the theoretical developments, the process steps are describedto synthesize not only encoded DNA, but also encoded steroid molecules. These units areco-developed at the same time within the same unified complex, and when released canbe put into practice immediately. For prebiotic conditions, it can serve as the basis togenerate the protein structures that can later take over in function as known today, suchas the enzymes involved in transcription and translation. The appendix describes reactionmechanisms to support the process steps indicated in this section.
Three levels of experimental evidence are indicated to support the theoretical developments.The first experimental evidence is that of a chemical fossil of DNA in which there is a basismolecule, that is a structural basis, embedded within each nucleotide pairing of DNA,which consists of a four ringed steroid molecule. The second experimental evidence is amolecular fossil associated with DNA as the alignment of steroid hormones to the DNAnucleotide pairs, which is important in the paired development of both molecules withinthe same complex. The third experimental evidence is pharmacological information as a7iomarker of DNA indicating the importance of the paired coupling of DNA nucleotidesand steroid molecules.
To develop an experimental basis to validate the theory, a structural analysis of DNAnucleotide base pairings is analyzed. In Figure 1(a), the front of the DNA nucleotidesis indicated for each of the four pairings as listed from top to bottom in the figure asAdenine-Thymine (A-T), Cytosine-Guanine (C-G), Thymine-Adenine (T-A), and Guanine-Cytosine (G-C). In Figure 1(b), the backside of each of the four DNA nucleotide pairingsis illustrated. This is obtained by flipping the front orientation in a horizontal direction,and both sides are important to the analysis. Also included in the illustrations are thephosphodiester backbone and the sugar molecules. The arrangements are envisioned asthe DNA nucleotide structure printed on paper, and viewing it from the front and theback side. Also included in the illustration is the hydrogen bonding of the base pairings,in which it is shown that there are three hydrogen bonds for the C-G and G-C pairs, andtwo internal hydrogen bonds for the A-T and T-A pairs. It is of importance that at thecarbon two position of thymine, there exists a functional oxygen element, but there is nocorresponding element on adenine that could provide a hydrogen bond as a link.To indicate that the four fused ring structure of a steroid is a “chemical fossil of DNA”,the extraordinary result is presented in the four red overlays each of Figure 1(a) and (b).This overlay is obtained by connecting precisely a total of seventeen oxygen, nitrogen, andcarbon elements of the base pairs in a particular manner to produce a tetra-ring structureembedded within each of the four DNA nucleotide pairs. This can be achieved for eachbase pair, front and back, and the match is in perfect correspondence when comparingeach of the matches. The four-ring structure is exactly in the shape of a steroid molecule,which was originally identified in the preprints [21, 22]. The orientation of the moleculeis in perfect correspondence when analyzing the frontside for the A-T and G-C pairings,where a purine molecule starts the association on the 5’ side, while on the backside thealignment is perfect for the T-A and C-G pairings when the pyrimidine molecule startsthe 5’ pair. There is a stretching along one of the rings where the purine and pyrimidinecome into alignment through hydrogen bonding. Thus, this association is a chemical fossilof DNA of which theories on the origin of DNA must identify. The theory developed inthis research article begins from the steroid molecule, and thus is in perfect harmony withthe basis defined by this chemical fossil of DNA.
The second line of support involves the symmetry of the steroid hormone with the DNAnucleotide pairs with respect to the intermolecular binding. Namely the corticosteroids,which have a mid-molecule group, should bind onto thymine. This result is consistent8 a) Front (b) Back
Figure 1: (a) In a structural analysis of the four possible DNA nucleotide pairs presented fromtop to bottom as Adenine-Thymine (A-T), Cytosine-Guanine (C-G), Thymine-Adenine(T-A), and Guanine-Cytosine (G-C), there is a common structure in the shape of a fourring steroid molecule at each of the nucleotides.; (b) Examining the “back” side of thenormal presentation, which is equivalent to that which would be seen on the back of aprinted page with the molecule on the front, the common structure of the steroid moleculeis obtained for each of the nucleotide pairs. The coupling of back side to front side isachieved by flipping the common structure, thus indicative that one common structure isappropriate for each of the pairs as the backside orientation becomes reoriented properlyon the frontside, and vice versa. with the hydrogen bond that was presented very early into the development, essentiallythe definition of the DNA nucleotide code itself. It should be the case that the symmetryof the steroid molecule is capable of forming an intermolecular hydrogen bond with A-Tand T-A, and not needed for C-G and G-C, the result is evaluated with the representationof DNA and the steroid hormones. As shown in Figures 2(a) and 2(b), this symmetry isindicated and shown. Of course, having developed the symmetry relations between steroidhormones and DNA nucleotides as described in the preprint [22], this mapping was anobjective. Thus, it is apparent that this representation is still conserved to this date, whichincludes the relationship with steroid hormones, the orientation, the intermolecular bonds,the connection to the phosphodiester backbone, and even the configuration of the endgroups. Moreover, together, the orientation and class of steroid hormone correspondenceform a new code for DNA as shown in Figure 2(c), which is further described in the preprint[23]. Moreover, this is consistent with the indication in Section 2.2 which noted that thenucleotide pairs with pyrimidines along left (5’) side had to be flipped in order to achievetheir proper orientation consistent with the double helix. Hence it is logical that the9teroid representation would involve a forward side and a reverse side of orientation. Thisconfiguration of forward and reverse orientation is thus apparently still conserved to thisdate in the DNA molecule. Thus, the second line of experimental evidence of a structuralbiology nature to identify a “molecular fossil” of DNA, which is the structural match of thesteroid hormone, is in support of the new theory on the origin of life is successful of whichsteroid molecules and DNA nucleotides are synthesized together within the same unifiedcomplex. (a) Front with Steroid Hormone (b) Back with Steroid Hormone (c) New Code for DNA Nucleotides
Figure 2: Consistent with the result of a common steroid molecule embedded in the DNA nu-cleotides, the intermolecular bonding capability is examined with respect to thymine.Classes of steroid molecules are defined with cortisol defining those molecules which havea mid-molecule functional group, and testosterone representing those that do not havea mid-molecule functional group. The objective is to overlay the steroid such that threehydrogen bonds are formed. on the common steroid structure for each of the four possiblesteroid structures, a class of steroid hormones are assigned with the objective of achievinga total of three hydrogen bonds when overlaid with the steroid hormone. In (a), the cortisolsteroid hormone forms an intermolecular bond with the (A-T) pairing, and thus a total ofthree hydrogen bonds result. In the case for (G-C), there is already three internal hydrogenbonds, and thus testosterone is used as the overlay since it does not have a mid-moleculehydroxyl group. For cortisol and testosterone, the end groups are available for connec-tion with the phosphodiester backbone, which was shown in the simulation. (b) Followingthe same protocol, cortisol forms an intermolecular hydrogen bond with the (T-A) pair,while testosterone couples with the (C-G) nucleotide pair, but on the back-side. This isconsistent with the need to rotate the pyrimidine molecules at the 5’ strand to achieve thedouble helix when ejecting the steroid triggering molecules. (c) The location of the steroidstructure is indicated as, F for front and B for back, and the corresponding class of struc-turally compatible steroid class, H indicates the class of cortisol-like molecules, which hasa functional group positioned to interact with the available functional group of thymine,and S signifies the class of testosterone-like molecules, which do not have a functionalgroup positioned that can interact with the available functional group of thymine. .1.3 Pharmacological efficacy of steroid hormones as a biomarker of DNA functionality To further validate the method, experimental data is evaluated that can be used to provethe claim of this theory that the intermolecular bond which essentially established theDNA code is critical, and thus serves as a biomarker of DNA to guide in the develop-ment of a theory of its origin. In this experimental analysis, the intermolecular hydrogenbond is examined of coupling steroid hormones similar to cortisol to thymine for corticos-teroid data. The handbooks indicate that the relative activity of the steroids dexametha-sone:prednisolone:cortisol is approximately 25:4:1 and that prednisone, in its native form,is inactive as it must be converted into prednisolone in the liver before it can be used [24].This relationship is consistent with the intermolecular bond to thymine by its steroid trig-gering molecule as presented in this study. In Figure 3(a), the relationship of prednisoloneto thymine is indicated, in which it is shown that it is possible to form an intermolecularhydrogen bond with thymine. However, in Figure 3(b), the relationship of prednisone tothymine is indicated, in which it is not possible to form an intermolecular hydrogen bond.Note that the OH group is the only difference between prednisolone and prednisone. Thisprecise result is consistent with the efficacy of prednisone, which experimentally shows noactivity, and must be converted into prednisolone before becoming active.Further experimental data is consistent with the theory. In Figure 3(c), the relationshipbetween the steroid hormone cortisol and thymine is indicated, which can form an inter-molecular hydrogen bond. With respect to prednisolone, the only difference is an extradouble bond in the ring of prednisolone within thymine. The additional double bond willaid in stabilizing the intermolecular hydrogen bond of thymine and prednisolone, and mayalso provide favorable structural arrangement in terms of the angle. Further, by exami-nation of dexamethasone in Figure 3(d), the activity will be even further enhanced, dueto the fluoride group stabilizing the intermolecular hydrogen bond even more than pred-nisolone, thereby increasing its relative activity. Thus, the third line of evidence based onexperimental data is consistent with the paired development of the steroid molecule andDNA nucleotides.
