It is widely believed that the functional properties (phenotype) of a nucleic acid molecule cannot be recapitulated in a different genetic polymer of the same nucleic acid sequence (genotype), yet exceptions to this rule do exist. These include an RNA dopamine aptamer that continues to bind dopamine when the primary sequence is synthesized as DNA and a DNA G-quartet structure that binds hemin and continues to exhibit peroxidase activity when the sequence is constructed as RNA. We refer to such examples as ‘transliteration’—a term borrowed from linguistics that describes cases in which the phenotype of a nucleic acid molecule is retained when the genotype is written in a different genetic language. In this talk, I will extend the concept of transliteration to include examples of synthetic genetic polymers (XNAs) that were isolated by in vitro selection for their ability to site-specifically cleave an RNA substrate. These examples expand the concept of transliteration from nucleic acid molecules that function primarily as receptors to those that function as enzymes. Although more work is needed to understand the structural similarities and distribution of transliteration events in sequence space, the occurrence of these events in natural and synthetic polymers raises the question of whether transliteration is a structural anomaly or possible evolutionary path between different nucleic acid worlds?

Transliteration of synthetic genetic polymers: Structural anomaly or evolutionary portal for genetic takeover?

ACS Spring Meeting 2021

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