Flipons and the origin of the genetic code.

Abstract

This paper is focused on the origins of the contemporary genetic code. A novel explanation is proposed for how the mapping of nucleotides in DNA to amino acids in proteins arose that derives from repeat nucleotide sequences able to form alternative nucleic acid structures (ANS), such as the unusual left-handed Z-DNA, triplex, G-quadruplex and I-motif conformations. The scheme identifies sequence-specific contacts that map ANS repeats to dipeptide polymers (DPS). The stereochemistry required naturally evolves into a non-overlapping, triplet code for mapping nucleotides to amino acids. The ANS/DPS complexes form a simple, genetically transmitted, self-templating, autonomously replicating collection of 'tinkers' for Nature to evolve. Tinkers have agency and promote their own synthesis by forming catalytic scaffolds with metals, further enhancing their capabilities. Initial support for the model is provided by computational models built with AlphaFold3. The predictions made are properly falsifiable with the currently available methodology.