RNA–DNA Chimeras in the Context of an RNA World Transition to an RNA/DNA World

Gavette, Jesse V.; Stoop, Matthias; Hud, Nicholas V.; Krishnamurthy, Ramanarayanan

doi:10.1002/ange.201607919

Cited by 13 publications

(47 citation statements)

References 50 publications

(71 reference statements)

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“…It should be noted that the shown mechanism bears a strong similarity to chemical systems that were able to amplify a bias between chiral molecules 54 . We therefore hypothesize that the concentration dependence of the ligation network could also purify backbone heterogeneity based on their differential duplex stability 55 .…”

Section: Discussionmentioning

confidence: 99%

Cooperative Ligation Breaks Sequence Symmetry and Stabilizes Early Molecular Replication

Toyabe

Braun

2019

Phys. Rev. X

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Each living species carries a complex DNA sequence that determines their unique features and functionalities. It is generally assumed that life started from a random pool of oligonucleotides sequences, generated by a prebiotic polymerization of nucleotides. The mechanism that initially facilitated the emergence of sequences that code for the function of the first species from such a random pool of sequences remains unknown. It is a central problem of the origin of life. An interesting option would be a self-selection mechanism by spontaneous symmetry breaking. Initial concentration fluctuations of specific sequence motifs would have been amplified and outcompeted less abundant sequences, enhancing the signal to noise to replicate and select functional sequences. Here, we demonstrate with experimental and theoretical findings that templated ligation would provide such a self-selection. In templated ligation, two adjacent single sequences strands are chemically joined when a third complementary strand sequence brought them in close proximity. This simple mechanism was a likely side-product of a prebiotic polymerization chemistry once the strands reach the length to form double stranded species. As shown here, the ligation gave rise to a nonlinear replication process by the cooperative ligation of matching sequences which self-promoted their own elongation. This led to a cascade of enhanced template binding and faster ligation reactions. A requirement was the reshuffling of the strands by thermal cycling, enabled for example by microscale convection. By using a limited initial sequence space and performing long term ligations, we found that complementary sequences with an initially higher concentration prevailed over either non-complementary or less concentrated sequences. The latter died out by the molecular degradation that we simulated in the experiment by serial dilution. The experimental results are consistent with both explicit and abstract theory models that were generated considering the ligation rates determined experimentally. Previously, other nonlinear modes of replication such as Hypercycles have been discussed to overcome instabilities from first-order replication dynamics such as the error catastrophe and the dominance of structurally simple, but fast replicating sequences, known as the Spiegelman problem. Assuming that templated ligation was driven by the same chemical mechanism that generated prebiotic polymerization of oligonucleotides, the mechanism could function as a missing link between polymerization and the self-stabilized replication, offering a pathway to the autonomous emergence of Darwinian evolution for the origin of life.

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Section: Discussionmentioning

confidence: 99%

Cooperative Ligation Breaks Sequence Symmetry and Stabilizes Early Molecular Replication

Toyabe

Braun

2019

Phys. Rev. X

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“…The Krishnamurthy group has recently proposed a similar pathway leading from an initially heterogeneous set of templates to an increasingly homogeneous set of replication products. 26 , 47 , 48 In their case the physical mechanism leading to homogeneity is different, and is based on the surprising observation that homogeneous all-RNA or all-DNA oligonucleotides bind more strongly than do otherwise identical but heterogeneous oligonucleotides to complementary but heterogeneous templates. As a result of the stronger binding, the template-directed ligation of all RNA or all DNA oligonucleotides is favored over the ligation of mixed oligonucleotides, such that over repeated cycles of ligation-mediated replication, relatively homogeneous replication products should emerge.…”

Section: Discussionmentioning

confidence: 99%

“… 14 Long before recent suggestions of prebiotic routes to the 2′-deoxyribonucleotides, 16 , 23 these DNA building blocks were known to be less effective than ribonucleotides in nonenzymatic template copying reactions. 24 However, recent work showing that mixed ribo/deoxy oligonucleotide duplexes have much lower melting temperatures than either homogeneous RNA or DNA duplexes 25 , 26 suggests that this heterogeneity might facilitate replication by enhancing strand separation. Given the wide range of effects of noncanonical nucleotides on nonenzymatic template directed copying chemistry, a systematic study of the effects of prebiotically plausible variant nucleotides on copying chemistry is needed in order to understand if and how more homogeneous modern RNA could have arisen from complex prebiotic mixtures of nucleotides.…”

Section: Introductionmentioning

confidence: 99%

A Model for the Emergence of RNA from a Prebiotically Plausible Mixture of Ribonucleotides, Arabinonucleotides, and 2′-Deoxynucleotides

et al. 2020

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The abiotic synthesis of ribonucleotides is thought to have been an essential step toward the emergence of the RNA world. However, it is likely that the prebiotic synthesis of ribonucleotides was accompanied by the simultaneous synthesis of arabinonucleotides, 2′-deoxyribonucleotides, and other variations on the canonical nucleotides. In order to understand how relatively homogeneous RNA could have emerged from such complex mixtures, we have examined the properties of arabinonucleotides and 2′-deoxyribonucleotides in nonenzymatic template-directed primer extension reactions. We show that nonenzymatic primer extension with activated arabinonucleotides is much less efficient than with activated ribonucleotides, and furthermore that once an arabinonucleotide is incorporated, continued primer extension is strongly inhibited. As previously shown, 2′-deoxyribonucleotides are also less efficiently incorporated in primer extension reactions, but the difference is more modest. Experiments with mixtures of nucleotides suggest that the coexistence of riboand arabinonucleotides does not impede the copying of RNA templates. Moreover, chimeric oligoribonucleotides containing 2′deoxy-or arabinonucleotides are effective templates for RNA synthesis. We propose that the initial genetic polymers were random sequence chimeric oligonucleotides formed by untemplated polymerization, but that template copying chemistry favored RNA synthesis; multiple rounds of replication may have led to pools of oligomers composed mainly of RNA.

