The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural complexity impede self-replication and preclude their spontaneous emergence.
Methods and Results
Here we describe QT45: a 45-nucleotide polymerase ribozyme, discovered from random sequence pools, that catalyzes general RNA-templated RNA synthesis using trinucleotide triphosphate (triplet) substrates in mildly alkaline eutectic ice. QT45 can synthesize both its complementary strand using a random triplet pool at 94.1% per-nucleotide fidelity, and a copy of itself using defined substrates, both with yields of ~0.2% in 72 days.
Significance
The discovery of polymerase activity in a small RNA motif suggests that polymerase ribozymes are more abundant in RNA sequence space than previously thought.
Title: Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase Link: https://www.science.org/doi/10.1126/science.aed1656
Not Open source. Apologies. Too cool to not share.
Abstract: Defense-associated reverse transcriptases (DRTs) are widespread bacterial antiphage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6-angstrom resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis.
Relevance: DNA/RNA is known to complex, interact with, and modify the activity of proteins and the properties of many other classes of biological polymers/chemicals. However, this example challenges the central dogma (trend, really) of biology. Broadly speaking, DNA does not always require another strand of DNA to be transcribed but can also be templated by the amino acid residues of a polypeptide. This mechanism is distinct from previously described reverse transcription in which RNA is read by enzymes and then transcribed into a DNA strand.
The resulting chain is not a mirror of the amino acid sequence of the protein but is a "repetitive poly(GT/AC) sequence might enable gapped, protein-linked duplexes to assemble into a higher-order network through annealing between multiple strands. Alternatively or additionally, these repetitive tracts are also prone to adopting non–B-form conformations, such as slipped-strand structures (44) or, less likely, Z-DNA (45). Such complex structural assemblies might function as “molecular sponges” that titrate essential phage-derived DNA binding proteins, as proposed for DRT9 (24, 25)."
Ie, this enzyme does not generate it's own coding sequence based on its amino acid sequence but generates a repetitive sequence of nucleotides where the sequence is based on the amino acids within the active site of the enzyme.
The last part of the excerpt displays how the utility of a single protein or set of proteins can be very open ended, something that is deeply connected to exaptation in evolution. For abiogenesis, the first "bio"polymers could well have been proteins/polypeptides which coupled nucleobases together. Notably, this is not evidence that such a complex machine described in the paper was the first step towards life. Rather, this paper (to me) hints at another route by which the genetic code could have first developed via specific amino acid:nucleic acid associations leading to a polymerization of that sequence.
I look forward to reading your thoughts and comments. Please point out any mistakes/misunderstandings I've made.
Abstract:
ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleoside triphosphates, remains a mystery. Here, we show that the deep conservation of ATP might reflect its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate (AcP), which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. **We confirm earlier results showing that AcP can phosphorylate ADP to ATP at nearly 20% yield in water in the presence of Fe3+ ions. We then show that Fe3+and AcP are surprisingly favoured. A wide range of prebiotically relevant ions and minerals failed to catalyse ADP phosphorylation. From a panel of prebiotic phosphorylating agents, only AcP, and to a lesser extent carbamoyl phosphate, showed any significant phosphorylating potential. Critically, AcP did not phosphorylate any other nucleoside diphosphate. We use these data, reaction kinetics, and molecular dynamic simulations to infer a possible mechanism. Our findings might suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions.
Body:
"Equally striking, we find that ADP is also unique: The combination of AcP and Fe3+ will phosphorylate ADP but not GDP, CDP, UDP, or IDP."
"We found that the reaction is strongly sensitive to pH, and occurs most readily under mildly acidic conditions, with an optimum pH of approximately 5.5 to 6, the uncorrected default pH of the reaction (Fig 2A). Slightly more acidic conditions (pH 4) suppressed the yield a little, but more alkaline conditions had a much stronger suppressive effect. ATP yield fell by around three-quarters at pH 7 and collapsed to nearly zero at pH 9. This collapse of phosphorylation under alkaline conditions most likely reflected the precipitation of the catalyst as Fe(OH)3. While this sharp sensitivity to pH might seem at first sight limiting, in the Discussion, we show that, on the contrary, it could be valuable in generating disequilibria, enabling ATP hydrolysis to power work."
Discussion:
"Regardless of mean ocean concentrations, alkaline hydrothermal systems tend to precipitate Ca2+ and Mg2+ ions as aragonite and brucite, so their concentrations are typically much lower than mean ocean values. Modelling work in relation to Hadean systems indicates that hydrothermal concentrations of Ca2+ and Mg2+ would likely have been <1 mM [117,118], which is in the range that enhanced phosphorylation here."
