Ancestral RNA incorporated an expanded set of nucleobases

Many types of nucleobases and modifications are hypothesized to have been present in early RNA.

RNA was always composed of just four canonical bases

Adenine( A) , uracil (U), guanine(G), and cytosine(C) are the dominant bases found in extant RNA and are the only base inheritance from early RNA.
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Rebecca Guth-Metzler   Subscribe ...


Prebiotic base and nucleoside availability


Alternative bases or nucleosides with alternative bases were prebiotically available for incorporation into life.

eNon-canonical bases were delivered to Earth by meteorites and formed in prebiotically plausible reactions.

eThe non-canonical base 6-aminouracil is reactive to form the necessary glycosidic bond while uracil is not.

eThe non-canonical base urazole is reactive to form the glycosidic bond and preserves the same base pairing face as uracil.


Canonical bases may have been higher in abundance relative to non-canonical bases.

eIn a unifying prebiotic chemical synthesis of both purine and pyrimidine nucleosides, only the canonical nucleosides accumulate as products.


Non-canonical bases structurally mimic RNA properties with canonical bases.

eNon-canonical bases self-assemble by base pairing into polymerization-ready stacks.


Non-canonical bases warp RNA structure and interrupt central RNA interactions.

eNon-canonical bases synthetically added to nucleic acids cause structural, functional, or polymerization problems.


Non-canonical bases are part of the modern RNA repertoire.

eNon-canonical bases are ubiquitous and functional in modern RNA.


Genetic makeup from the time before the first cellular life to now only shows compatibility with the canonical bases.

eThe genetic code, necessary for all biological protein translation, only contains canonical bases.

eModern RNAs largely do not contain records inherited from the first RNAs, so arguments for other bases are only speculative.

eNon-canonical bases mutate to canonical bases after multiple rounds of replication.