Partitioning of aminoacyl-tRNA synthetases in two classes could have been encoded in a strand-symmetric RNA world.

The "chicken-or-egg" dilemma dictates that archaic tRNAs be aminoacylated by ribozymic aminoacyl-tRNA synthetases, rAARSs, with protein synthetases (pAARSs) emerging later and, strikingly in two versions. However, the distribution of these two versions among the codons also suggests their involvement in development of the genetic code. Here we propose a solution to this controversy, which relies on a primordial complementarity hypothesis that in a strand-symmetric RNA world both complementary replicas of many genes could encode the first proteins. Accordingly, if one rearranges the code table in a manner that puts complementary codons directly against each other, an almost perfect mirror symmetry in tRNA aminoacylation by the two groups of synthetases is revealed. Specifically, the pairs of complementary anticodons from the same pAARS class tend to contain RR and YY dinucleotides at first and second versus third and second positions, whereas in pairs of pAARSs from the different classes these positions are occupied by YR and RY, including CG, GC, UA, and AU palindromes. The latter are indistinguishable in complementary anticodons, thus leading to erroneous aminoacylation (note that there is no such problem for RR- and YY-containing complementary anticodons). This can be averted by "spreading out" tRNA recognition by two rAARSs away from the anticodons in the opposite directions, giving two complementary rAARSs. The principle of evolutionary continuity suggests that their protein successors also arose on complementary strands. Our analyses support this hypothesis.