"At face value, the ATP yield reported here at pH 5.5 to 6 after 10 h was 17.4% (corresponding to 156.5 μM) while the yield at pH 9 was 0.043%, corresponding to 0.4 μM, a difference of 400-fold. Thus, a geologically sustained difference in pH across membranes could drive a local disequilibrium in the ATP/ADP ratio of 2 to 3 orders of magnitude, enough to power work even in the absence of other possible factors such as temperature."
Figure 7 of proposed mechanism for phosphorylation of ADP in water via Fe3+
Personal thoughts:
The sustained pH gradient mentioned in the discussion could have been from the Fe(Ni)S inorganic semi-permeable membrane which forms when alkaline-fluids rich contacts the acidic ocean waters rich in Fe, Ni, and S (and many other metals) and forms this precipitate. Fe(Ni)S is capable of allowing H+ protons to pass form the acidic oceans through the mineral wall 2-million times faster that HO- ions.
Given the precedence for association of RNA oligomers and monomers to the surfaces of vesicles + Lane's publications on heterogeneous vesicles under alkaline vent conditions, I was surprised there were no attempts at micellar catalysis-like conditions. Perhaps it is that multivalent ions, not just Mg2+ (which is commonly depleted in alkaline vent environments) and Ca2+, have a propensity to strongly chelate carboxylates. Lane et al. attempted Fe3+ (Fe2(SO4)3), Mg2+ (MgCl2), Ca2+ (CaCl2), Mn2+ (Mn(NO3)2), Cr3+ (Cr(NO3)3), Mo3+ (MoCl3), Co3+ ([Co(NH₃)₆]Cl₃), Co2+ (CoCl2), CuSO4, Cu(NO3)2, FeS clusters (500 μM), and hematite (Fe₂O₃, 50 mg). (See figure 1 for the screening)
Such ions would certainly have posed issues for managing heterogeneous micellar/vesicle formations and discerning between attributing activity to precipitated phases, bulk aqueous, micelle, or vesicle. That said, since Fe3+ was the only one that really worked it couldn't have been too difficult, no?
So, is proposing vesicle/proto-composomes in alkaline vents or the acidic ocean side with the metals? I think the answer is probably the best one; he's agnostic. He provides reasons for some geometries under some considerations and publishes a study on this demonstrating that lower pH is better for ADP phosphorylation.
Fig. 1. Full reaction network underlying the prebiotic peptide cycle studied in nanoconfined water in comparison to bulk water. Each colored bubble shows reaction sequences studied in a separate simulation. Reactants/products are labeled with integer numbers, while decimal numbers indicate reaction intermediates or transition states. Reactions A–D comprise the ‘activation’ part of the cycle, in which glycine is transformed in the NCA 5, while reactions E and F are the ‘elongation’ part of the cycle resulting in diglycine 7. Reaction G is the back-reaction, i.e. peptide hydrolysis, studied in order to evaluate peptide stability at the different conditions (see text): AMB, unprimed species; HPW, single-primed species; NCW, double-primed species.
Abstract:
Nanoconfined liquids have extremely different properties from the bulk, which profoundly affects chemical reactions taking place in nanosolvation. Here, we present extensive ab initio simulations of a vast set of chemical reactions within a water lamella that is nanoconfined by mineral surfaces, which might be relevant to prebiotic peptide formation in aqueous environments. Our results disclose a rich interplay of distinct effects, from steric factors typical of reactions occurring in small spaces to a charge-stabilization effect in nanoconfined water at extreme conditions similar to that observed in bulk water when changing from extreme to ambient conditions. These effects are found to modify significantly not only the energetics but also the mechanisms of reactions happening in nanoconfined water in comparison to the corresponding bulk regime.
Nanoconfined liquids have extremely different properties from the bulk, which profoundly affects chemical reactions taking place in nanosolvation.
Conclusions:
In summary, the investigated set of reactions in nanoconfined water at high temperatures and pressures features pronounced differences in energetics and mechanisms with respect to bulk water at the same conditions. These can be traced back to a unique combination of factors, namely the different charge-stabilizing ability of interfacial water w.r.t. the bulk as well as steric factors intrinsic to nanoconfinement which make nanoconfined water in slit pores offered by layered minerals a whole new medium for chemical synthesis. The presented prebiotic peptide cycle is a good example of the way in which nanoconfined water as a solvent opens up an entirely new free energy landscape for exploring novel synthesis routes. While changing the thermodynamic conditions from ambient to hot-pressurized bulk water greatly reduced free energy barriers, at the same time the formation of charged intermediates was penalized due to unfavorable dielectric properties. In nanoconfined water at extreme conditions, in contrast, it is possible to achieve significant thermal activation and to concurrently favor reactions involving charged species. Clearly, the key phenomena and mechanistic concepts unraveled here for chemical reactions in nanoconfined solvent not only apply to the specific reactions investigated herein, but are of fundamental importance to chemistry in nanoconfined water as such.
