What RNA World? Why a Peptide/RNA Partnership Merits Renewed Experimental Attention

Charles Carter
<span title="2015-01-23">2015</span> <i title="MDPI AG"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/gbzbhas4rfd5pkn6xglvth3dre" style="color: black;">Life</a> </i> &nbsp;
We review arguments that biology emerged from a reciprocal partnership in which small ancestral oligopeptides and oligonucleotides initially both contributed rudimentary information coding and catalytic rate accelerations, and that the superior information-bearing qualities of RNA and the superior catalytic potential of proteins emerged from such complexes only with the gradual invention of the genetic code. A coherent structural basis for that scenario was articulated nearly a decade before
more &raquo; ... demonstration of catalytic RNA. Parallel hierarchical catalytic repertoires for increasingly highly conserved sequences from the two synthetase classes now increase the likelihood that they arose as translation products from opposite strands of a single gene. Sense/antisense coding affords a new bioinformatic metric for phylogenetic relationships much more distant than can be reconstructed from multiple sequence alignments of a single superfamily. Evidence for distinct coding properties in tRNA acceptor stems and anticodons, and experimental demonstration that the two synthetase family ATP binding sites can indeed be coded by opposite strands of the same gene supplement these biochemical and bioinformatic data, establishing a solid basis for key intermediates on a path from simple, stereochemically coded, reciprocally catalytic peptide/RNA complexes through the earliest peptide catalysts to contemporary aminoacyl-tRNA synthetases. That scenario documents a path to increasing complexity that obviates the need for a single polymer to act both catalytically and as an informational molecule. Life 2015, 5 Life 2015, 5 297 absence of transitional links between earlier intermolecular interactions and the triplet code is a fundamental stumbling block that has continued to justify the questionable conclusion that a biologically sufficient set of functional RNA molecules arose by themselves, providing all informational continuity and catalysis [6] necessary to produce the code, without then leaving a trace behind in the phylogenetic record. Reciprocal templating based on the structural complementarity of peptides and RNA proposed by Carter and Kraut affords rudimentary implementation of all necessary functionalities-coding, catalysis, and replication-by far simpler, stepwise processes. The important distinction between this scenario and the RNA World hypothesis is that the requisite specificity is low in the initial stages of the former, but unacceptably high in the latter [7] . Low specificity processes occur with greater frequency and hence are more likely to have occurred first. As the fundamental gap in understanding the origin of life is the emergence of the genetic code, it makes sense to study how the molecular machinery developed that translates that code today: the ribonucleoprotein complexes of aminoacyl-tRNA synthetaseses with their cognate transfer RNAs. A significant unification underlying the origins of translation was the recognition that the two distinct aminoacyl-tRNA synthetase superfamilies are, very probably, fundamentally related to one another, by sense/antisense ancestry. This duality was originally proposed by Rodin and Ohno [8] in response to the recognition that the 20 amino acids were activated and transferred to cognate tRNAs by two entirely distinct superfamilies of aminoacyl-tRNA synthetases [9] [10] [11] . Much of our recent research has tested biochemical [12-16] and bioinformatics [17] predictions of that model, and examined a designed sense/antisense gene with two functional products [18] [19] [20] . "Urzymes" are quite small, highly conserved fragments of the two aminoacyl-tRNA synthetase superfamilies (Figure 3 ). Our biochemical studies have shown that Urzymes from both classes retain ~60% of the Gibbs energies of catalytic proficiency of fully evolved synthetases [13, 14, 21] and ~20% of their specificities for amino acid activation [12, 20] . The catalytic power of peptides related by phylogeny to contemporary enzymes is thus far greater than was anticipated from comparison with the uncatalyzed rate of peptide bond formation, which is ~10 6 -fold slower [22, 23] . This million-fold excess catalytic proficiency argues (i) that such constructs closely resemble true ancestral forms; (ii) that they are themselves highly evolved; and (iii) hence had simpler functional ancestors that might now themselves be experimentally accessible. Second, and less obvious, we showed that synthetase Urzyme coding sequences have a property-high middle-codon base-pairing-expected if these two distinct enzyme families were once encoded on opposite strands of the same ancestral gene [17] , as proposed by Rodin and Ohno [8, 24] . This new metric can therefore also be used to pursue the histories of ancient genes further back into the depths of time than ever before.
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