Where does life come from and how can we simulate conditions leading to simple organic molecules?

In 1952, Miller and Urey showed with their famous experiment on chemical evolution that amino acids can be formed in a simulated early earth atmosphere from water, ammonia, methane, and hydrogen in a closed apparatus under a continuous process of evaporation, electric discharges, and condensation. However, no nucleic acids were observed.

Almost ten years later, in 1961, Oro and Kimball demonstrated the formation of adenine and precursors of the purine bases from hydrogen cyanide, ammonia, and water under putative conditions of the primeval earth.

However, the formation of key building blocks required for chemical and biological evolution under early earth conditions remained unclear.

Proposed abiotic formation of furanoside-nucleosides from simple molecules containing hydrogen, carbon, nitrogen, and oxygen. R¹, R² = -NH₂, -OH, -H.

The widely accepted RNA world hypothesis suggests that life first emerged from RNA which was able to (self-)replicate and evolve. Replication of RNA requires the formation of the complementary pyrimidine-purine Watson-Crick base pairs A:U and G:C, which are a prerequisite for the accurate transfer of genetic information. Although prebiotic pathways to RNA building blocks have been reported, no pathway so far was able to generate all four constituents of RNA simultaneously.

This is where the work of Thomas Carell and his co-workers comes into play: They recently reported a new pathway which allows the formation of purine and pyrimidine nucleosides under conditions which match the ones of the prebiotic earth. Their chemistry is driven exclusively by fluctuations of physicochemical parameters such as pH, temperature and concentration, realized by repetitive cycles of evaporation and dissolution in a closed apparatus. In addition, these conditions lead to the parallel formation of a variety of non-canonical purine nucleosides which might represent molecular fossils of an early abiotic world. It is estimated that many of these non-canonical RNA building blocks have been part of the genetic system of the last universal common ancestor.

Next to the formation of nucleosides, the emergence of life as we know it today also required amino acids and the process of translation, in which RNA information encodes the formation of proteins.

In our online workshop entitled “The chemistry behind how life started on Earth” we shed light on the evolution of nucleosides and amino acids, so RNA and peptides.

→ Please register here!

References:

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Prebiotic stereoselective synthesis of purine and noncanonical pyrimidine nucleotide from nucleobases and phosphorylated carbohydrates; H. J. Kim, S. Benner; Proc. Natl. Acad. Sci. 2017; 114(43): 11315-11320. https://doi.org/10.1073/pnas.1710778114

A high-yielding, strictly regioselective prebiotic purine nucleoside formation pathway; S. Becker, I. Thoma, A. Deutsch, T. Gehrke, P. Mayer, H. Zipse, T. Carell; Science 2016; 352(6287): 833-836. https://doi.org/10.1126/science.aad2808

Wet-dry cycles enable the parallel origin of canonical and non-canonical nucleosides by continuous synthesis; S. Becker, C. Schneider, H. Okamura, A. Crisp, T. Amatov, M. Dejmek, T. Carell; Nat. Commun. 2018; 9: 163-171. https://doi.org/10.1038%2Fs41467-017-02639-1

Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides; S. Becker, J. Feldmann, S. Wiedemann, H. Okamura, C. Schneider, K. Iwan, A. Crisp, M. Rossa, T. Amytov, T. Carell; Science 2019; 366(6461): 86-78. https://doi.org/10.1126/science.aax2747

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A prebiotically plausible scenario of an RNA-peptide world; F. Müller, L. Escobar, F. Wu, E. Wegrzyn, M. Nainyte, T. Amatov, C.-Y. Chan, A. Pichler, T. Carell; Nature 2022; 605: 279-284. https://doi.org/10.1038/s41586-022-04676-3

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RNA-Templated Peptide Bond Formation Promotes L-Homochirality; E. Węgrzyn, I. Mejdrová, F. M. Müller, M. Nainytė, L. Escobar, T. Carell; Angew. Chem. Int. Ed. 2024; 63(19): e202319235. https://doi.org/10.1002/anie.202319235