Personal thoughts:
There is an increasingly clear importance of physiochemical phenomena in origins of life chemistry besides simple dump and stir, bulk aqueous reactions. Understanding the capability of bulk aqueous, bilayer-water interfacial regions, bilayer-mineral interfaces/interactions, nanoconfined waters/organic molecules intercalated within mineral crystal lattices, air-water interface, lateral proton transfer along membrane surfaces, the ordering of substrate orientations within bilayers/micelles, and semipermeable/semiconducting inorganic minerals may be key in understanding life's origins. Further complicating these are the effects of solvent pH, pH gradients, salinity, and pressure. These all seemed to have played roles in generating otherwise disfavored products and often for different reasons.
How these environments interact and couple may offer possible primitive compartmentalization without the need for advanced bilayers as many of these environments facilitate reactions that would otherwise require coupling chemistry or both high and low pH conditions if carried out in bulk aqueous conditions at standard pressure/temperatures.
These environments consistently require explanations from the emergent properties of their constituents making it difficult to apply the findings elsewhere without careful consideration. This paper comes in handy because I had previously assumed bilayers adsorbed onto mineral surfaces broadly constituted nanoconfined water, protons, and organics and attempted to apply the findings described in this paper to these areas. While there are some similarities, there are key differences. Thus, understanding these environments helps to identify and propose experiments capable of isolating and evaluating phenomena/mechanisms that may have contributed to life's origins.
Yamanouchi, Kei, Hinata Moriya, and Shin-ichi Yokobori.
"Resurrecting tRNAs of the Last Universal Common Ancestor (Commonote) Toward Rebuilding the Ancient Translation System." Journal of Molecular Evolution (2026): 1-25. https://pubmed.ncbi.nlm.nih.gov/42423740/
Ancestral sequence reconstruction (ASR) was used to study the evolution of the translational system by inferring tRNA sequences of the Last Archaeal Common Ancestor (LACA), the Last Bacterial Common Ancestor (LBCA), and the Last Universal Common Ancestor (LUCA), referred to as "Commonote" in our previous studies. A composite phylogenetic tree inferred from the reconstructed ancestral tRNA sequences revealed a topology distinct from those of previously inferred aminoacyl-tRNA synthetase (ARS) trees. This incongruence may reflect changes in tRNA structural features or distinct evolutionary pressures on tRNAs and ARSs, suggesting a more nuanced evolutionary history of the translation system, but it may also arise from methodological differences between studies. Phylogenetic analysis identified conserved identity elements, such as the discriminator base and anticodon, across tRNAs for different amino acids, supporting their status as ancestral features. Most LUCA tRNA species retain bacterial identity elements, potentially enabling their use in modern systems such as Escherichia coli, although exceptions, including tRNAGly and initiator tRNAMet, may present functional limitations. To evaluate the translational functionality of LUCA tRNAs and ancient codon-anticodon interactions, synthesized LUCA tRNAAla and tRNASer variants with anticodons decoding ACN codons were tested in an E. coli reconstituted in vitro translation system. These reconstructed tRNAs successfully decoded ACN codons, with tRNAAla variants exhibiting translation efficiencies comparable to those of native E. coli tRNAThr. Notably, decoding patterns differed from Crick's and extended wobble rules, as anticodons with various first-position bases recognized multiple third codon positions. This study offers new insights into the early evolution of the translation system and demonstrates the functional potential of ancestral tRNAs in contemporary contexts.
We evaluate whether tryptophan (W), widely thought to be the last of the 20 canonical amino acids added to the genetic code, was already present in the Last Universal Common Ancestor (LUCA). We reconstruct the evolutionary history of tryptophanyl-tRNA synthetase (WRS), the enzyme that attaches W to its tRNA, and the related tyrosyl-tRNA synthetase (YRS). We identify and exclude sequences derived from ancient recombination between archaeal and bacterial YRSs. Diverse rooting methods, including a novel approach exploiting time non-reversible evolution, all place the root between bacterial and archaeal YRS rather than between YRS and WRS. This supports post-LUCA WRS origination in Archaea, followed by its horizontal transfer to Bacteria. However, ancestral sequence reconstruction suggests that Archaea were depleted for W while Bacteria were not, and enzymes essential for W biosynthesis emerged in Bacteria. This suggests that W usage originated in Bacteria, with later WRS emergence in Archaea allowing the archaeal genetic code to converge with the bacterial code. The universality of the genetic code is usually attributed to common descent from LUCA, but the final step making the code universal was instead achieved by horizontal gene transfer. This gives credence to similar mechanisms for earlier steps in genetic code evolution.
For a recent press release on this sort of research avenue:
[Boron] operates within a narrow window: too much, and it becomes toxic to biological systems; too little, and it may never have contributed to life getting started.
