Chiral histidine selection by D-ribose RNA

Abstract

The invariant choice of L-amino acids and D-ribose RNA for biological translation requires explanation. Here we study this chiral choice using mixed, equimolar D-ribose RNAs having 15, 18, 21, 27, 35, and 45 contiguous randomized nucleotides. These are used for simultaneous affinity selection of the smallest bound and eluted RNAs using equal amounts of L-and D-His immobilized on an achiral glass support, with racemic histidine elution. The experiment as a whole therefore determines whether RNA containing D-ribose binds L-histidine or D-histidine more easily (that is, by using a site that is more abundant/ requires fewer nucleotides). The most prevalent/smallest RNA sites are reproducibly and repeatedly selected and there is a four-to sixfold greater abundance of L-histidine sites. RNA's chiral D-ribose therefore yields a more frequent fit to L-histidine. Accordingly, a D-ribose RNA site for L-His is smaller by the equivalent of just over one conserved nucleotide. The most prevalent L-His site also performs better than the most frequent D-His site-but rarer D-ribose RNAs can bind D-His with excellent affinity and discrimination. The prevalent L-His site is one we have selected before under very different conditions. Thus, selection is again reproducible, as is the recurrence of cognate coding triplets in these most probable L-His sites. If our selected RNA population were equilibrated with racemic His, we calculate that L-His would participate in seven of eight His:RNA complexes, or more. Thus, if D-ribose RNA were first chosen biologically, translational L-His usage could have followed.

It Takes Two to Evolve Too. The Hypothesis on Three Primary Communication Transitions in Evolution

“…However, attachment of just one L-amino acid (in contrast to PNA, amino acids are always chiral, but most likely were synthesized abiotically as a racemate, hence a choice of L-enantiomer would be a contingency) might have shifted helix handedness and increased activity. It correlates well with the observed preferential stereochemical interaction between L-amino acids and D-ribose RNA [82,83]. And finally, the production of the PNA backbone monomer unit has been discovered in cyanobacteria [84] that can be a vestige of PNA World.…”

Recurrent RNA motifs as scaffolds for genetically encodable small-molecule biosensors

“…This number of sequences is theoretically fully represented in the initial pool of RNA with at least 5-fold redundancy. While this is substantially lower diversity than what is recommended for deep selection 24 , aptamers have been attained from starting pools with an even more limited sampling of sequence space 25 .…”

Thresholds in Origin of Life Scenarios

“…Indeed, a racemic mixture of oligonucleotides (region β in Figure 4 D) could break its symmetry because of a triggered small enantiomeric excess amplified by an autocatalytic reaction leading either to L-ribose RNA only (region γ) or to D-ribose RNA only (region δ) ( Hawbaker and Blackmond, 2019 ). Entrenchment would follow with peptide synthesis: L-ribose RNA systems could imply D-amino acids peptides only (region ϕ), whereas D-ribose RNA systems could imply L-amino acids peptides only (region ε) ( Illangasekare et al., 2010 ).…”