From initial RNA encoding to the Standard Genetic Code

Abstract

AbstractMultiple prior experiments show that RNA binds chemically varied amino acids within specific oligonucleotide sequences. The smallest, simplest, and therefore most likely primitive RNA binding sites frequently contain conserved triplets corresponding to the Standard Genetic Code (SGC). Here, the implications of such cognate coding triplets are calculated, combining them with an optimized kinetic model for SGC evolution. RNA-amino acid interactions at obseved frequencies choose an SGC-like code, and, using the same mechanism, effectively resist alternative triplet assignments. Resistance to other kinds of coding is evident across varied code initiation scenarios. RNA-mediated assignments at experimental frequencies are sufficient to guide the ‘ribonucleopeotide (RNP) transition’ to a modern RNP code. This can account for extreme selection of the SGC among its astronomical code possibilities; very SGC-like codes are ca. 1/50 to 1/5 of codes within such a population. Nevertheless, full accounting depends on RNA affinities yet unmeasured. Such a code begins as mostly stereochemical, excludes mismatched assignments, and critically relies on properties characteristic of fusible microbes. After its RNP transition in a partially assigned code, evolution accelerates definitively. Other assignment methods (adaptation, co-evolution, revised stereochemistry, LGT) likely complete the modern SGC because stable cellular intermediates with > 1 code exist, allowing compartmental code exchanges. Though initiated using chemical affinities, the 83 order-of-magnitude focus required to find a near-complete SGC among all possible codes was made by sequential evolutionary anthologies, in successive biological settings.