To derive the integration of structure and function within one unified complex, the devel-opments begin from the work described in these [21, 22], which indicated the structuralsymmetry of steroid molecules, steroid hormones and DNA nucleotides. Thus, to continuethe developments, these molecules will be stacked and hence hydrogen bonding will stabi-lize the structure, as indicated in Figure 14. This particular format is described later inthe research article, Section A.7, on how the diketone group, hydroxyl group, and five car-bon element ring are formed from a starting material. In stacking these steroid molecules,intermolecular hydrogen bonding is deployed to secure the structure as indicated in Figure14, noting that the rings are aligned, with the five carbon ring situated in alignment with11 a) Prednisolone (b) Prednisone(c) Cortisol (d) Dexamethasone
Figure 3: For analysis of experimental results, the efficacy of steroid therapeutics is examined.(a) The capability to form an intermolecular hydrogen bond between prednisolone andthymine. (b) It is not possible to form an intermolecular hydrogen bond between pred-nisone and thymine. Indeed prednisone is inactive in practice, and must be convertedto prednisolone in order for it to be potent. This result provides evidence in proving theclaims of this manuscript. (c) The overlay of the nominal steroid hormone cortisol isshown capability to form an intermolecular hydrogen bond with thymine. With respectto prednisolone, the double bond in the ring adjacent to thymine aid in enhancing theintermolecular hydrogen bond strength, and thus increased potency is expected for pred-nisolone relative to cortisol, which is indeed the case in practice. (d) Dexamethasone alsois capable of forming an intermolecular hydrogen bond with thymine. In addition, the flu-oride group and double bond will aid in the potency, and thus it would be expected to havegreater potency than prednisolone, and cortisol, which again aligns with that observed inpractice the six carbon ring. It is noted that these paired molecules are enantiomers, mirror imagesof each other.
As noted in reference [5], in the original work of Watson and Crick speculated that thedouble helix of nucleic acids may have an enzymatic nature; but that idea did not takehold and since then the research direction has trended toward the linear logic of a synthesisstarting from single-strand RNA nucleotides, which would ultimately lead to the DNAdouble helix complex. However, based upon the analysis presented in this research article, it12 igure 4: The developments focus on a paired structure of two molecules comprised of four fusedrings, in the shape of a steroid molecule, with three six carbon aromatic rings, and onefive carbon aromatic ring, that is functionalized at each end, one by a hydroxyl group andthe other by ketones. Hydrogen bonding secures the two molecules. The generation of thisarrangement is discussed later in the article. is possible to re-evaluate the speculation of Watson and Crick within an analytic frameworkof the origination of DNA as an enzymatic construct of interleaved tetra-ringed structures,of which one section is covalently bonded to a phosphodiester backbone, while the adjacentstructure is connected through hydrogen bonding in close proximity.As indicated in Figure 17, the coordination of the paired building blocks enables asequence of effective reaction vessels, secured at the ends through phosphodiester covalentcoupling. This confined environment enables the potential for an enzymatic capability inwhich the temporary formation of bonding arrangements to permit intermolecular cyclicstructures that can establish element substitution, the degradation of chemical bonds toreduce intramolecular stress, and the differentiation of the templates into their individualcapacity as a nucleotide base. While the structures did have aromatic stabilization, theintermolecular structures may also have benefitted from resonance stabilization, and thusthe intermolecular constraints to maintain an in-plane structure during the synthesis stepswould have promoted the present-day configuration in which the original aromatic structurewas traded for an amine based self-assembled construct of a planar configuration. Relevantreaction sequences to this synthesis route are the stereoselective Diels-Alder reactions [25,26, 27], for this type of integrated structure.
Now, the key to explain the encoding of DNA nucleotides is shown. In stacking the nextpair of steroid molecules on top of the initiating pair of steroid molecules, the orientationwill define ultimately the “letters” of the nucleotide pair, whether it is adenine-thymine,thymine-adenine, guanine-cytosine, or cytosine-guanine! There are exactly four configura-tions, when placing the second set on top of the first set, and as will be seen later, onemolecule of the pair will define the nucleotide pair, and the other will define the coopera-tive steroid molecule that will interact with DNA to trigger replication and transcription.13 igure 5: By interleaving the tetra-ringed aromatic structures, and securing each alternating pairto a phosphodiester backbone, there exists the capacity for an enzymatic function in thedevelopment of each molecule. It is proposed that this constitutes a series of reactionvessels, which together with aggresive environmental conditions, the co-synthesis of theDNA nucleotides, and its triggering elements, comprised as steroid molecules, would haveresulted from interactive co-development. There are two styles of enzymatic reactionvessels. The directly coupled are used in the synthesis of the coupling to the phosphodiesterbase, and the vessel that is defined by the meeting of two paired units, is used in thedifferentiation and separation of the DNA nucleotides and the steroid molecules.
For example, in Figure 6(a), the third molecule starting from the bottom will take onthe DNA nucleotide pairing of adenine-thymine, after the process steps to be describedare completed. By flipping the upper pair of molecules, that is molecules 3 and 4, as aunit vertically, the thymine-adenine base pairing will result as molecule 3 as indicated inFigure6(b). Rotating the upper pair of molecules as a unit one hundred eighty degreeswill result in the guanine-cytosine base pair as molecule 3 as indicated in Figure 6(c), andflipping the upper pair of molecules as a unit will result in cytosine-guanine as molecule 3as in Figure 6(d). It is noted that the determination of the nucleotide pair of molecule 3is depending upon the starting orientation of molecule 1, and thus any adjacent letter canbe obtained independent of the starting point of molecule 1.
Remarkably, that is all that is really necessary to create a coded DNA molecule as wellas its steroid molecules, which will trigger genetic replication and transcription, that isthe results of Figure 6.