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“…Based on the present and previousassessments [35][36][37][38][39], quantum information processing [40][41][42][43][44][45] exhibited by prokaryotic [15][16][17]20,21] and eukaryotic [47][48][49][50][51][52][53][54] genomic systems can be evolutionarily explained in terms of EPR-generated [29][30][31] entangled proton qubits originating in primordial RNA -ribozyme duplex segments [35,36,[57][58][59][60][61][62][63], which subsequently were quantum mechanically processed by Grover's-type [40] quantum readers. The molecular genetics history of observing [18][19][20][21][22][23][24][25], but misidentifying, time-dependent EPR-generated [29][30]…”

Section: Introductionmentioning

confidence: 99%

“…Successful implementation of Grover's [40] processors executing quantum information processing of EPRgenerated [29][30][31], entangled proton qubits in ancient [46] T4 phage [15][16][17] and modern eukaryotic [37][38][39]54] systems argues that "ancient" quantum transcription of entangled proton qubits [35,36], and attendant translation, antedate "standard" classical transcription [28] of genetic information where "evolved" translation [57] is executed in terms of fully developed ribosomes with tRNAs, etc. In this case, ancestral ribozyme -RNA duplex systems [35,36,[58][59][60][61] acquired rudimentary quantum processing [40] abilities to implement quantum transcription, and attendant translation, of EPR-generated [29][30][31] entangled proton qubits, and consequently, such ancestral genomic systems would not necessarily be evolutionarily terminal as concluded by Koonin's [57] classical assessments.…”

Section: Introductionmentioning

confidence: 99%

EPR-Proton Qubits’ Role in Evolution and Age-Related Disease

W¹

2017

PSBJ

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Earth's surface acquired necessary life-giving volatile elements carbon, nitrogen, and sulfur from a collision with a Mercury-like planetary embryo ~ 4.4 billion y ago. Icy comets containing hydrocarbons collided with a cooling prebiotic Earth to create impact reactive environments that via classical anthropic causality introduced primordial "ribozyme-like" RNA complexes which could duplicate a few molecular units/24 hrs. Random classical processes introduced energetically accessible duplex RNA segments containing keto─amino (─NH2) hydrogen bonds, where hydrogen bonded amino protons encountered quantum uncertainty limits, Δx Δpx ≥ ħ/2. This introduced probabilities of EPR-arrangements, ketoamino-(entanglement) → enol−imine, where reduced energy product protons are each shared between two different indistinguishable sets of electron lone-pairs belonging to enol oxygen and imine nitrogen on opposite genome strands. Product protons participate in entangled quantum oscillations at ~4×10 13 s −1 (~ 4800m s −1) between near symmetric energy wells in decoherence-free subspaces until measured, δt << 10 −13 s, in a genome groove, ~12 or 22Å, by selected Grover's quantum bio-processors. Analyses imply entanglement origins of the triplet code, 4 3 codons, specifying ~ 22 L-amino acids. Entanglement resources provided a sequence of ~ 12 incremental entanglement-enabled improvements to genome fitness, of the form: RNA-ribozyme → genetic code origin → RNA-protein → DNA-protein. An EPR-entanglement algorithm explains "probabilistic" genomic growth over the past ~ 3.610 9 y from duplex RNA-ribozyme segments, into a DNA double helix of ~ 6.810 9 bp. Entangled proton "qubit pairs" are the smallest "measurable" genetic informational unit, specifying evolution instructions with "measured" quantum information. This EPR-entanglement model accurately predicts microsatellite evolutionary distributions in rat and human genomes. Consistent with preserving "wild-type" gene pool viability, Huntington's and other age-related human diseases are phenotypically expressed by Grover's quantum processors, measuring quantum informational content of entangled proton qubits occupying a "threshold limit".

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RNA–DNA Chimeras in the Context of an RNA World Transition to an RNA/DNA World

Abstract: Scheme 1. The RNA world concept. a) Transition from ah omogeneous RNA backbone to ah omogeneous DNA backbone is assumed during the invention of DNA by RNA, b) without consideration of the role of heterogeneous backbone chimeric sequences that would be formed.[*] Dr.

Cited by 13 publications

References 50 publications

Cooperative Ligation Breaks Sequence Symmetry and Stabilizes Early Molecular Replication

Cooperative Ligation Breaks Sequence Symmetry and Stabilizes Early Molecular Replication

A Model for the Emergence of RNA from a Prebiotically Plausible Mixture of Ribonucleotides, Arabinonucleotides, and 2′-Deoxynucleotides

EPR-Proton Qubits’ Role in Evolution and Age-Related Disease

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