(This is a technical post. Please see paper or search for terms and references. Feel free to leave a comment if anything is unclear. And lest y’all think I’m talkin’ smack here, please know that my research career started by studying histone modification and chromatin structure and function.)
A fundamental unanswered question in the annals of biology is this: How did DNA emerge in the Universe? The RNA world hypothesis basically posits that RNA emerged prior to protein and that proteins emerged prior to DNA. The extant biochemical evidence supports this proposal. Making DNA from scratch is known to require three main protein classes: ribonucleotide reductase, phosphoenzymes, and nucleic acid binding proteins. To these I turn.
Major Protein Classes
1. Ribonucleotide reductases. Chemically, RNRs are enzymes that convert a ribonucleotide to a deoxyribonucleotide by abstracting the 2′ OH (hydroxyl). This is written like this:
NDP → dNDP
Where the ‘d’ represents the deoxy form of the nucleotide, and NDP represents ADP, GDP, CDP, and UDP and dNDP represents dADP, dGDP, dCDP, and dTDP (dUMP → dTMP). In order to convert the dNDP molecule to a form that can be used in DNA replication, it must undergo phosphorylation.
2. Phosphoenzymes. A particular type of phosphoenzymes, dNDP kinases, is required to establish and maintain a pool of dNTPs that are a requisite for making DNA. This can be chemically written in the following manner:
dNDP + ATP → dNTP + ADP
Phosphotransferases are responsible for moving the orthophosphate to and from NTPs (ATP shown here) to deoxynucleotide monophosphates (not shown) and diphosphates. In other words, to build and thermodynamically maintain a pool of dNTPs, I employ and am this enzyme class. Other important phosphoenzymes are phosphatases, nucleases, ligases, topoisomerases (also called gyrases), and, importantly, a little group of proteins called polymerases.
3. Nucleotide and nucleic acid binding. This class of polypeptides are not enzymes per se but rather play a fundamental structural and organizational role for deoxynucleotides and deoxynucleotide polymers in vivo. In eukaryotes, a well-known group of these polypeptides are histones – aka nucleotide chaperones.
From a theoretical standpoint, these three protein classes emerged in the secondary aminogyre and are responsible for the trimergence of the deoxynucleotide (symbolized by D) – and dNTP construction, destruction, and maintenance. These three are thus quantized as aminons (A, the theoretical symbol and term to identify aminogyre quanta, also known as polypeptides) that clearly toggle between synthesis and decay, activity and inactivity, folding and unfolding, assembly and disassembly, and nuclear and cytoplasmic occupancy. Like all aspects of the Universe, these aminons can be studied in isolation, but this excludes information about their metabolic life cycle.
Understanding the emergence and existence of deoxynucleotides in the Universe is theoretically modeled by the genogyre (originally called the deoxygyre).
The primary genogyre is D•3A ← → D•2A + A (Figure 1A).
The secondary genogyre is D•3A ← → [D•A]n + 2A (Figure 1B).
The tertiary genogyre is D•3A ← → D + 3A (Figure 1C).
Again, I use the theoretical shorthand A to refer to the three classes of polypeptides quantized as aminons, with three being noted as 3A. A1 is RNR, A2 is phosphoenzyme, and A3 is chaperone. The quantized genomic material (deoxynucleotide, gene, genome) is given the symbolic D (Fig. 1D; originally deoxyon in draft, changed to a genon for the paper).
Fitting the Theory to the Data
In biological reality, dNTP only comes into existence and is found in association with and because of these three proteins (chaperone, the RNR, and phosphotransferase), this is modeled as D•3A. The primary genogyre (Fig. 1A) models the following interconversion: D•3A is the high energy, learning, unstable state (genognose) as the phosphotransferase, having performed its catalytic role, is evicted or displaced.
The dNTP falls to dNTP (D•2A) a lower energy, relativistically stable, memory state (genomneme) where it stably resides in association with RNR (empirically verifiable as RNR is able to chemically “sense” levels of dNDPs and dNTPs in vivo) and in association with chaperones (for storage and immediate deposition onto DNA during repair and recombination).
The aminon, being the singularity of the genogyre, exerts the thermodynamic attractorepulsive, creatodestructive, and expansocontractive forces on the particles in the genogyre.
The secondary genogyre (Fig. 1B) models how DNA emerged in the Universe and how new DNA sequences (genes, intragenic regions, promoter and enhancer elements, telomeres, centromeres, transposable elements, etc.) emerge.
Here the 2A models the two displaced aminons: RNR and the phosphoenzyme, which is required for forming the dNMP polymer. So, as modeled here, the formation and modification of a DNA sequence is a ribon (RNA)-templated aminon (protein)-mediated phenomenon that chemically involves condensation of the phosphodiester bond, requiring both the phosphogyre and the oxygyre.
Although the chemical bond between the deoxynucleotides is the orthophosphate, the molecular link between the dNMP polymer is the retained aminon – in eubacteria this models nucleoid proteins and in eukaryotes and archaebacteria it models histones and HMG proteins, for example.
Hence, [D•A]n is a polymer of dNMPs known as a single strand of DNA. The antiparallel nature of DNA is parsimoniously modeled by antiparallel genogyres – just like two antiparallel bar magnets (antiparallel electrogyres). Moreover, as a corollary to the fifth gyraxiom, the deoxynucleotide can exist either in the free state or in the polymerized state, but not both states at the same time. Finally, the stability, plasticity, and memory of DNA is also modeled by the secondary genogyre.
The tertiary genogyre (Fig. 1C) models, as D in the gyrobase, the accumulation of a pool of deoxynucleotides that are used as cofactors in biochemical pathways and – more importantly – the deoxynucleotides that are thermodynamic driving force in the process known as semi-conservative DNA replication. Note, in this regard, that the accumulated deoxynucleotides reach a critical carrying capacity, modeled by the genon (quantized D, Figure 1D; although I should mention that the genon can be used to represent one or more genogyres), eliciting DNA replication: 1D → 2D. In other words, rather than trimergence, it is a dimergent phenomenon.
How DNA Originates and Organizes; How I Change My DNA
In sum, the genogyre models the origin, nature, and evolution of deoxynucleotides and DNA in all living systems that exist now or have ever existed in the evolutionary history of the Universe. The genogyre models both the microcosm—that is, the DNA that exists in each and every one of the cells in your body, my body, or any body—and the macrocosm—the DNA that exists throughout the entire Universe, be it in a cell, a virus, a vesicle, in solution, or in space. In other words, the DNA in your body, whenever you make it, not only recapitulates the origin of DNA in the Universe, but is the origin of DNA in the Universe.
This resolves the long-standing question at the beginning of this post about DNA.
Moreover, it provides the true model for understanding the transfer of genetic information, replacing the outdated, incomplete, and incorrect central dogma. Thus, consistent with all of the empirical evidence, RNA came first, then protein, then DNA, as modeled by the ribogyre (ribon) being within the aminogyre (aminon), which is within the deoxygyre.
Empirical evidence of the gyratory impact of the dextral aminogyre is that DNA is only found in B-form DNA, which spirals exclusively right-handedly in living cells (Figure 2); this is because of the sixth gyraxiom. Moreover, as a corollary to the seventh gyraxiom, maintaining homeostasis within, between, and among gyre systems is revealed by the chiral inversion of DNA as it wraps around the nucleosome levorally (Figure 3).
I should mention one last thing about how I became and am DNA. Mutations in DNA – single or mutliple nucleotide changes – are not “random.” As modeled by the secondary genogyre and the complete and consistent theory, I change the deoxynucleotides in My DNA the same way I change words in this sentence: I decide what to take out and what to put in.