It is possible to create any set of letters from AGCT, as wellas its steroid triggering components, by using the strategy of pairing and orientation,which is an amazingly simple process, as it needs to be! Moreover, in addition to thebase 4 code associated with the orientation of the pairings, another code is defined. Thesteroid triggers have two orientations relative to the upper pair of molecules, meaning thatthere is alignment in terms of hydrogen bonding to either one side or another. Thus,in addition to encoding what will become the nucleotide pair, it also encodes the typeof steroid molecule, as affiliated with its hydrogen bonding location. To further examinethe orientation of the base-pairing, Figure 7 indicates that there are four configurations,and only four configurations in planar relation to the underlying molecule, which willbecome its paired steroid. It is also noted that in addition to coding the DNA nucleotides,14 a) A-T motif(b) T-A motif (c) G-C motif (d) C-G motif
Figure 6: As a major result for this research article, the code of DNA is formed by stacking twocoupled, functionalized steroid molecules, in which here the DNA nucleotide code is definedfor the first and third molecules, starting from the bottom. In the representation, theconfiguration is shown for the third molecule, numbering started from the bottom, whichafter going through the steps described in this article will result in the following nucleotidepairs: (a) adenine-thymine (A-T). (b) thymine-adenine (T-A). (c) guanine-cytosine (G-C). (d) cytosine-guanine (C-G). In addition to the four types of base pairings of the DNAmolecule, the paired steroid molecule will also be encoded into two types. it also encodes the steroid molecules. As will be developed, the steroid molecules arecoordinated with amino acids during the translation process, and thus will provide thespecificity required for protein translation, as well as an inherent capability to inducestrand separation.To continue the discussion, it is interesting to use an example, such as the nucleotiderepresentation of TAGTC. In Figure 8(a), the stack of ten molecules for the creation ofthe five nucleotide pair of (T-A), (A-T), (G-C), (T-A), (C-G), starting from the bottom,15 a) To become A-T (b) To become T-A(c) To become G-C (d) To become C-G(e) Referencing Paired Molecule to be En-coded Steroid
Figure 7: The orientation of the adjacent molecule of the second pair with respect to the moleculeof the first pair will define the final result. There are four orientations possible. In theexample of Figure 6, the different orientations are shown. As will be shown, the couplingelements between the adjacent molecules will be used to define the base pairing. Note thatthere are four rings that define each structure, and that there are four and only four basepairings. These molecules after paired synthesis with steroid structures will become (a)A-T, (b) T-A, (c) G-C, and (d) C-G. (e) In addition, the paired steroid molecule willenable replication and transcription, which is the referencing molecule co-synthesized withthe DNA nucleotides. If rings 2 and 3 are aligned it will become a steroid interactive with(A-T) and (T-A); if not aligned, a steroid consistent with (G-C) and (C-G). is presented. The other five molecules will be associated with steroid molecules, which canbe used for replication and transcription. Both will be developed in the same complex, andboth are interactive and influence each other. The nucleotides will be formed on molecules1, 3, 5, 7 and 9, and the steroids will be formed on molecules 2, 4, 6, and 8, with thenumbering starting from the bottom. There is another molecule below molecule 1 thatinfluences its configuration, and would ultimately result in a steroid, but that molecule ispaired, and in order to keep it brief, only the transformation on molecule 1 will be shown,and not the corresponding change to its paired molecule, which would be situated below it.Further, the starting orientation of molecule 1 is taken to indicate the independence of theletter sequencing. The top molecule 10 only couples to molecule 9, and does not influenceits configuration. 16 a) Example Rings as TAGTC (b) van der Waals spheres
Figure 8: (a) To use an example in describing the work, the structure is used which will result inthe nucleotide pairs of (T-A), (A-T), (G-C), (T-A), (C-G) for molecules 1, 3, 5, 7, 9,numbering from the bottom. It will also include four steroids configured as corticosteroidssimilar to cortisol, for molecules 2 and 6, and similar to testosterone from molecules 4and 8. The tenth molecule would interact with the eleventh molecule. (b) The van derWaals spheres indicate hydrogen bonding along two edges, and hydrogen bonding staggeredon either side of the structure.
Having produced the paired and encoded structures of both DNA and steroid molecules,the bases will only be accessible for replication and transcription if the strands are pos-sible to separate. Fortunately, the steroid molecule is available, and can bind onto thephosphodiester chain to enable strand separation. This occurs through stabilization of thestrands, which are vibrating and oscillating molecular constructs. Thus there is kinetic en-ergy transferred to potential energy through the stabilization process, which is an overallenergy function whose internal energy must be dissipated through for example moleculardisorganization, and bond breaking in this case. An alternative would be an increase in17emperature of the molecule, hence vibratory modes, but this may also induce strand sepa-ration. Approximate mathematical representation for the process is indicated in Equations1 and 2, for the energy dissipation, E s ( x ) about the binding site, and the strand separationfrom its nominal position, S ( x ). The equations characterizing the strand separation aregiven by: E s ( x ) = 12 (1 + tanh( k x x )) (1) S ( x ) = k b (1 − (tanh( k x x ) )) + S n (2)where the parameters are associated with hydrogen bond energy k x = 1/40, coupling k b =3,and nominal separation S n =1.8 ˚A, and x runs from 0 to 200 nucleotides, with the resultthan mirrored from -200 to 0 nucleotides about the binding point. These equations can beused to approximate the strand opening away from the binding site. It is dependent uponthe energy associated with the hydrogen bonding keeping the strands intact, as when theterm tanh( k x x ) approaches unity, the strand separation will be equal to its nominal value.Other formulations for strand separation can use wave equations to describe the motion ofthe DNA strands, which will be constrained by the cross-coupling of the steroid molecule,and thus result in reflected wave patterns that will induce interference patterns, and bondseparation for bubble formation.As the DNA molecule is stabilized by binding with the steroid molecule, there must bea balance in energy in terms of a release through bond breaking to be nearly equivalentto that of the stabilization provided by the binding event. Essentially, the DNA strandsact as two strings in constant motion, which is fluidic, and with the cross-bonding inducedby the steroid molecule, that is the triggering element, it acts as a pinch-point, and thestrands, which were in relatively independent motion become constrained at one point, andaround that point, a small bubble must form through hydrogen bond breaking upstreamand downstream of the pinch-point. In Figure 9(a) the binding of the steroid moleculeonto the formed DNA complex is indicated in a molecular model as to its feasibility. InFigure 9(b) the electrostatic potential is indicated of the steroid molecule to show that thenegative potential of the phosphodiester zone will enable alignment of the steroid moleculefor binding. In Figure 9(c), the profile of the strand separation is approximated on eitherside of the binding site. It is possible to deploy multiple steroid molecules to induce astronger association and knoting of the DNA strands, and thereby improve the durationof the subsequent opening of the strands of the nucleic acid. With this chemical procedure, the prebiotic production of encoded proteins originatingfrom nucleic acids can be precisely defined, both in its initiation as a prebiotic functionand transition to the present-day methodology, whereas, other than the present method,18 a) van der Waals spheres (b) Electrostatic Po-tential (c) Strand Separation
Figure 9: (a) The binding of the steroid molecule onto the formed DNA complex to induce strandseparation. (b) The electrostatic potential of the binding site, which is achieved throughhydrogen bonding at both ends, attaching to the phosphodiester coupling. (c) The for-mation of the transcription bubble on either side of the binding point up to two hundrednucleotides. The quality of the binding point will determine the width of the transcribingseparation of strands. alternative theories on the origin of life have very little if anything to say about the method-ology of protein translation. The steroid molecule is a key component, as it enables theguidance of the DNA molecule, thereby encoding both itself and the DNA structure, andalso effectively results in encoded amino acids, which can be mapped to the DNA sequencethrough the intermediary steroid molecule. See [37] for more information on translationusing the steroid molecule in combination with DNA to develop an interaction vessel ofthe base 3 sequence. Moreover, the steroid molecule enables the strand separation of theDNA molecule to provide access to the nucleotide sequence.An overview of the mechanistic flow is indicated in Figure 10 to produce encodedproteins starting from basic tetra-ringed structures that are configured in a stacked formatas in Figure 14. Through a fabrication process, associating nucleotide pairing in conjunctionwith its paired steroid molecule, the phosphodiester connection is constructed along bothedges of the structure. At a certain point, the model becomes rigid, and the drive to thelower energy double helix induces a rotation of the formed nucleotides, ejecting the steroidand reducing the unified complex to just the double helix, which is more stable, but ofmuch lower information content than the original unified complex.It is noted that the unified complex prior to its separation into a double helix andsteroid molecules, would be a natural site for the accumulation of amino acids along theedge of the complex and down the center. There is significant charge along the edgesthat would attract the carboxyl and amine groupings, and the spacing is appropriate as19ell, averaging roughly seven angstroms, which is consistent with the steroid to nucleotidespacing. Thus, there would be significant building of the concentration of the amino acidsurrounding the unified complex such that when separation occurs, assembly into aminoacid chains can proceed immediately.After the separation event occurs, the DNA is in a double helix format, but is accessiblefor transcription through the binding of the encoded steroid molecule onto the encodednucleotide. As indicated in Section 2.3, the binding will open the strands for binding of theencoded steroid molecules onto half of the complementary base. There is an association ofthe amino acids to steroid molecules which is defined by the steroid molecules in conjunctionwith the double helix effectively defining a interaction vessel based upon size and chemicalstructure of the amino acid [37]. This process induces the formation of encoded proteins asthe fluidity of the steroidal attachment to the half base will enable the presentation of theamino acids within the interaction vessel, resulting ultimately in the chain propagation ofthe formation of the peptide bond.