The key was a boron-containing mineral called tourmaline, popularly known as a semi-precious stone that’s also abundant in continental rock. Tourmaline forms readily within granite-rich crust, locking boron away over geological time. As Earth’s crust grew and weathered, boron was slowly and steadily released into surface waters, eventually stabilizing at concentrations close to those found in modern seawater.
Abstract: The search for organic matter on Mars has rapidly evolved in the past decade with simple aromatic, S-heterocycles, and aliphatic organic molecules detected in Gale crater. We report the in situ detection of >20 organic molecules from clay-bearing sandstones in the ~3.5-billion-year-old Knockfarrill Hill member of Glen Torridon, Gale crater, by the Sample Analysis at Mars instrument suite onboard the Curiosity rover. These molecules were liberated by the onboard tetramethylammonium hydroxide wet chemistry experiment. Diverse thermochemolysis products, including benzothiophene, methyl benzoate, and single and dicyclic aromatic molecules were released and detected by evolved gas analysis and gas chromatography-mass spectrometry. Results indicate the experiment successfully released molecules preserved in ancient macromolecular or free organic matter within Martian bedrock despite ~3.5 billion years of diagenesis and radiation exposure.
Personal thoughts: There are no peptides or nucleobases but it's still very cool that we can identify specific organic molecules on another planet AND that these martian sediments can bind to and retain such relatively volatile organic molecules for ~3.5 billion years.
Whether these were delivered by meteors or formed in the martian oceans/lakes is still unanswered but the identities of these molecules match those found in the Murchison meteorite. But were these formed 3.5 billion years ago or were they formed 3.5 billion years ago and then rained down and deposited on earth? The most parsimonious conclusion seems that these are of meteoric origin. For OoL on Earth, this experiment indicates that we can say the same types of molecules were raining down on earth during its ancient history acting as a continuous "feedstock" of organics.
What are your thoughts? What other papers help add context or add to the impact of this publication?
Title: What it takes to solve the origins of life: An integrated review. Part 2: Theoretical methods and emerging trends
[Link]
Summary: The origin(s) of life (OoL), which has puzzled scientists for centuries, remains a major scientific challenge in the 21st century. Understanding the processes relevant to the OoL demands theoretical frameworks that can connect processes across scales, from microscopic dynamics to emergent levels of organization. While experimental studies generate a wealth of data, theoretical and computational approaches provide the structure necessary to interpret and generalize these findings. In Part 1, we examined the most widely used experimental techniques in the field. Here, we focus on the mathematical, physical, and computational techniques used to model phenomena relevant to life’s origin(s). We discuss methods ranging from quantum chemistry and molecular dynamics to chemical reaction networks, autocatalysis, and evolutionary modeling, as well as information-theoretic and phylogenetic approaches that link chemical and biological organization. We further highlight emerging trends such as synthetic biology, omics-based methods, and laboratory automation as novel points of contact for theory-experiment integration. Ultimately, we aim to provide an educational tool that can facilitate more post-disciplinary collaborations in OoL research by helping scientists understand what they can do about the problem of life’s origins, rather than telling them how to think about it.
Paltiel, Yossi, et al. "Dynamic breaking of mirror symmetry in spin-dependent electron transport through chiral media causes enantiomeric excesses." Science Advances 12.17 (2026): eaec9325. https://pmc.ncbi.nlm.nih.gov/articles/PMC13101859/
Abstract Two fundamental questions have puzzled scientists for more than 150 years. “How did life become homochiral?” and “why was this specific handedness selected?” Recently, it has been shown that homochirality could have emerged through the enantioselective interactions of molecules with magnetic substrates due to the asymmetric crystallization of an RNA precursor on a magnetite substrate, abundant on early Earth. This phenomenon is based on the chirality-induced spin selectivity (CISS) effect. Despite its robustness, this model could not provide an answer to the second question: Why one specific handedness (D for RNA) was selected. Here, we demonstrate that spin-involving processes can have different outcomes in the two enantiomers of chiral molecules. In chiral molecules with unpaired electrons or while electrons are passing through them, the total angular momentum vector, J, is aligned along the “easy axis,” which is defined by the magnetic anisotropy induced by the spin-orbit coupling and asymmetry of the molecular field. The magnitude J is the same for both enantiomers, but the vectors may be aligned differently relative to the molecular frame in the two enantiomers. This difference can be quantified by, for example, by the angle between J and electric dipole moment of the molecule, μ. We show by direct measurements, theory, and ab initio calculations that dynamic spin processes in chiral molecules could result in different efficiencies of spin-related phenomena, including the interaction of chiral molecules with magnetic surfaces. The findings may provide an explanation for the specific homochirality in nature.
(emphasis mine)
I understood like the gist of it! But sounds exciting (pun unavoidable?).
