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Life
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Chemical Evolutionary Pathways to Origins of Life
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Chemical Evolutionary Pathways to Origins of Life

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Origin of Life".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 2279

Special Issue Editors

Dr. Claudia Huber

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Guest Editor
Lehrstuhl für Strukturelle Membranbiochemie, Fakultät Chemie, Technische Universität München, Lichtenbergstr. 4, 85748 Garching, Germany
Interests: origin of life; transition metal sulfides; catalysis; hydrothermal conditions; acetylene; carbon fixation; chemical evolution; early metabolism
Special Issues, Collections and Topics in MDPI journals
Dr. Christian Seitz

E-Mail Website
Guest Editor
Structural Membrane Biochemistry, Technical University of Munich, Lichtenbergstr. 4, 85748 Garching, Germany
Interests: origin of life; early metabolism; surface catalysis; isotopologue profiling

Special Issue Information

Dear Colleagues,

The question of how life originated on Earth has fascinated humanity for centuries and is therefore a topic of great interest. The answer to this question involves researchers from different fields, like physics, astronomy, chemistry, biochemistry and biology, and the approaches to solving the problem are widespread. Even within the evolutionary approach of the formation of biomolecules and life on Earth, there is a multitude of theories about how this could happen, quite apart from whether the formation actually took place on Earth, or if the first biomolecules had an extraterrestrial origin. These theories include the well-known metabolism-first and RNA world hypotheses. Also, it has been suggested that proteins or lipids built the first self-sustaining entities. Concerning the location of life’s evolution, there are also discussions on where to look: deep sea, shallow ponds, volcanic sites, hot or cold conditions, alkaline or acidic conditions, and so on. From a chemical point of view, inorganic precursors like CO2, CO, acetylene, ammonia, sulfides, and so on, would react in the first steps to becoming simple biomolecules like acetic acid, pyruvate, succinic acid, amino acids, fatty acids and amides, just to name a few. These starter reactions are followed by a metabolism-like reaction network, leading to more sophisticated biomolecules like peptides. In combination with the synthesis of lipid membranes, this may have led to a so-called pioneer organism. In combination with protein and enzyme formation, the genetic machinery of LUCA (last universal common ancestor) could have evolved. In this Special Issue, all possibilities for a chemical evolution of life should be further examined and highlighted.

Dr. Claudia Huber
Dr. Christian Seitz
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • origin of life
  • metabolism-first
  • early Earth
  • iron–sulfur world
  • chemical evolution 
  • cellularization
  • surface catalysis
  • pioneer organism

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Published Papers (3 papers)

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13 pages, 1115 KB  
Article
A Clue for the Hen and Egg Question: The Simultaneous Formation of Uracil and Amino Acids Under Simulated Hadean Conditions
by Christian Seitz, Denis Schuldeis, Konstantin Vogel, Wolfgang Eisenreich and Claudia Huber
Life 2026, 16(4), 624; https://doi.org/10.3390/life16040624 - 8 Apr 2026
Viewed by 1125
Abstract
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 [...] Read more.
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. 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. 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. 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. Full article
(This article belongs to the Special Issue Chemical Evolutionary Pathways to Origins of Life)
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17 pages, 2966 KB  
Article
The Formose Reaction with SO2: A Computational Study
by Emily M. Sisson and Jeremy Kua
Life 2026, 16(3), 513; https://doi.org/10.3390/life16030513 - 20 Mar 2026
Viewed by 698
Abstract
This study examines the influence of SO2 and its hydrate H2SO3 on the free energies of the core autocatalytic cycle of the formose reaction. We find that SO2 and H2SO3 readily condense with aldehyde and [...] Read more.
This study examines the influence of SO2 and its hydrate H2SO3 on the free energies of the core autocatalytic cycle of the formose reaction. We find that SO2 and H2SO3 readily condense with aldehyde and alcohol functional groups to form bisulfite analogs of formose proto-metabolites under modeled conditions. The bisulfite functional group can provide intramolecular catalytic enhancement in specific isomers towards aldol additions and the retroaldol step that regenerates two equivalents of glycolaldehyde from tetrose. The bisulfite moiety reduces the favorability of the parasitic Cannizzaro side-reaction both thermodynamically and kinetically, thus potentially furnishing more throughput towards forming sugars. As a prebiotic analog to phosphate, we find that bisulfite slightly stabilizes ribose over its C5 aldose diastereomers thermodynamically, although the effect is modest and may be influenced by solution dynamics. Full article
(This article belongs to the Special Issue Chemical Evolutionary Pathways to Origins of Life)
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Other

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7 pages, 425 KB  
Opinion
The RNA-First Fallacy: Conflating Evolutionary Ancestry with Prebiotic Primacy
by Amit Kahana
Life 2026, 16(5), 837; https://doi.org/10.3390/life16050837 (registering DOI) - 19 May 2026
Abstract
The RNA-World hypothesis remains the most widely accepted framework in origins-of-life research, anchored in compelling biochemical evidence for RNA’s deep evolutionary ancestry. However, this viewpoint routinely extends beyond that and is frequently conflated with claims that RNA served as life’s primal substrate. This [...] Read more.
The RNA-World hypothesis remains the most widely accepted framework in origins-of-life research, anchored in compelling biochemical evidence for RNA’s deep evolutionary ancestry. However, this viewpoint routinely extends beyond that and is frequently conflated with claims that RNA served as life’s primal substrate. This essay argues that the RNA-First paradigm, in its pursuit of this claim, systematically projects biological biases onto a chaotic and combinatorially vast abiotic landscape. It relies on privileged, highly complex molecular constructs whose spontaneous emergence in such combinatorial settings is overwhelmingly implausible. Critically, the experimental evidence accumulated in support of RNA-First has largely demonstrated the compatibility of RNA with prebiotic conditions, but not its probability, necessity, or chemical precedence over the numerous alternatives that abiotic chemistry affords. The eventual emergence of RNA chemistry demands a preceding protobiological stage, characterized by chemically diverse, collectively autocatalytic molecular networks. Embracing this broader protobiological framework, and confronting the true combinatorial complexity of abiotic chemistry, is essential for a rigorous and unbiased account of life’s origin. Full article
(This article belongs to the Special Issue Chemical Evolutionary Pathways to Origins of Life)
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