Abstract
BackgroundSynthesis of proteins is based on the genetic code - a nearly universal assignment of codons to amino acids (aas). A major challenge to the understanding of the origins of this assignment is the archetypal "key-lock vs. frozen accident" dilemma. Here we re-examine this dilemma in light of 1) the fundamental veto on "foresight evolution", 2) modular structures of tRNAs and aminoacyl-tRNA synthetases, and 3) the updated library of aa-binding sites in RNA aptamers successfully selected in vitro for eight amino acids.ResultsThe aa-binding sites of arginine, isoleucine and tyrosine contain both their cognate triplets, anticodons and codons. We have noticed that these cases might be associated with palindrome-dinucleotides. For example, one-base shift to the left brings arginine codons CGN, with CG at 1-2 positions, to the respective anticodons NCG, with CG at 2-3 positions. Formally, the concomitant presence of codons and anticodons is also expected in the reverse situation, with codons containing palindrome-dinucleotides at their 2-3 positions, and anticodons exhibiting them at 1-2 positions. A closer analysis reveals that, surprisingly, RNA binding sites for Arg, Ile and Tyr "prefer" (exactly as in the actual genetic code) the anticodon(2-3)/codon(1-2) tetramers to their anticodon(1-2)/codon(2-3) counterparts, despite the seemingly perfect symmetry of the latter. However, since in vitro selection of aa-specific RNA aptamers apparently had nothing to do with translation, this striking preference provides a new strong support to the notion of the genetic code emerging before translation, in response to catalytic (and possibly other) needs of ancient RNA life. Consistently with the pre-translation origin of the code, we propose here a new model of tRNA origin by the gradual, Fibonacci process-like, elongation of a tRNA molecule from a primordial coding triplet and 5'DCCA3' quadruplet (D is a base-determinator) to the eventual 76 base-long cloverleaf-shaped molecule.ConclusionTaken together, our findings necessarily imply that primordial tRNAs, tRNA aminoacylating ribozymes, and (later) the translation machinery in general have been co-evolving to ''fit'' the (likely already defined) genetic code, rather than the opposite way around. Coding triplets in this primal pre-translational code were likely similar to the anticodons, with second and third nucleotides being more important than the less specific first one. Later, when the code was expanding in co-evolution with the translation apparatus, the importance of 2-3 nucleotides of coding triplets "transferred" to the 1-2 nucleotides of their complements, thus distinguishing anticodons from codons. This evolutionary primacy of anticodons in genetic coding makes the hypothesis of primal stereo-chemical affinity between amino acids and cognate triplets, the hypothesis of coding coenzyme handles for amino acids, the hypothesis of tRNA-like genomic 3' tags suggesting that tRNAs originated in replication, and the hypothesis of ancient ribozymes-mediated operational code of tRNA aminoacylation not mutually contradicting but rather co-existing in harmony.ReviewersThis article was reviewed by Eugene V. Koonin, Wentao Ma (nominated by Juergen Brosius) and Anthony Poole.
Highlights
Synthesis of proteins is based on the genetic code - a nearly universal assignment of codons to amino acids
The first ("key-lock”) idea assumes some sort of direct stereochemical affinity between amino acids and oligonucleotides that are similar to, or just contain, anticodons [13,14,15,16]
The logical difficulty with this idea is that it does not really address the issue of the code origin — it “passes the buck” to the aforementioned adaptors. We know that these adaptors are not in the least hypothetical — they do exist, they are transfer RNA (tRNA) (Figure 1C), and it is these molecules in which one usually looks for the clues towards elucidation of the code origin
Summary
Synthesis of proteins is based on the genetic code - a nearly universal assignment of codons to amino acids (aas). Genetic Code refers to a nearly universal assignment of triplets (codons) of nucleotides (nts) to amino acids (aas), linking hereditary entities to the functional blocks of life (Figure 1A). This codon-to-aa assignment is realized through the agencies of 1) the code adaptor molecules of transfer RNAs (tRNAs) with a codon’s complementary replica (anticodon) and the corresponding aa attached to the 3’ end, and 2) aminoacyl tRNA synthetases (aaRSs), the enzymes that recognize and connect proper aa and tRNAs (Figure 1B and 1C). The very existence of the two languages (with the code being a translational intermediary) implies an evolutionary motivation This is a great challenge to evolutionists, even at the most abstract conceptual level of reasoning. Because life never evolves with foresight, we inevitably arrive to the hypothesis that the code emerged before translation - in response to the needs of the RNA world (ibid)
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