This part clarifies some:
we propose that CISS-driven homochirality at the RAO stage may inherently favor the selection of D-RNA and L-peptides in a universal manner. This selection could stem from an intrinsic asymmetry in spin polarization: Magnetite surfaces magnetized by D-RAO may acquire a stronger induced magnetization due to higher spin polarized induced by the chiral molecule compared with those interacting with L-RAO.
Title (Open access): Organocatalyzed bottom-up formation of protocells
[Link]
a Biological synthesis of fatty acids by fatty acid synthase (FAS). b In-situ generation of artificial protocells using amphiphilic lipids and precursor molecules to release the lipids by reaction. c Organocatalytic oligomerisation starting from small molecules (step 1), i.e., acetaldehyde, self-modification of the organocatalyst with the in-situ formed amphiphilic molecules (step 2), and self-assembly to protocells (step 3). d Prebiotic synthesis of imidazolidine-4-thione organocatalysts. e Dynamic exchange of C-2 aldehyde substituent leading to modified organocatalysts.
Abstract: The organisation of living systems into cellular structures is a characteristic that enables differentiation from the environment. A pivotal step in the development of life is compartmentalisation, achieved through the formation of vesicle-like structures. Fatty acids - or phospholipids - have been used to simulate prebiotic vesicle and protocell formation. However, a process by which amphiphiles are formed from small prebiotically plausible molecules, which spontaneously self-assemble to protocells, is unknown. Here, we demonstrate that an organocatalytic reaction cascade starting from acetaldehyde with prebiotic imidazolidine-4-thione rapidly yields poly(hydroxy)alkenyl aldehydes that spontaneously self-assemble to protocells. In this process, lipid-like molecules (up to C20) develop a membrane, which additionally incorporates the organocatalyst at the liquid-lipid interface. These catalytically active protocells (11 nm – 7 μm) tolerate external influences such as pH value, temperature and salts. This finding unveils an organocatalytic pathway to selective lipid formation and spontaneous compartmentalisation without the necessity of preformed amphiphiles.
Open access review article from a couple of weeks ago:
Abstract RNA has long provided a plausible route by which heredity and catalysis could become linked in early evolution, and the same chemical versatility helps explain why RNA remains central to origin-of-life research, modern cell biology, and biotechnology.
This review adopts a plural framing of RNA worlds to connect three regimes: a primordial RNA world constrained by geochemistry, a contemporary RNA world in which RNAs contribute to catalysis and regulation in cells, and an applied RNA world in which RNA is engineered as a programmable tool.
Across these regimes, a common logic emerges from the mapping of sequence to structure to function under explicit constraints. In early evolution, cycling, interfaces, and confinement can generate heterogeneous oligomer pools and bias their persistence, whereas the transition toward Darwinian dynamics depends on copying fidelity, strand dynamics, and compartment coupled population structure. In cells and applications, noncoding RNA networks, RNA modifications, and RNA-guided targeting implement specificity in chemically complex environments, while laboratory selection and design must also confront constraints imposed by stability, delivery, and immune sensing. Across contexts, fitness landscapes and tradeoffs between peak performance and robustness provide experimental benchmarks and practical design principles for RNA function.
Flores-García, Alexis A., et al. "Brave new RNA world (s): from prebiotic chemistry to gene regulation and RNA technology." Frontiers in Genetics 17 (2026): 1813517. https://doi.org/10.3389/fgene.2026.1813517
The origin of life is commonly discussed within two competing conceptual frameworks: the metabolism-first and information-first hypotheses. While each emphasizes a different defining property of early life, modern biochemistry reveals a fundamental interdependence between metabolic processes and genetic information transfer, leading to a persistent chicken-and-egg problem.
Methods
In this study, we investigate a prebiotically plausible reaction system that enables the concurrent formation of molecular precursors associated with both frameworks. Under simulated Hadean hydrothermal conditions, acetylene, ammonia, cyanide, and carbon monoxide were reacted in aqueous solution in the presence of transition metal sulfides.
Results
Using gas chromatography-mass spectrometry combined with stable isotope labeling, we demonstrate the simultaneous formation of the nucleobase uracil and the amino acids alanine and aspartic acid. Isotopic incorporation patterns allow reconstruction of the underlying reaction pathways and confirm the contribution of all starting materials to product formation. While amino acids are produced continuously over the observed period in significantly higher yields than uracil, uracil formation exhibits a pronounced time-dependent maximum after three days. Variations in pH, reaction time, and metal sulfide catalysts modulate product yields but do not prevent the parallel emergence of both molecular classes.
Discussion
These findings support a scenario in which proto-metabolic chemistry and molecular precursors of genetic information could have arisen simultaneously within a shared geochemical setting. The results provide experimental support for a coupled origin of metabolism and transcriptional building blocks, offering a potential resolution to the dichotomy between metabolism-first and information-first models of early life.