Figure 10: A schematic of the methodology to produce encoded proteins starting from the basicbuilding blocks of the two steroid molecules. A complex is formed in which the blocksare configured and then wired together along the edges through the phosphodiester cova-lent attachment and through the center through stabilization provided bysteroid hydrogenbinding. During this encoding process, a separation event enables the separation ofthe encoded DNA structure into a double helix, and the steroid complex. The steroidmolecule may then bind onto the DNA strands, which will cause its separation. The newaccess will be addressed by the encoded steroid structure to induce protein manufactur-ing through binding of amino acids. After release of the protein, a new protein may bedeveloped until the binding site of the steroid onto the DNA strands is disassociated.
The structural association of the amino acid to the steroid molecule shows very precisematching. The full set of 20 amino acid matches seems to be possible to assign the structural20elation of the steroid structure, as it is a base four structure, to the amino acid structureto mirror that of the present-day code, although here the association is performed directlyon the double helix. As shown in Figure 11, it is possible to assign a structure for each ofthe amino acids. As indicated in my book [37], the match is based on the structural andchemical characteristics of the amino acid.
Figure 11: The translation table for the orientation of the steroid molecules. The translationtable and the processes of forming the interaction vessel for the first DNA moleculesis presented further in my recent book [37].
When there is separation of the unified complex, the double helix will form, whichrequires a rotation of some of the nucleotides and an ejection of the steroid molecules andamino acids, connected through hydrogen bonding. The availability of the DNA and thesteroid molecules will come into association, and the strands will separate because of thestabilization force provided by the steroid molecule, which will focus the vibrational andoscillatory nodes of the strands to points surrounding the binding point. The result isa separation of strands, and the binding of the steroid molecule onto the complementarybases of the nucleotides. This will allow for the binding of the amino acids onto the steroidstructure, and the result is an encoded protein structure, which can be replicated. Thedouble helix can also be repliated and error corrected using this procedure [37].
In addition to providing the mechanisms for generating proteins from amino acids, thesteroid molecule, as an intermediary, has to have an ability to participate in a feedback21oop to promote those amino acid sequences which are more likely to be of use in thesurrounding environment, and thus induce increases in the availability of the molecule tofurther participate in molecular interactions. In Figure 12, the feedback loop is presented,in which the steroid molecule binding onto the strands induces strand separation, therebyaccommodating transcription of amino acids into proteins. If the proteins are utilized, itwill exit the strand, and made the steroid structures available for further binding. Thisfeedback will continue onto the molecular structures inducing separation as well, as theforces from repeated implementation of the amino acid groupings on the strands maycause the degradation of the steroid strand separation element, and thereby terminatethe strand separation and transcription. Therefore, proteins that feedback to maintain orinhibit strand separation will also have an impact on the transcription rates.
Figure 12: The feedback loop to increase the rate of protein generation for those proteins that aremore successful, that is find greater usage. In this block diagram, the steroid moleculeconcentration triggers the strand separation, which is also a function of the enhancerand inhibitor concentration which may influence the trigger zone. The protein moleculewill also influence the steroid trigger, as a higher degree of use will place more force onthe trigger point, and thus may disturb transcription. In the figure, S ( t ) denotes steroidstructures capable of inducing transcription, A ( t ) denotes amino acid concentration overtime, and P ( t ) denotes proteins that are synthesized and leave the DNA molecule forusage in the surrounding environment. As mediated through the steroid molecule, which functions for prebiotic applications toinitiate transcription and as an intermediary for translation to enable protein generation, itsregulation becomes a point at which cellular and later systems integration can take place.Control of the concentration and transportation of steroid molecules into the cytoplasmand nucleus thus is able to differentiate the cellular objective, and therefore is itself abuilding block for further development ultimately resultant in systems performance. Thetransition to tRNA from steroid molecules would provide a more structured environmentfor protein generation through separation of function.
