Figure 6. Superposition of Class I and II aminoacyl-tRNA synthetases (aaRS) reveals similar hierarchies. Horizontal color bars indicate successive removal of anticodon-binding domains, insertion domains within the catalytic domain to yield Urzymes,and amino acid binding sites to yield Protozymes. Vertical bars indicate parallel successive loss in free energy for transition-state stabilization, which is quantitatively the same for Class I and II aaRS.
Figure 7. The Rodin-Ohno hypothesis that ancestral Class I and II aaRS were originally coded on opposite strands of the same bidirectional gene makes three hypotheses. We have validated each prediction.
Figure 8. Bidirectional genetic coding is an bizarre and counter-intuitive notion The unique information in any gene is restricted to a single strand, as the complementary strand can always be used as a template to recover the original strand. Yet, the evidence is now quite strong that the first genes actually gave distinct interpretations to the coded products from both strands, as suggested by the image of tigers and trees..
Figure 9. Amino acid side chains have two orthogonal properties–size and polarity–that determine how proteins fold. Experimental metrics of these properties are associated with the bases that determine which tRNA is recognized by an aaRS. Size correlates with acceptor stem bases (green), polarity with the anticodon (red). This suggests that the acceptor stem functioned before the anticodon and that it must have developed coding characteristics consistent with the aaRS duality, consistent with the fact that side chain size is the only quantity that is highly correlated to that duality. Class I amino acids are uniformly larger, Class II amino acids are smaller.
Figure 10. The tRNA acceptor stem bases the critical signals for recognition by Class I and II aaRS, Specific recognition in cognate aaRS/tRNA pairs combines specific bases near the acceptor stem that differentially impact the stability of the continuous extended 3′-terminal helix. An uninterrupted helical extension is recognized by Class II aaRS from the major groove. Class I aaRS favor formation of a hairpin and bind from the minor groove. Acceptor-stem bases also represent a palimpsest of the codon-anticodon pairing formed today between tRNA anticodons and mRNA, suggesting a possible origin of the anticodon stem-loop by gene duplication and recombination..
Figure 11. Boot-block for Nature’s OS. The ancestral bidirectional gene together with the nanosensing enabled by the tRNA acceptor stem bases, compose a necessary and sufficient reflexive feedback loop to initiate the search for optimal genetic codes and coding sequences.