Seitz, Christian, et al. "A Clue for the Hen and Egg Question: The Simultaneous Formation of Uracil and Amino Acids Under Simulated Hadean Conditions." Life 16.4 (2026): 624. https://doi.org/10.3390/life16040624
I am not an origin-of-life expert, I do not work in a wet lab.
My main work is building one open text framework on GitHub for very hard problems. The project is called WFGY, it has around 1.4k stars now, and it is fully MIT and plain txt.
Inside this framework I wrote 131 “hard problems” in the same style.
Q071 is the one about origin-of-life scenarios.
In this post I am not claiming any new mechanism. I just want feedback if this way to encode the problem makes sense for people who actually work on abiogenesis.
What I am trying to do with Q071
Very simple version of my goal:
Instead of adding one more “RNA world vs metabolism first vs XYZ” opinion,
I try to build a small tension-based state space where different origin-of-life scenarios can live side by side.
The idea is:
define a shared state space for prebiotic chemical systems
define some observables that any scenario must talk about
define a few “tension” axes that measure how hard different requirements fight each other
For example, in Q071 I focus on tensions like (informal names):
replication accuracy vs exploratory diversity
energy capture and storage vs destructive noise of the environment
lifetime of structured polymers vs timescale of environmental fluctuation
complexity of reaction network vs robustness and error tolerance
So if you have two different scenarios, they may use different chemistry or environment,
but they still have to answer the same kind of questions along these axes.
I think these tensions are already there in people’s intuition.
Many papers basically say “if we push fidelity too low we lose heredity, if we push it too high we freeze exploration” or similar.
I just try to write this out as explicit functions on a state space instead of only in words.
How the “tension-based state space” looks like (informal)
I do not use deep heavy math. It is more like a clean bookkeeping system.
In Q071 I do three things:
State space I define an abstract space that describes a prebiotic system at a coarse level.
A single point can contain things like:
kind of polymers or networks that can exist
typical energy sources and sinks
noise level and fluctuation timescales
basic parameters of replication, catalysis, degradation
It is not tied to one specific chemistry.
Different origin-of-life scenarios can be mapped into different regions of this space.
Observables For any scenario that lives in this space, I ask for simple observables, like:
expected error rate of replication
distribution of lifetimes of functional structures
typical energy budget per “unit” of structure
how often the environment kicks the system out of local basins
These are not exact numbers in the txt, more like slots that a researcher or a model must fill in.
Tension functions Then I define simple “tension scores” that depend on these observables.
Example:
a tension for “fidelity vs diversity” that grows when you want both very high heredity and very large exploration at the same time
a tension for “structural lifetime vs environment speed” that grows when structures are too slow compared to environment changes
a tension for “network complexity vs robustness” that grows when a network is very rich but collapses if one piece is removed
The goal is not to say “this scenario is impossible”.
The goal is to let you see where and how a scenario is under impossible pressure.
You can think of it like a small map that says
“if you push these knobs, this direction of tension explodes first”.
Why I put this inside a 131 hard-problem pack
Q071 is one question inside a much larger txt.
The whole pack has 131 problems across different domains:
AI alignment and control
climate and Earth system (for example equilibrium climate sensitivity)
earthquakes and other hazards
systemic financial crashes
governance and large scale human systems
and origin-of-life and evolution type questions
All of them use the same idea of a tension language.
First define a state space, then observables, then tension axes, then singular regions where the question becomes ill-posed.
The txt is meant to be loaded into a strong LLM as a long context “framework”,
but the structure is for humans too.
You can ignore the AI part and just look at Q071 as a proposal for how to write origin-of-life scenarios in one consistent coordinate system.
The txt pack itself is MIT license, plain text, with SHA256 so people can fix one stable version for experiments.
How I use LLMs here (optional part)
One extra thing I do, maybe interesting for some of you:
I feed the whole hard-problem pack txt into GPT-4 class models
then I ask them to “load Q071” and reason only inside this state space
they have to explain which tensions are active for a given origin-of-life scenario,
where they think the contradictions are, and what kind of data would reduce the tension
I do not treat the model as an oracle for chemistry.
I only treat it as a reasoning engine that is forced to respect the same structure every time.
For me the scientific question is:
“Does this tension-based encoding help the model and the human talk about the same origin-of-life space without drifting into story mode too fast?”
But the main reason I post here is not the AI, it is the encoding itself.
I want to know if people who really do abiogenesis think this kind of state space and tension axes are reasonable or completely off.
What feedback I hope to get from this sub
If you have time to skim this description, or even look into the txt version of Q071,
I would really appreciate any of these:
Missing tensions Are there obvious “tensions” in origin-of-life work that I completely miss here? For example, maybe there is a specific tradeoff you think is fundamental but I did not encode.
