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A New Perspective on the Maillard Reaction and the Origin of Life

Abstract

The Maillard reaction, a spontaneous 'one pot' reaction between amino acids and reducing sugars that occurs at low reactant concentrations and low temperatures, is a good candidate for having played a role in the origin of life on the Earth. In view of the probability that RNA and DNA were preceded by an evolutionary forerunner with a more straightforward prebiotic synthesis, it is a testament to the prescience of Oró and colleagues that, in 1975, they drew attention to the Maillard reaction, in particular evidence that melanoidin polymers (the end-product of the reaction) contain ‘…heterocyclic nitrogen compounds similar to the nitrogenous bases’ (Nissenbaum in J Mol Evol 6:253–270, 1975). Indeed, reports of the Maillard reaction product, 2-Acetyl-6-(Hydroxymethyl)-5,6-Dihydro-4H-Pyridinone (AHDP), with a structure reminiscent of the pyrimidine nucleobase uracil, suggest the Maillard reaction might have played a key role in the synthesis of components of a proto-RNA polymer, with AHDP and two structurally related products predicted to be similar to uracil in the latter's ability to form non-standard base pair interactions. It is possible that the primary function of these interactions was to allow molecules such as AHDP to separate out of the prebiotic chemical clutter. If this were the case, catalysis, and coding—made possible by the polymerization of proto-nucleoside monomers into linear sequence strings—would have been evolving properties.

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Acknowledgements

Thanks to Małgorzata Cabaj for providing the image of the crystal structure of 2',3'-didehydro-2',3'-dideoxyuridine used in Fig. 1C, and to Małgorzata Cabaj and Paulina Dominiak, Ram Krishnamurthy, Jim Cleaves and Bill Hawkins for helpful discussions. Thank you to the reviewers for their constructive criticisms that have improved this manuscript.

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Correspondence to Harold S. Bernhardt.

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The authors dedicate this paper to the late Emeritus Professor George Petersen, the father of DNA in New Zealand, who not only inspired their careers, but influenced many other biochemistry and molecular biology students.

Handling editor: Yitzhak Tor.

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Bernhardt, H.S., Tate, W.P. A New Perspective on the Maillard Reaction and the Origin of Life. J Mol Evol 89, 594–597 (2021). https://doi.org/10.1007/s00239-021-10030-4

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Keywords

  • Origin of life
  • Maillard reaction
  • Pyridinone
  • Pyridone
  • Uracil
  • Uridine
  • RNA