As a valid theory describing the origin of DNA needs to be able to provide detailed answersto questions on its structure, the approach developed in this research article provides suchanswers both with regard to DNA nucleotides as well as steroid hormones, and even the22evelopment of proteins comprised of amino acids. For example, questions that can beaddressed are those that pertain to the most basic of which as to how the base four codeis fundamentally defined, extending to the most detailed, such as a quantifiable metricassociated with the arc distance between nucleotide pairs, which correlates with the pitchof the stacked basis molecules, both approximately seven angstroms. Moreover, thereis agreement on the structural configuration, such as the rotation required to orient thenucleotides in correspondence to the present-day the double helix, which thereby enables adriving force to release the co-synthesized steroid molecules. In addition, there is agreementin the combination of a ketone and a hydroxyl group to the phosphor element, which wasneeded in order to enable hydrogen bonding with both ends of the steroid molecules, as thegroup is typically expressed as PO − . Remarkably and simply, there were four orientationsof one pair of steroid molecules to a second pair of orientations, thereby defining a base 4code to DNA when formed as a sequential stack. There is a match in the structural biologyof the steroid molecule, steroid hormones, and paired nucleotide molecules: It has beenshown that the match is perfect and undeniable, formed by a trace of precisely seventeencarbon, oxygen and nitrogen elements of nucleotide pairs. And from this structural match,the mechanisms for the origin of DNA nucleotides and its related type of steroid moleculeshas been derived.Early in the process, the “code of life” is defined, whereas alternative theories on theorigin of life struggle with this concept, and here it is immediately defined. This is a keystep and insight, in which there is co-synthesis intermolecular development of the targetand trigger. Moreover, the parallel development of the DNA as target and the steroidmolecule, and their simultaneous release and tied development, including the rotation ofthe nucleotides with the formation of the double helix as a driving force, constitutes a“big bang” moment in the creation of life function. As it resolves the “chicken and egg”problem as to which one came first, whereby the answer is both and it was always tiedsince both were developed in an optimal intermolecular manner, is a satisfying answer. Byhaving the form of the trigger and target derive from the same structure, and intertwinein the simultaneous development, an optimized structure with respect to both molecularconfigurations is achieved.In developing this research, a striking result is the simplicity of the materials and inparticular the process mechanisms involved in establishing the code of DNA nucleotidesequences. Considering that DNA developed soon after the formation of Earth accordingto present estimates, it had to be this way, that is simplistic and robust. There is not theneed for a lengthy evolutionary process requiring multiple building blocks to synthesize andput into practice, as the materials and functionality of DNA are correlated. A confluence ofunrelated probabilistic events is not required to generate molecular structures for lifeforms,or a sequential period of development of critical components: the development of thefundamental form of molecular life structure and function is achievable in a parallel yetlinear fashion. Moreover, the development of the steroid molecules at the same time as theDNA nucleotides also accelerates and simplifies the development of a critical life function.23o produce the coded structure and alternative outcomes, the methodology indicated inthis article, in which two cyclic structures are paired, and then paired again, can be utilizedto form other structures that can contain encoded larger molecules as well as their molecularfunction enablers. This would be applicable to the formation of molecular storage devices,and the approach described in the article can be used to create alternative structuresby manipulating the orientation of the molecules, and number of rings. Furthermore, theapproach described in this paper can synthesize at the same time both the storage medium,as well as the access mechanism through the parallel development of the steroid triggeringmolecule. It is possible for precise replication of certain portions of the molecule throughthe use of the steroid triggering molecule, that is equivalent to transcription.This methodology also should enable a questioning on how gene transcription maybe performed. The new approach to transcription involves the direct connection with thesteroid molecule to bind onto the DNA nucleotide, as it is pre-programmed since both weredeveloped in parallel, and one influenced the other through intermolecular binding throughco-structural development. Current strategy for transcription is through a receptor, henceindirect, but these results indicate that the steroid molecule is integrated with the DNAmolecule, and is thus capable of inducing replication and transcription without the need fora receptor. These ideas that steroids and the DNA nucleotides share the same structure,and thus there is likelihood that the binding of the steroid hormone to DNA nucleotidestriggers gene transcription as first proposed and developed in the preprint [21], and theseresults on the origin of DNA should solidify those ideas. The driving force for transcriptionis the stabilization energy provided by the steroid molecule that can be dissipated throughdestabilization about the bound area via lengthening of nearby hydrogen bonds along thenucleic acid strands. Thus, if the current methodology of protein induced transcription iscorrect, then there was a early life mechanism of transcription that did not require proteins,but rather utilized steroidal molecules.The results indicate that the reason for purine and pyrimidine as the bases that compriseDNA as follows: Purine and pyrimidine together account for three of the four rings of thesteroid molecule, and the coordination through hydrogen bonds accounts for the fourth ring.Yet another mystery that is further resolved by this work is the location of the missinghydrogen bond of the adenine-thymine pair relative to the cytosine-guanine pair. WhileA-T has two internal hydrogen bonds, there is an available oxygen element on thyminethat can form an intermolecular hydrogen bond with the mid-molecule hydroxyl group ofcorticosteroids, such as the steroid hormone cortisol. Both results are further describedin the preprints [21, 22]. This result, which is verified experimentally since prednisolonepossesses activity whereas prednisone has no activity prior to conversion to prednisolone,provides hard evidence that the symmetry between steroid hormones and DNA nucleotidesis more than coincidental, but is in fact functional. This result is important, as previouslythe A-T pairs were considered as “weak”, but the complex can be made strong whencoupled with an intermolecular hydrogen bond from corticosteroids.A major advantage of this approach is that the translation of proteins from amino24cids is immediately defined and consistent with the overall framework. Thus, the entiresequence of replication, transcription and translation is apparent, which is far further thanalternative theories on the origins of DNA. The areas where additional development wouldinclude some of the details associated with the specificity of the amino acid to the functionalsites of the steroid molecule.The steroid molecule apparently is an inherent structure of DNA, as it is difficult toargue against that there is an embedded structure traced into each and every nucleotidepair comprising nucleic acids. Thus, these results have defined the structural basis of DNAas the steroid molecule. There are a variety of similar structures within that family ofmolecules that can be used as the trigger for DNA to enable transcription. Thus, steroidmolecules should undergo close examination for health benefits than they currently are.Corticosteroids are a first line of defense in inflammatory diseases, but other forms ofsteroids, including hormone replacement therapies, and other forms of synthetic steroidhormones should be closely studied, as currently there seems to be a barrier attached tothese molecules. Life function is inherently derived from the steroid molecule, and thus itsuse for therapeutic purposes should be closely assessed.The structural symmetry of steroid hormones and DNA nucleotides is a practical result,for example in the area of design of therapeutics. It was indicated that each functionalelement of the steroid hormone can be assigned a purpose, such as the mid-molecule OHgroup to form an intermolecular hydrogen bond with thymine, the end groups to forman ionic coupling with the phosphodiester backbone, and the internal structures, such asrings, methyl groups, and double bonds to enhance stability and interaction. Furthermore,the backside elements of the steroid hormones, such as an OH group, can influence thetranscription process. Indeed, these concepts have been applied to RNA based applicationsin forming an intermolecular bond with uracil in a like manner of thymine [28].As the interaction of binding the steroid molecule onto the strands of the DNA toinitiate strand separation, which would thereby enable replication and transcription, atype of molecular machine was synthesized. It can be envisioned that the DNA strands arein fluidic motion, and the pinching induced by the steroid elements, enabled a bubble tobe generated on either side of the interactive zone, which would permit access by chemicalreplicating agents. Depending upon the type of environment, the steroid triggering agentscan be evolved to permit directed or sustained replication periods. The transition to ionicbonding interaction of the phosphodiester chain of the steroid triggering molecule is anexample of the need for sustained interaction with the DNA strands. It is noted that theswitch to PO − from PO H came after the release of the triggering molecules because it isnot possible to associate two ions so close to each other without repulsion.In developing a research paper like this, it is appropriate to speculate on the issue ofevolution. The relative ease whereby the DNA sequence is built, merely by stacking pairedsteroid structures, and that the steroid molecules as genetic replication and transcription,which were enabled by simultaneous released to form the double helix thereby establish abeginning for life function, the probability of producing multiple