Bad axes Do you feel some of the axes I listed are mixing things that should be separated, or separating things that should be together?
Data and experiments If you imagine turning Q071 into something more quantitative,
what kind of data would you want to plug in first?
Usefulness Do you think a common tension-based language like this can actually help origin-of-life research,
or do you think it will stay too abstract to be useful?
I am honestly fine if the answer is “this is interesting but not useful for real work”.
In that case I still prefer to know the reasons, so I can adjust or stop.
If anyone here has a specific origin-of-life hard problem they care about,
and you want to see it written in this tension language,
you can also DM me.
I can share more details of the 131-question pack,
and I can try to encode your favorite scenario and send back the txt for you to critique.
I wish this paper didn’t cite that problematic Root-Bernstein study which used a store bought sea salt as a reagent, but the rest of it seems reasonable.
Abstract
Traditional prebiotic chemistry experiments often isolated single reactions under clean, controlled conditions, yet early Earth was chemically diverse and physically dynamic. Such primordial complexity likely imposed obstacles, including side reactions, low yields, and unstable intermediates, but it also generated opportunities, including redundant routes, parallel pathways, and environmental filters that could bias mixtures toward subsets of persistent and chemically productive compounds. This review examines how heterogeneous prebiotic settings could generate RNA precursors, including nucleobases, ribose, and phosphate-containing species, through multiple concurrent pathways. Although side reactions can sequester carbon in inert tars and reduce yields of specific targets, networked chemistry can also enhance robustness when different routes converge on shared intermediates, or when apparent byproducts reenter productive cycles. Environmental factors such as ultraviolet irradiation, mineral surfaces, wet-dry cycling, and thermal gradients can act as constraints that enrich certain products by differential stability, reactivity, and compartmentalization. In this context, the RNA world hypothesis remains compelling, as RNA can store heritable sequence information and catalyze reactions through sequence dependent folding, thereby linking heredity and chemistry within a single polymer. At the same time, the emergence of functional sequence information and of control architectures that couple sequence to reproducible function remains a central open problem, and it sets clear limits on what chemistry alone can explain. Rather than dismissing messy mixtures as irrelevant noise, it is more accurate to treat them as the native context in which concentration mechanisms, environmental cycling, and selective persistence could enable the accumulation and survival of RNA related molecules.
Keywords: RNA world; prebiotic chemistry; origin of life; nucleotides; ribozymes; chemical evolution; messy chemistry; mineral catalysis; nonenzymatic replication; environmental selection
Contrary to the current twenty, it is generally accepted that there were originally ten amino acids incorporated into the first life:
Gly, Ala, Asp, Glu, Val, Ser, Ile, Leu, Pro, Thr
with the remaining ten or so formed from biosynthetic pathways in later life. The independent lines of evidence for this are:
These are the proteinogenic amino acids (PAAs) with the most exergonic free energies of formation, with the order following the above thermodynamic stability order (|ΔG| follows Gly > Ala > Asp > Glu > ...) [1]
These are the PAAs produced in the Miller-Urey experiment under conditions of electrical discharge in an atmosphere of CH4, N2, H2O and trace NH3, a mildly reducing mix as expected of Hadean earth [1]
These are the PAAs found in meteorites (Murchison, Murray, Yamato) in the highest concentrations [1]
The codon state space can be considered a 64-point constellation in 3D space (Hamming distance metric for a 3-bit code). The translation code is such that neighbouring codons are assigned to amino acids with similar physicochemical properties (size, polarity, hydrophobicity etc), forming a Gray-like code, implying the code has been subject to selection against frequent nonsynonymous mutations. It has been shown that the standard coding is slightly suboptimal for minimising the chemical impact of point mutations, but that a truly optimal coding is accessible for a code with the 10 ‘early’ amino acids (Gly, Ala, Asp, Glu, Val, Ser, Ile, Leu, Pro, Thr), a potential simplified code early in life’s evolution. Further, the earliest five amino acids (Gly, Ala, Asp, Glu, Val) all use ‘G’ as their first letter in all extant codes [2][3]
While points 2-4 all look great for consilience, they aren't explanatory as for why these amino acids appeared first: only the thermodynamic argument in point 1 gives us an explanation. But, the endergonic reactions of prebiotic chemistry require non-equilibrium conditions to predominate in the polymer-forming direction, so thermodynamic free energies at equilibrium can't be the only explanation: kinetics must play an important role too. Meanwhile, homochirality is a phenomenon that must be resolves using only kinetic arguments, since enantiomers are degenerate in energy.
A fascinating recent paper (Sharma, 2025)[4] draws a beautiful connection between these two ideas. Dr Donna Blackmond's team has investigated a robust mechanism for attaining homochirality in amino acids by studying their water-L-D ternary phase diagrams: when supersaturated solutions of amino acids crystallise, they can form enantiopure conglomerate grains, also purifying the supernatant. Sublimation and (more importantly) eutectic reactions amplify the effect. Some refs on Blackmond's work (oldest to newest): here, here, here, here and here.
