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bioRxiv · 10.64898/2026.10.08.757769

Compatible Comma-Free Codes and the Origin of the Genetic Code

Boyle, L.
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Abstract

The genetic code is the rule that (apart from minor modifications) is used by all contemporary life on Earth to translate genes into proteins. It is summarized by a 4x4x4 table which maps the 64 possible triplet RNA codons to the 20 canonical amino acids ("AAs"). Understanding the origin of this code is a fundamental open problem in biology. We review the idea of a comma-free code, and put forward a general reason to suspect the primordial code was comma-free (even though the modern code is not). We explain why this primordial code should then persist as a comma-free subcode within the modern code, and identify the five optimal candidates for such a subcode. We then introduce the idea of "compatible comma-free codes" and explain how they allow multiple codes to evolve in parallel, circumventing a standard argument suggesting that code evolution should effectively freeze when the associated genome becomes sufficiently complex. In particular, we highlight the possibility that the original code was a comma-free doublet code, which was then overtaken by a compatible comma-free triplet code, which finally evolved (after the evolution of the start codon and ribosome) to the modern saturated triplet code. To assess this idea, we classify all inequivalent compatible comma-free doublet-triplet codes and, among these, identify the three most promising predecessors of the modern code. Consistency between these three best codes and the "wobble rules" in gene translation provide non-trivial evidence for this possibility.

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Boyle, L.. 2026-10-10. Compatible Comma-Free Codes and the Origin of the Genetic Code. https://doi.org/10.64898/2026.10.08.757769

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