Genetics first or metabolism first? The formamide clue
Abstract
Life is made of the intimate interaction of metabolism and genetics, both built around the chemistry of the most common elements of the Universe (hydrogen, oxygen, nitrogen, and carbon). The transmissible interaction of metabolic and genetic cycles results in the hypercycles of organization and de-organization of chemical information, of living and non-living. The origin-of-life quest has long been split into several attitudes exemplified by the aphorisms "genetics-first" or "metabolism-first". Recently, the opposition between these approaches has been solved by more unitary theoretical and experimental frames taking into account energetic, evolutionary, proto-metabolic and environmental aspects. Nevertheless, a unitary and simple chemical frame is still needed that could afford both the precursors of the synthetic pathways eventually leading to RNA and to the key components of the central metabolic cycles, possibly connected with the synthesis of fatty acids. In order to approach the problem of the origin of life it is therefore reasonable to start from the assumption that both metabolism and genetics had a common origin, shared a common chemical frame, and were embedded under physical-chemical conditions favourable for the onset of both. The singleness of such a prebiotically productive chemical process would partake of Darwinian advantages over more complex fragmentary chemical systems. The prebiotic chemistry of formamide affords in a single and simple physical-chemical frame nucleic bases, acyclonucleosides, nucleotides, biogenic carboxylic acids, sugars, amino sugars, amino acids and condensing agents. Thus, we suggest the possibility that formamide could have jointly provided the main components for the onset of both (pre)genetic and (pre)metabolic processes. As a note of caution, we discuss the fact that these observations only indicate possible solutions at the level of organic substrates, not at the systemic chemical level.
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Compared with HCN, formamide yields a wider variety of prebiotic biomolecules because the presence of oxygen allows an interplay of oxygenous and nitrogenous reactive species that is not possible in HCN oligomerization alone.
“In comparison to the chemistry of HCN, the reasons why formamide yields a wider variety of prebiotic biomolecules are diverse.84–89 The presence of oxygen in its structure allows an interplay of oxygenous and nitrogenous reactive species that is not possible in the HCN oligomerization alone.”
From The protometabolic nature of prebiotic chemistry (2023) · cites this paper as [84]
Formamide is the simplest possible hydrolytic product from HCN chemistry and leads to a rich prebiotic chemistry.
“The simplest possible hydrolytic product from the HCN chemistry is formamide, which indeed also leads to a very rich prebiotic chemistry,84 worthy of analysis before inspection of more complex scenarios (see next section).”
From The protometabolic nature of prebiotic chemistry (2023) · cites this paper as [84]
Formamide has specific physical properties and stability features that make it especially suitable as a universal prebiotic starting material.
“Formamide presents, however, specific physical properties and stability features that makes it especially suitable as a universal prebiotic starting material.84,87”
From The protometabolic nature of prebiotic chemistry (2023) · cites this paper as [84]
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References 365 · Cited by 215
- Authors
- Saladino, R., Botta, G., Pino, S., Costanzo, G., & Di Mauro, E.
- Affiliations
- Università degli Studi della Tuscia (IT)
- Sapienza University of Rome (IT)
- Institute of Molecular Biology and Pathology (IT)
- Corresponding author
- Saladino, Raffaele
- Venue
- Chemical Society Reviews
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2012
- Volume
- 41
- Issue
- 16
- Pages
- 5526
- ISSN
- 0306-0012 (ISSN-L)
- 1460-4744
- OpenAlex
- W2060647305
- Cited by
- 215
- References
- 365
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 14 · 2023: 12 · 2022: 11 · 2021: 17 · 2020: 27 · 2019: 21 · 2018: 19 · 2017: 19 · 2016: 14 · 2015: 16 · 2014: 8 · 2013: 17 · 2012: 1
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chemical Society Reviews (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- UnitusOpen (Tuscia University) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- origin of life, formamide, metabolism-first hypothesis, prebiotic chemistry, hypercycles, nucleic acid precursors, RNA precursors, nucleotide synthesis, fatty acid synthesis, amino acids, sugar, amino sugars
- MeSH terms
- Origin of Life, Amino Acids, Carboxylic Acids, Formamides, Hydrogen Cyanide, Minerals, Models, Molecular, Nucleic Acids, Evolution, Chemical, Metabolic Networks and Pathways, Polymerization
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