starting sequences consis-25ent with different evolutionary pathways can be reasoned. Further, while the results weredeveloped such that the starting molecule was in the form of DNA, which permitted directcomparison, there is a potential likelihood that the first originating molecule of DNA didnot contain a multitude of nitrogenous groups. This more robust molecule would then takeon a master role from which images of it are developed to produce the nitrogenous structureof DNA as known today. Moreover, the conditions required for producing the structures,namely the polycyclic aromatic rings and hydrogen bonding, are ubiquitous, and thus it iseasy to imagine that such structures could be replicated in other environments besides thatof Earth, and thereby deposited on Earth, which would be consistent with the discoveriesof polycyclic aromatic hydrocarbons reported by the astrobiology community includingchrysene[29]. Thus, the process sequence results describing the origin of DNA as presentedin this article are not inconsistent with many of the philosophical and scientific tenets.As presented by the checklist in the introductory section regarding the requirements fora valid new theory on the creation of life, the theory of the origin of DNA developed in thisarticle satisfies each of the requirements. It is a truly remarkable that DNA nucleotidesand steroid molecules were developed as a unified complex, developed in an intermolecularmanner with each molecule influencing one another to enable a big bang, instantaneousmoment of the simultaneous synthesis of structure and function. Thus, as soon as thesteroid molecules are ejected from the DNA-steroid complex concurrent with the DNAnucleotides rotating into a position consistent with the double helix, a central life functionresults. • Molecular modeling software: The software program Avogadro was utilized to buildthe three dimensional molecular models. The Avogadro software program was usedto position the elements and calculate the bond distances. An optimization routinebased upon steepest descent was implemented to position the molecules automati-cally. Matlab was used to generate the energy dissipation requirements when theDNA nucleotides were connected by the steroid molecule. • Development of molecular models: The DNA nucleotides and steroid molecules weredeveloped and synthesized cooperatively in an intermolecular manner by stacking tenpairs which would result in TAGTC, which was selected to contain each letter andto arrange like and unlike molecules next to each other with respect to purines andpyrimidines. The intermolecular hydrogen bonds were configured, and then the opti-mization software was used to orient the molecules, positioning to minimize energy.After establishing the stack, the phosphodiester backbone was assembled startingfrom the bottom at molecule 1, and then linking 3, 5, 7 and 9 by forming the N-C-Ocoupling, which will ultimately correspond to the nucleotide to sugar link. Aftercoupling, the sugar molecule was formed. Both sides were completed, with hydrogen26onding stabilizing the steroid triggering molecule to the phosphodiester structure.The internal nitrogen elements of the purine and pyrimidine components of the nu-cleotide pairs were then positioned accordingly, and the bonds were broken with theaddition of oxygen groups selected at the appropriate position on thymine, cyto-sine, and guanine. The methyl group was added to thymine. The triggering steroidmolecule associated with cytosine was designed to have the appropriate triggeringmolecule. Other developments of the steroid triggering molecule were deemed out-side the scope of this study. The rotation was performed on the nucleotide pairs thathad a pyrimidine molecule on the 5’ phosphodiester side for this example, so as toeject the co-synthesized steroid molecules. Transcriptional positioning was performedby inserting the resultant steroid into the appropriate slot. For the ionic study, twoMg ions were also included. The optimization software was used to position thesteroid molecule. • Experimental: To obtain the relative activity of the synthetic steroids and steroidhormones, the literature was surveyed and representative values were selected for theactivity of prednisone, prednisolone, cortisol, and dexamethasone [30]. The experi-mental structures of these steroid hormones were then overlaid to the experimentalstructures of the A-T nucleotide pair to achieve a third hydrogen bond by intermolec-ular coupling. • Overall Procedure (journey): The development of this theory took the path of atop-down investigation. The initiating point was a mathematical analysis of a coor-dination of the nervous and cardiovascular systems to characterize a fever inducedby pneumococcal vaccination in conjunction with exercise [31]. An investigation intothe chemistry of the interaction resultant in the fever led to the concept of inhibitionof cortisol by prostaglandins, which also led to the concept of coupling two Ca ions at the glucocorticoid receptor to explain the differences in activity between thetwo molecules [32]. In further pursuit of a fundamental understanding of a feverresulted in transporting the glucocorticoid receptor to the nucleus to evaluate pos-sible transcription of cortisol and prostaglandins through ionic binding directly onthe DNA nucleotides. An evaluation of the structural symmetry of cortisol and theadenine-thymine base pair was determined, noting the intermolecular binding. Thusthe symmetry of steroid molecules and DNA nucleotides was discovered [21, 22, 23].This structural symmetry of steroid molecules and DNA nucleotides then led to thecurrent results to define a basis for the transcription results perceived of cortisol onadenine-thymine, and other potential interactions between RNA nucleotide and otherfunctional cyclic compounds. Hence, the original mathematical basis describing thesystems and cellular responses are consistent with the nuclear developments, and thusenable an integrated theory. 27 ppendix A Reaction Mechanisms Reaction mechanisms are indicated to form the differentiated molecular structures of: (a)adenine-thymine; (b) guanine-cytosine; (c) steroid type paired with A-T; (d) steroid typepaired with G-C. The pairing of steroid molecules and DNA nucleotides works both ways,which means that the orientation of the steroid molecule impacts the synthesis of the DNAnucleotides, and vice versa, since the interaction of two results in blocking elements whichprevent amination or reduction from occurring. This section is presented with an indica-tion of the synthesis steps that result in differentiating function, including the separationinto the base pairs. Then the suggested reaction steps for producing the final products isindicated, which includes the reduction of the steroid molecules. Finally, the common stepsare described, including the possible starting molecules from which the steroid moleculesresults. There are other synthesis pathways than the ones suggested in this section, how-ever, the overall logical sequence would be similar in terms of the transformation of themolecules into the final products. It is important to note that the synthesis steps occurwithin the same environment, such that while one base pairing is being synthesized, an-other aspect may be taking place in parallel, and thus the overall reactive environmentneeds to be consistent across most steps. At prebiotic conditions and environments, UVillumination will play a significant role and catalyze reactions for amination to take place atappreciable rates via free radical, photochemical reactions [33], as implied in the develop-ments of this section. In addition, as noted in Section A.1, the reactions take place withinthree dimensional constructs, although some mechanisms are presented in a standard twodimensional framework.
A.1 Enzymatic Coupling
As noted in reference [5], in the original work of Watson and Crick speculated that thedouble helix of nucleic acids may have an enzymatic nature; but that idea did not takehold and since then the research direction has trended toward the linear logic of a synthesisstarting from single-strand RNA nucleotides, which would ultimately lead to the DNAdouble helix complex. However, based upon the analysis presented in this research article, itis possible to re-evaluate the speculation of Watson and Crick within an analytic frameworkof the origination of DNA as an enzymatic construct of interleaved tetra-ringed structures,of which one section is covalently bonded to a phosphodiester backbone, while the adjacentstructure is connected through hydrogen bonding in close proximity.As indicated in Figure 17, the coordination of the paired building blocks enables asequence of effective reaction vessels, secured at the ends through phosphodiester cova-lent coupling, and through the center by hydrogen bonding to amino acids. This confinedenvironment enables the potential for an enzymatic capability in which the temporaryformation of bonding arrangements to permit intermolecular cyclic structures that can es-tablish element substitution, the degradation of chemical bonds to reduce intramolecular28tress, and the differentiation of the templates into their individual capacity as a nucleotidebase. While the structures did have aromatic stabilization, the intermolecular structuresmay also have benefitted from resonance stabilization, and thus the intermolecular con-straints to maintain an in-plane structure during the synthesis steps would have promotedthe present-day configuration in which the original aromatic structure was traded for anamine based self-assembled construct of a planar configuration.
A.2 Linking to the phosphodiester
In Figure 13, the method of linking stacks of molecules together is indicated, in which theenzymatic characteristics of the implicit reaction vessel are implemented. The initiatingstep involves the amination of what will be the steroid molecules, that is the non-nucleotidemolecule. This occurs at both ends of the molecule, in proximity to the diketone group onone side and the hydroxyl group on the other side, as indicated in Figure 13(a). Becausethis planar structure will enable a catalytic activity, the amine group reacts with bothof the ketone groups, and the amine group achieves alkene addition on either side of thephenol group, as shown in Figure 13(b), which then integrates within the DNA nucleotidemolecule, displacing the residual as methane and as methanol. This reaction is simliar tothe azofullerene synthesis [34, 35, 36]. The connection is then achieved by binding ontothe inserted amine groups, and then the formation of the sugar group to stabilize thephosphodiester backbone, as indicated in Figures 13(c) and 13(d), respectively.
