Piecemeal Buildup of the Genetic Code, Ribosomes, and Genomes from Primordial tRNA Building Blocks

Abstract

Abstract:The origin of biomolecular machinery likely centered around an ancient and central molecule capable of interacting with emergent macromolecular complexity. tRNA is the oldest and most central nucleic acid molecule of the cell. Its co-evolutionary interactions with aminoacyl-tRNA synthetase protein enzymes define the specificities of the genetic code and those with the ribosome their accurate biosynthetic interpretation. Phylogenetic approaches that focus on molecular structure allow reconstruction of evolutionary timelines that describe the history of RNA and protein structural domains. Here we review phylogenomic analyses that reconstruct the early history of the synthetase enzymes and the ribosome, their interactions with RNA, and the inception of amino acid charging and codon specificities in tRNA that are responsible for the genetic code. We also trace the age of domains and tRNA onto ancient tRNA homologies that were recently identified in rRNA. Our findings reveal a timeline of recruitment of tRNA building blocks for the formation of a functional ribosome, which holds both the biocatalytic functions of protein biosynthesis and the ability to store genetic memory in primordial RNA genomic templates.

Coding of Class I and II Aminoacyl-tRNA Synthetases

“…In particular, Caetano-Anolles [174] now recognizes that the P-loop hydrolase domain genes are among the more ancient genes, without acknowledging that the Class I protozyme appears to be a reasonable ancestral form, not only of the Class I synthetases, but also of the P-loop hydrolases themselves.…”

“…Thus, whereas it is possible in principle, even in the face of horizontal gene transfer [178], to attempt to establish a tree along which the aaRS genes radiated to enlarge the amino acid alphabet, no such exercise appears possible yet for their cognate tRNAs. It is possible that the approaches used by Caetano-Anollès [174] are capable of identifying appropriate patterns in the tRNA multiple sequence alignments, but thus far, that does not appear to have been a goal. Thus, a full understanding of the “tree” of amino acid acylation to tRNA in the emergence of translation, even in principle, appears still to lie ahead.…”

Self-Referential Encoding on Modules of Anticodon Pairs—Roots of the Biological Flow System

“…Ribosomal proteins belong to the category of Intrinsically Disordered [35], which is a character of the early encodings in the SRM. Recent studies have even detected the possibility of ribosomal proteins being coded for by ribosomal RNA [87], extending and updating our older propositions [84,85] on tRNA-rRNA homologies that are consistent also with [95].…”

“…Other instances of proteins active in NRPS show homologies to synthetases class I, closer to the Tyr-and TrpRS, and do not activate amino acids but utilize a couple of aminoacyl-tRNAs to promote sequential reactions for peptide synthesis and cyclo-dehydration. These proteins are dated earlier than the translation machinery [95,100]. The diversity in NRPS is large but the two examples collected here suggest an intriguing analogy with the bipartite structure of tRNAs -one segment for the aminoacylation activity, the other for the anticodon.…”

Homocysteine Editing, Thioester Chemistry, Coenzyme A, and the Origin of Coded Peptide Synthesis †

“…Other misactivated amino acids are edited at the catalytic domain, a dedicated editing domain, or both [11,31]. Phylogenetic analyses of structural domains present in proteomes [34] suggest that catalytic domains of AARSs belong to the oldest fold families and may have appeared about 3.7 billion years ago, while separate domains that edit misacylated tRNA appeared later, about 3.2 billion years ago [35] (these timelines are based on counting relative node, i.e., branch point, distance in the rooted trees and using a molecular clock of protein folds to convert relative age into geological time [36]).…”