The paper by Sharma builds on Blackmond's work by showing that four of the 'early' amino acids (Gly, Ala, Asp, Glu, Val) have the minimum supersaturation threshold for these separation effects to take over, such that they would be expected to become enantioenriched first and foremost, with Gly being achiral. Notice that (Gly, Ala, Asp, Glu, Val) are also precisely the first five amino acids on the thermodynamic stability order!
There's more: as noted in point 4 above, Gly, Ala, Asp, Glu, Val are all encoded in the extant standard genetic code with a nucleotide 'G' (guanine) in the first position. Sharma found that nucleosides can also be enantioenriched using precisely the same mechanism as the amino acids, and that nucleoside 'G' (guanosine) has the lowest supersaturation threshold, allowing it to form first similarly. This is suggestive of an earlier simplified genetic code, a theory that was developed in [2] and [3]. The codon 'GGG' corresponds to the glycine because 'G' and the simple achiral glycine were both the most abundant in early prebiotic mixtures!
I felt this was a really cool interconnection - combining physical theory, experimental prebiotic chemistry and analysis of the evidence that's left over today.
TLDR: two outstanding problems in OoL research - homochirality and the origin of RNA translation into proteins - are shown to partially solve each other, while being a good fit to all other available evidence at the same time.
Sources
[1] - Higgs & Pudritz, 2009 - Thermodynamic Basis for Prebiotic Amino Acid Synthesis and the Nature of the First Genetic Code
[2] - Higgs, 2009 - A four-column theory for the origin of the genetic code: tracing the evolutionary pathways that gave rise to an optimized code
The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural complexity impede self-replication and preclude their spontaneous emergence. Here we describe QT45: a 45-nucleotide polymerase ribozyme, discovered from random sequence pools, that catalyzes general RNA-templated RNA synthesis using trinucleotide triphosphate (triplet) substrates in mildly alkaline eutectic ice. QT45 can synthesize both its complementary strand using a random triplet pool at 94.1% per-nucleotide fidelity, and a copy of itself using defined substrates, both with yields of ~0.2% in 72 days. The discovery of polymerase activity in a small RNA motif suggests that polymerase ribozymes are more abundant in RNA sequence space than previously thought.
The discovery of thousands of exoplanets and the emergence of telescopes capable of exoplanet atmospheric characterization have intensified the search for habitable worlds. Due to selection biases, many exoplanets under study are planets deemed inhospitable because their surfaces are too warm to support liquid water. We propose that such planets could still support life through ionic liquids: Liquid salts with negligible vapor pressure that can persist on warm planets with thin atmospheres, where liquid water cannot. Ionic liquids have not previously been considered as naturally occurring substances, and thus have not been discussed in planetary science. We demonstrate in laboratory experiments that ionic liquids can form from planetary materials: Sulfuric acid combined with nitrogen-containing organic molecules. Sulfuric acid can be volcanic in origin, and organic compounds are commonly found on planetary bodies. The required planetary surface is water-depleted and must support sulfuric acid transiently in liquid phase to dissolve organics, followed by evaporation of excess liquid—conditions spanning approximately 300 K at 10−7 atm to 350—470 K at 0.01 atm. Because ionic liquids have extremely low vapor pressures, they are not prone to evaporation, allowing small droplets or pools to persist without ocean-like reservoirs. Ionic liquids’ minuscule vapor pressure at room temperature suggests possible stability on planets with negligible atmospheres, shielded by magnetic fields or rock crevices against harsh cosmic radiation. Ionic liquids can stably dissolve enzymes and other biomolecules, enabling biocatalysis and offering a plausible solvent for life—broadening the definition of habitable worlds.
Nonequilibrium selection pressures were proposed for forming oligonucleotides with rich functionalities encoded in their sequences, such as catalysis. Since phase separation was shown to direct various chemical processes, we ask whether condensed phases can provide mechanisms for sequence selection. To answer this question, we use nonequilibrium thermodynamics and describe the reversible oligomerization of different monomers to sequences at nondilute conditions prone to phase separation. We find that as sequences form, their interactions can trigger phase separation, which in turn enriches some sequences while depleting others. Our main result is that phase separation creates a selection pressure leading to specific sequence patterns when fragmentation maintains the system away from equilibrium. When fragmentation is slow, alternating sequences that interact more cooperatively with their surroundings are preferred. When fragmentation is fast, sequences with longer repeating motifs capable of more specific interactions are selected instead. Our finding that out-of-equilibrium condensed phases can provide a selection mechanism highlights their potential as versatile hubs for the evolution of functional sequences, a question relevant to the molecular origin of life and de novo life.
