Interdependence, Reflexivity, Fidelity, Impedance Matching, and the Evolution of Genetic Coding

Abstract

Genetic coding is generally thought to have required ribozymes whose functions were taken over by polypeptide aminoacyl-tRNA synthetases (aaRS). Two discoveries about aaRS and their interactions with tRNA substrates now furnish a unifying rationale for the opposite conclusion: that the key processes of the Central Dogma of molecular biology emerged simultaneously and naturally from simple origins in a peptide•RNA partnership, eliminating the epistemological utility of a prior RNA world. First, the two aaRS classes likely arose from opposite strands of the same ancestral gene, implying a simple genetic alphabet. The resulting inversion symmetries in aaRS structural biology would have stabilized the initial and subsequent differentiation of coding specificities, rapidly promoting diversity in the proteome. Second, amino acid physical chemistry maps onto tRNA identity elements, establishing reflexive, nanoenvironmental sensing in protein aaRS. Bootstrapping of increasingly detailed coding is thus intrinsic to polypeptide aaRS, but impossible in an RNA world. These notions underline the following concepts that contradict gradual replacement of ribozymal aaRS by polypeptide aaRS: 1) aaRS enzymes must be interdependent; 2) reflexivity intrinsic to polypeptide aaRS production dynamics promotes bootstrapping; 3) takeover of RNA-catalyzed aminoacylation by enzymes will necessarily degrade specificity; and 4) the Central Dogma’s emergence is most probable when replication and translation error rates remain comparable. These characteristics are necessary and sufficient for the essentially de novo emergence of a coupled gene–replicase–translatase system of genetic coding that would have continuously preserved the functional meaning of genetically encoded protein genes whose phylogenetic relationships match those observed today.

Class I and II aminoacyl‐tRNA synthetase tRNA groove discrimination created the first synthetase–tRNA cognate pairs and was therefore essential to the origin of genetic coding

“…There is an appealing continuity in this model for codon development, arising initially from aaRS groove discrimination in the acceptor stem. Characteristics of the operational code are consistent with recent suggestions that protein structures evolved coordinately with the alphabet size and that the evolution of the genetic code also traces the discovery of protein folding rules (5). Correlations between secondary and tertiary structures of ribosomal proteins and the estimated order of rRNA additions provoked a similar hypothesis from an entirely different direction (29).…”

“…Embedding that information into tRNA required quasi-specific recognition of opposite grooves of ancestral tRNA minihelices by ancestral Class I and II aminoacyl-tRNA synthetases (aaRS). In another recent publication (5), we noted that prior to the development of genetic coding coded sequence space was necessarily formless and void, until a bidirectional tRNA synthetase protozyme gene (34) simultaneously colonized two disjoint regions, coding for two distinct peptides with amino acid activating activity that each could use to select amino acids from its own class, thereby implementing the reflexive feedback necessary to evolve and refine coding precision.…”

Class I and II aminoacyl-tRNA synthetase tRNA groove discrimination created the first synthetase•tRNA cognate pairs and was therefore essential to the origin of genetic coding

“…There is an appealing continuity in this model for codon development, arising initially from aaRS groove discrimination in the acceptor stem. Characteristics of the operational code are consistent with recent suggestions that protein structures evolved coordinately with the alphabet size and that the evolution of the genetic code also traces the discovery of protein folding rules (4). Correlations between secondary and tertiary structures of ribosomal proteins and the estimated order of rRNA additions provoked a similar hypothesis from an entirely different direction (28).…”

“…Embedding that information into tRNA required quasi-specific recognition of opposite grooves of ancestral tRNA minihelices by ancestral Class I and II aminoacyl-tRNA synthetases. In another recent publication (4), we noted that prior to the development of genetic coding coded sequence space was necessarily formless and void, until a bidirectional tRNA synthetase Protozyme gene (33) colonized two disjoint regions, coding for two distinct peptides with amino acid activating activity that each could use to select amino acids from its own Class, thereby implementing the reflexive feedback necessary to evolve and refine coding precision.…”

Aminoacyl-tRNA synthetase evolution and sectoring of the genetic code

“…As described previously, tRNA Pri evolved initially as an improved mechanism to synthesize polyglycine to stabilize protocells (as in bacterial cell walls) before the coevolution of tRNAomes, aaRS enzymes, ribosomes and the genetic code. Alternate views have been expressed by others [3,4,7,8,44]. …”