A.3 Differentiation of A-T and G-C Templates
The implementation of this configuration involves intermolecular hydrogen bonding tocross-couple the two pairs, which is critical in defining the differentiation between A-T andC-G pairing. Since the ends are already coupled to connect the pairs, hydrogen bondingpairs are connected through the middle of the molecule. The ketone group is configuredtwo carbons away from the ketone group associated with the end-based pairing. Thisketone group is then connected to a hydroxyl group connected in proximity to the ketonegroup on the other molecule. The position of the ketone group relative to the adjacentsteroid molecule of the adjacent pair will define whether the molecule becomes A-T or G-C. Interestingly, the ketone group associated with the A-T pairing of the steroid moleculewill cross-couple to the nucleotide molecule and reduce the chances of amination fromoccurring, and thus arrive at an adenine. This is indicated in Figure 14(a) and (b) forG-C and A-T respectively, indicating the position. This is demonstrated by looking at theelectrostatic potential in Figure 14(c) and (d). This provides the underlying basis for thedifferences between A-T and G-C.In addition, this issue is also seen on the other side of the molecules, where the accessof the molecules, and their relationships between the paired relationship of the steroidmolecule to the nucleotide molecule, which will ultimately become the DNA nucleotide29 a) Amination (b) Connect (c) Separate (d) Bond
Figure 13: (a) To initiate the link of the phosphodiester backbone to the DNA nucleotides, the twoamine groups are attached to the molecule, which will become the steroid molecule. (b)a binding is achieved to replace the alpha carbon between the diketone groups, and onthe other end, the carbon binding to the hydroxyl group is replaced. (c) after binding,there is tendency for leveling with respect to the steroid molecules above and below themolecule where the amine group was replaced. (d) the final orientation, and ready forfurther amination and separation. base pairing. In Figure 15(a) and (b), the other side of the steroid - DNA complex isindicated. The electrostatic potential indicates the interaction of the steroid agents andthe molecule that will become the DNA nucleotides in Figure 15(c) and (d) for the G-Cand A-T pairings. In addition, the pairings for C-G and A-T also show similar results,both on the front side and the back side.
A.4 Procedure
In binding the phosphodiester backbone prior to its disassociation, as shown in Figure 16,of which the binding occurs at both ends of the nucleotide molecules 1, 3, 5, 7 and 9,while hydrogen bonding stabilizes the steroid molecules 2, 4, 6 and 8. Note that phosphorgroup contains both OH and an O, such that hydrogen bonding can be achieved at bothends of the steroid molecule: one side of the steroid molecule contains an OH group whichwill hydrogen bond with the O element of the phosphate group, and on the other side,the steroid molecules comprises a ketone group which will hydrogen bond to the hydroxylgroup of the phosphate group. The conversion of the link to a nitrogen element is indicated,and the binding occurs either at the middle carbon located between two ketone groups ofthe six-membered ring, which is discussed in the subsequent sections. It is noted that thereis sufficient space for occupation of the steroid structure in between each DNA nucleotide,30 a) G-C (b) A-T(c) G-C (d) A-T
Figure 14: (a) For G-C, the orientation of the steroid molecule, second from the bottom, withrespect to the molecule that will become a G-C nucleotide is oriented such that aminationis possible on the leading element of guanine, as initiated through UV illumination.Thus, an NH group will be affiliated with the leading side of guanine. (b) For A-T, however, there is a connecting group of O-OH associated with the steroid moleculepairing, thus amination is not possible. Ultimately, this is why A-T has two internalhydrogen bonds, while G-C has three. (c) The electrostatic potential indicates that thesteroid molecule will not influence the G-C amination. (d) The electrostatic potentialindicates the coupling with the steroid molecule which will prevent amination for A-T. as both structures are relatively planar.Continued amination, oxidation, and reduction steps are performed to complete theco-synthesized fabrication of not only the encoded DNA nucleotides, but also the steroidmolecules. These steps are described in the following section. Interestingly, at the end ofthe synthesis steps, the steroids are released from the unified complex when the pyrimidinemolecules on the 5’ side rotate into position to form the double helix. Thus, there isa culminating step to the synthesis which brings both molecules to life, as the steroidmolecules can interact with the DNA double helix to enable replication and transcription.The overall procedure to produce a differentiated structure is indicated in Figure 1731 a) G-C (b) A-T(c) G-C (d) A-T Figure 15: On the other side of G-C relative to Figure 14(a), the orientation of the steroid molecule,second from the bottom, with respect to the molecule that will become a G-C nucleotideindicates potential influence over the oxidation and amination. (b) For A-T, there islittle association with the backside other than a potential hydrogen bond, and thus ox-idation will be effective at the thymine molecule side. (c) The electrostatic potentialindicates that the steroid molecule will influence the G-C association on the backside.(d) The electrostatic potential indicates the coupling with the steroid molecule will influ-ence oxidation for A-T. for the adenine-thymine pairing. In Figure 17(a), the differentiation and separation of theDNA nucleotides is seeded by the amination onto the alpha hydroxy of the steroid molecule,with subsequent attack to the DNA nucleotide in a position to aminate the rings of thepurine molecules. Figure 17(b), an amination at the steroid and a coupling to the C ringof the DNA nucleotide, when still intact is achieved to initiate the separation. Figure 17(c)completion of the amination, and decoupling of the B ring with oxidation onto thyminecompletes the process. Figure 17(d), with the removal of the ethene molecules, there is selfalignment of the pairs to complete the transformation32 igure 16: Model indicates the paired synthesis of the steroid molecules and the DNA nucleotidesduring a stage of fabrication where the DNA nucleotides are formed, but not yet separatedinto their basic base pairing with associated hydrogen bonding. There is interaction withthe steroid molecule during the formative stages, and the DNA nucleotides influencethe formation of the steroid molecule, and the steroid molecule influences the DNAnucleotides. The association with amino acids is not included here.
A.5 Separation into A-T and G-C Templates
As indicated in Figure 18(a), the reaction mechanism suggested for the formation ofadenine-thymine is indicated. It is important to note that this reaction takes place inconjunction with pairing to the steroid molecule, which has hydrogen bonding to the frontportion of the adenine-thymine group, which prevents amination from occurring on theadenine front side. This provides a key differentiating step. In addition on the backside,the interaction leads to the preference for oxidation on the thymine side. Aminations inan ammonia environment, with availability to oxidation components is performed. Theentire structure is under stress, in which there is a significant driving force to form thedouble helix, and thus enable the separation of the base pairs. For the G-C base forma-tion, the suggested reaction mechanism and strategy is indicated in Figure 18(b), whichoccurs within the same environment as that of A-T. Recall that because of the pairedsteroid molecule positioning of its ketone elements, it is possible to aminate the front ofthe molecule, and thus there is amination on guanine. This enables the oxidation at thethymine side. As with A-T, the separation is driven by the drive to form the double helix,and its lower energy state.Thus, this provides the basic answer as to why the A-T pairing only has two internalhydrogen bonds, while the G-C pairing has three internal bonds: because of the relativeorientation of it to the paired steroid molecule permits hydrogen bonding. Moreover, it33 a) Initial (b) Bonding (c) Aligning (d) Final
Figure 17: (a) The differentation and separation of the DNA nucleotides is seeded by the amina-tion onto the alpha hydroxy of the steroid molecule, with subsequent attack to the DNAnucleotide in a position to aminate the rings of the purine molecules. (b) An aminationat the steroid and a coupling to the C ring of the DNA nucleotide, when still intact isachieved to initiate the separation. (c) Completion of the amination, and decoupling ofthe B ring with oxidation onto thymine completes the process. (d) with the removal ofthe ethene molecules, there is self alignment of the pairs to complete the transformation. indicates why the overall structure of the base pairings occurs, and provides the drivingforce for it to occur, high stress, and a significant reduction in energy by transitioning toa double helix form. It will also provide answers to why NH2 is on the pyrimidine purineside for G-C but on the purine side for A-T, and other such comparative matters. It isimportant to note that these reactions are effectively taking place over the entire molecule,so the same process steps have to be addressed concurrently on how they would react toA-T if working on C-G, for example. A.6 Differentiated Final Products
The final steps to produce the final products are all performed in the same reducing andmethylation environment. In Figure 19 the steps to reduce the oxygen group on thymine isindicated followed by the methylation to form the methyl group associated with thymine.Since the oxygen group of thymine is not engaged in hydrogen bonding and has an adjacentavailable carbon segment, this will allow for its reduction. In Figure 19(b) the reactionsequence is indicated to reduce the oxygen functional group of what will become cytosine.The positioning of the oxygen group enable its reduction, whereas the other segments areengaged with the guanine base, and thus do not undergo reduction.34 a) Formation of A-T(b) Formation of G-C
Figure 18: (a) For the A-T base formation, it is important to recall the result that indicated becauseof the paired steroid molecule positoning of its ketone elements, it is not possible theaminate the front of the molecule, and the amination occurs on the purine side, adenine.This enables the oxidation at the thymine side. The separation then occurs though anamination on both sides of the molecule, with the double bond established on adenine.(b) For the G-C base formation, it is also important to recall the result that indicatedbecause of the paired steroid molecule positioning of its ketone elements, it is possible toaminate the front of the molecule, and the amination occurs on the purine side, guanine.This orientation also enables the oxidation at the guanine side, and hence amination atthe cytosine side. The separation then occurs though an amination on both sides of themolecule, with the double bond established on cytosine.
