PREreview del Problem-Solving Nucleic Acid-Based Prebiotic Entities as Origin of Life

Short summary of the research and contribution to the field

This hypothesis paper proposes that early DNA/RNA-based molecular systems acted as prebiotic “problem-solving” entities that stored information, replicated, generated functional products, and underwent selection-like processes before the emergence of cellular life. The author argues that double-stranded linear DNA may have served as a stable information-storage molecule, while RNA contributed to replication, transcription, stem-loop RNA self-replication, reverse transcription, and the early development of translation. The manuscript also proposes a simplified origin of the translation system through highly relaxed wobble recognition involving only two primitive tRNAs.

The paper is ambitious and conceptually interesting because it attempts to connect DNA stability, RNA catalytic function, primitive replication, codon-table structure, reverse transcription, and molecular selection into one origin-of-life scenario. However, many of the central claims are speculative and need clearer separation from experimentally established evidence.

Positive feedback / strengths

1. Original and ambitious hypothesis. The manuscript presents a broad, integrated model for how DNA and RNA may have become functionally interdependent before modern life.

2. Useful conceptual framework. The proposed roles of information, storage, instruction, tools, resources, products, and feedback provide a structured way to think about prebiotic molecular systems.

3. Interesting DNA/RNA interdependence model. The paper usefully emphasizes that DNA may provide long-term information storage while RNA may contribute functional and catalytic roles.

4. Thought-provoking translation model. The two-primitive-tRNA wobble-recognition hypothesis is creative and could stimulate useful discussion, although it requires much stronger support.

5. Figures help explain the hypothesis. The diagrams of DNA/RNA replication, stem-loop RNA, reverse transcription, codon recognition, and pre-life evolution are helpful for understanding the proposed model.

Major issues

1. Separate established evidence from speculation

The manuscript sometimes presents speculative steps as if they are strongly supported. The author should clearly label which points are experimentally established, which are plausible inferences, and which are untested hypotheses.

Suggested improvement: Add a table separating: Established facts | Supported inferences | Speculative assumptions | Testable predictions.

2. Reframe “problem-solving” and “intelligence” language

The terms “problem-solving,” “intelligence,” and “self-beneficial” risk anthropomorphizing abiotic chemistry.

Suggested improvement: Clarify that these terms are used as metaphors or formal systems concepts, not intentional cognition. A more precise phrase would be “selection-like persistence of self-propagating molecular systems under environmental constraints.”

3. Strengthen prebiotic chemistry assumptions

The model depends on the availability of DNA, RNA, ribonucleotides, deoxyribonucleotides, primers, phosphate-activating agents, and calm environments. These assumptions need stronger chemical support.

Suggested improvement: Discuss how deoxyribonucleotides, ribonucleotides, activated phosphate chemistry, ribose/deoxyribose, and N-cyanoimidazole-like agents could plausibly coexist at useful concentrations under prebiotic conditions.

4. Provide stronger support for bidirectional nonenzymatic DNA synthesis

A major claim is that prebiotic DNA replication could occur bidirectionally from primers and short nucleotide blocks. This is central to the model but not directly demonstrated.

Suggested improvement: Provide stronger evidence or propose experiments testing RNA/DNA primer-mediated nonenzymatic bidirectional synthesis, replication fidelity, strand separation, and full-length product formation.

5. Discuss competing RNA-world and coevolution models

The paper should engage more directly with existing origin-of-life theories.

Suggested improvement: Compare the proposed model with the RNA world, DNA/RNA coevolution, metabolism-first models, lipid/protocell models, peptide-RNA coevolution, mineral-surface chemistry, hydrothermal vent models, and wet-dry cycle polymerization.

6. Clarify the “calm environment” model

The manuscript repeatedly relies on calm, ribonucleotide-rich or deoxyribonucleotide-rich environments, but these are not clearly defined.

Suggested improvement: Define temperature, pH, ionic conditions, wet-dry cycling, mineral surfaces, nucleotide concentration, UV exposure, and how such environments would support replication, transcription, and reverse transcription.

7. Be more cautious about linear double-stranded RNA as a “replicative dead end”

The claim that linear dsRNA cannot replicate prebiotically should be softened because other RNA-world models propose alternative mechanisms.

Suggested improvement: Discuss ribozyme-mediated replication, strand displacement, compartmentalization, mineral catalysis, and wet-dry cycling as possible alternative or competing mechanisms.

8. Strengthen the two-tRNA translation hypothesis

The two-tRNA model is creative but highly speculative. It needs structural, biochemical, and computational support.

Suggested improvement: Explain whether two broadly specific tRNAs could realistically support meaningful peptide synthesis, whether early peptides based mainly on hydrophobic/hydrophilic patterning could have selectable function, and whether expanded wobble recognition across multiple codon positions is structurally plausible.

9. Address compartmentalization and genotype–phenotype linkage

The model assumes that products made by DNA/RNA entities benefit the same entities that encoded them. Without compartmentalization, this linkage is difficult to maintain.

Suggested improvement: Discuss protocells, coacervates, mineral surfaces, gels, membranes, or spatially restricted environments that could keep nucleic acids, RNAs, and protein products together.

10. Add testable predictions

The manuscript would be stronger if it generated clear experimental predictions.

Suggested improvement: Add a section proposing tests such as:

• RNA primers supporting nonenzymatic replication of partially melted dsDNA

• stem-loop RNA replicating more efficiently than linear RNA

• CT-rich/AT-rich motifs guiding nonenzymatic transcription initiation

• A-rich sequences terminating nonenzymatic RNA extension

• stem-loop RNA undergoing reverse-transcription-like DNA synthesis

• two primitive tRNA-like molecules producing nonrandom hydrophobic/hydrophilic peptides

11. Improve citations and manuscript completeness

Some references use Wikipedia and missing access dates, and manuscript sections such as author contributions, funding, and acknowledgments are incomplete.

Suggested improvement: Replace Wikipedia references with scholarly sources where possible, add access dates where needed, and complete or remove blank manuscript sections.

Minor issues

1. Soften the title. Consider: “A Hypothesis for Nucleic Acid-Based Prebiotic Entities in the Origin of Life.”

2. Define “pre-life entity.” Clarify whether this means a molecule, molecular network, compartment, coacervate, or population of interacting nucleic acids.

3. Reduce teleological language. Replace terms like “seek,” “decide,” and “self-beneficial” with selection-based language.

4. Clarify reverse transcription chemistry. The proposed abiotic reverse transcription step is important but needs more chemical detail.

5. Discuss error rates and mutation. The model should explain how replication errors support evolution without destroying stored information.

6. Improve figure readability. Some labels are small; clearer legends and larger text would improve accessibility.

7. Add a limitations section. A concise limitations section listing the most speculative assumptions would improve transparency.

Overall assessment

This is a creative and ambitious hypothesis paper that attempts to explain the origin of life through DNA/RNA-based prebiotic entities capable of information storage, replication, product generation, and selection-like persistence. The strongest parts are the broad DNA/RNA interdependence model, the structured “problem-solving entity” framework, and the attempt to explain primitive translation through simplified wobble recognition.

However, the manuscript needs major conceptual strengthening. The author should more clearly separate facts from hypotheses, avoid over-anthropomorphic language, justify the prebiotic chemistry more rigorously, address compartmentalization, compare the model with existing origin-of-life theories, and add experimentally testable predictions. With these revisions, the manuscript could become a clearer and more useful conceptual contribution to origin-of-life research.

Competing interests

The author declares that they have no competing interests.

Use of Artificial Intelligence (AI)

The author declares that they used generative AI to come up with new ideas for their review.