Finally, and in parallel, in Figure 20(a) the steroid resultant in the corticosteroid func-tion is indicated, as it will also undergo reduction and methylation, while the thymine andcytosine groups are reduced. Because a portion of what will become the corticosteroidmolecule is engaged in hydrogen bonding with A-T, it will survive the reduction process.While in Figure 20(b), those molecules associated in hydrogen bonding with C-G will bereduced, and thus not contain a oxygen group. Hence, there are two types of steroidmolecules produced: one associated with A-T and T-A, and the other associated with G-Cand C-G. 35 a) Formation of Thymine(b) Formation of Cytosine
Figure 19: (a) Steps to reduce the oxygen group on thymine and the methylation to form the methylgroup associated with thymine. The oxygen group of thymine is not engaged in hydrogenand has an adjacent available carbon segment which will allow for its reduction. (b) Thereaction sequence reducing the oxygen functional group of cytosine. The positioning ofthe oxygen group will enable its reduction, whereas the other segments are engaged withthe guanine base.
A.7 Starting Materials
To broaden the scope, the developments will consider a related structured, the fused aro-matic four ring structure of chrysene, indicated in Figure 21(a), which is a relatively simpleorganic structure. From a structural perspective, the molecule can be aligned with itselfunder several different configurations, rather than just one if it were to be linear. It is alsoa stable compact structure, and further is the same general structure of a steroid molecule,is consistent with the general structure of both the DNA nucleotide pairs and the steroidhormones. With the addition of the functional groups to chrysene, stacking of the moleculescan be secured through attraction of the alpha acidic group situated in between the twoketone molecules. Further, this molecule is active and can be reduced as indicated Figure21(b), which would be enabled through a catalyst, as with all the reactions, and includesphotochemical effects.
A.8 Ionic Binding
As indicated earlier, the original DNA was of a phosphate that had an OH group insteadof oxygen ion. The hydrogen group was used for hydrogen bonding to the steroid molecule,36 a) Steroid for A-T pairing(b) Steroid for G-C pairing
Figure 20: (a) For the steroid molecule paired with A-T, the reduction and methylation will takeplace on areas that are not protected by the interaction with A-T. This will result in thereduction of double bonds and elimination of some of the oxygen functional groups. Theends will remain intact since there is hydrogen bonding interaction with the phosphodi-ester backbone. (b) A similar result is obtained for the steroid molecule paired with C-G,except that because the mid-molecule oxygen groups are not engaged with C-G, they willbe reduced. Hence, there are two types of steroid molecules produced. which contained a ketone end group as well as a hydroxyl end group. However, modernexaminations of the DNA molecule assign the phosphate group as PO − an ionized repre-sentation. Thus, apparently there is a slight shift of the DNA molecule from transcriptionthrough hydrogen bonding of the steroid element to the ionic bonding of the phosphategroup, which is much stronger, and this structure will be used here to evaluate DNA tran-scription. For the modern representation to indicate its usage with Mg ions, of whichother ions can be utilized of a positive two charge to link with adjacent phosphate groups,and include Ca , Mn and Zn . In Figure 22(b), the intermolecular hydrogen bond-ing between the steroid molecule and the thymine-adenine pairing is indicated throughexamination of the electrostatic potential. The intermolecular hydrogen bonding betweenthe steroid molecule is indicated, which is 1.827 ˚A. The ionic binding is tight, with thedistance between the ion to the steroid group, for example the ketone group is 1.972 ˚A andthe oxygen element of the phosphodiester backbone is 1.699 ˚A and 1.673 ˚A, as indicated in22(c) and (d). For the simulation results, the energy of the complex prior to binding was37 a) Conversion of chrysene(b) Steroid complex Figure 21: (a) Conversion of chrysene to a diketone on both sides of the molecule. In betweenthe ketone groups are acidic hydrogens. (b) The reaction to reduce the chrysene basedstructure to the steroid structure is indicated. -1,161 kJ/mol, and after binding, it was -9,010 kJ/mol, thus providing for 7,849 kJ/mol ofenergy to dissipate through bond breaking. (a) Internal Hydrogen Bond (b) Electrostatic Po-tential (c) Ionic Binding (L) (d) Ionic Binding (R)
Figure 22: (a) Intermolecular hydrogen bonding distances are achieved by the steroid to thyminecoupling, as well as the internal thymine to adenine hydrogen bonding. (b) The elec-trostatic potential of the intermolecular hydrogen bond between the steroid triggeringmolecule and thymine is indicated, along with the internal two hydrogen bonds of ade-nine to thymine. (c) Ionic coupling of the end group of the steroid molecule, which willactually be a steroid hormone is achieved. (d) The two end groups of the steroid moleculeare ionically coupled to the nucleotide pairs through adjacent phosphodiester groups. ppendix B Conflicts of Interest No external funding was used for this research.
Appendix C Provisional Patents
The author has filed several personal provisional patents associated with this line of re-search. These provisional patents include:1. Charles Schaper, “Binding Steroid Molecules to DNA”, Provisional Patent: US62/977,216. Filed 3/9/2020.2. Charles Schaper, “Binding Nucleic Acids”, Provisional Patent: US 63/016,446. Filed5/5/2020.3. Charles Schaper, “Synthesis of Genetic Structures”, Provisional Patent: US 63/027,320.Filed 5/19/2020.4. Charles Schaper, “Design of DNA, Genetic Codes, and Life Function”, ProvisionalPatent. Ref: E20206R233375951. Filed 6/28/2020.39 ppendix D Description of Book Contents • Discovering the Primer of DNA - The basic discovery process that I made to identifythe common structure of a steroid molecule embedded within each DNA nucleotidepair, the structural match of steroid hormones to DNA structure, and its correlationin function of an intermolecular bond to pharmacological efficacy. • Encoding DNA - The encoding of a unified complex, originally synthesized throughintermolecular coupling of a pair of hydrogen bonded steroid structured molecules isdescribed. • Transmitting DNA - The transmission of the encoded complex through the formationof a DNA double helix and steroid molecules which provide access to the informationcontent contained within the double helix. • Decoding DNA - The processes of decoding the double helix structure through thefunction capability provided by the steroid molecules, including decoding tables ofan interaction vessel formed by the steroid molecules. • Translating DNA - The mapping of the nucleotide triplet to amino acid is shownthrough the analysis of the structural and chemical characteristics of the DNA doublehelix formed in conjunction with the steroid molecules. • Example - An example is provided of constructing a protein chain of seven aminoacids, including the encoding, transmission, decoding and translation aspects. • Replication - Replication of the double helix through the steroid molecules is shown,along with error correction procedures.40 ibliographyibliography