Peptide bond formation catalyzed on the ribosome is a crucial event in the life on earth. The ribosome is a supercomplex of ribonucleoprotein particles containing both RNAs and proteins, and the peptide bond is produced on the peptidyl transferase center (PTC) of the large subunit of the ribosome. The high-resolution structures of the ribosome showed that the PTC is composed of only RNA. Although the ribosome seems to be a ribozyme, the foundation of the PTC and the evolutionary route of the ribosome are not clear. In this study, a possible evolutionary pathway for ribosome formation has been presented by combining a model experiment and the structural analysis of the ribosome. The current ribosome-catalyzed reaction could have evolved from a primitive system in the RNA world comprising proto-tRNA molecules like the minihelix. The missing link in the evolutionary route of the modern ribosome can be solved by considering tRNAs as primordial molecules comprising proto-ribosomes and proto-tRNAs, which form a symmetrical RNA dimer to constitute the PTC.

  Chiral-selective aminoacylation of an RNA minihelix (progenitor of the modern tRNA) could provide a crucial clue to solve the origin of homochirality in a biological system. In this reaction, an amino acid donor (aminoacyl phosphate oligonucleotide) is placed in close proximity to minihelix with the help of a bridging oligonucleotide, which possesses sequences complementary to both donor nucleotide and single-stranded NCCA of minihelix, to accomplish the chiral (L-amino acid)-selective aminoacylation of the minihelix. Here, we propose a molecular mechanism of chiral selectivity based on the mutational analysis of the donor and bridging nucleotides. The selectivity for L-amino acids is dependent on the stereochemistry of RNA. Due to cation coordination and sugar pucker, the side chain of D-amino acids is brought much closer to the terminal adenosine of the minihelix, thereby causing steric hindrance of the D-amino acids during amino acid transfer from the donor nucleotide to minihelix. This mechanism completely explains the result of the original chiral-selective aminoacylation experiment without any contradictions. This selective process may have determined the homochirality of L-amino acids in the putative RNA world.

This article is dedicated to the memory of Dr. Kaoru Harada.

Twenty amino acids used for protein synthesis during the translation processes, are often called as Magic 20. When and how members of the magic 20 are selected are fundamental subjects for the studies on origins of life. The magic 20 shares three common chemical features; (1) all are so-to-speak "alpha amino acids", that is, the alpha carbon atom is combined with one each of amino group and carboxyl group, (2) the alpha carbon atom of all members is also combined with a hydrogen atom and this hydrogen atom is seated at the specific site of the alpha carbon given raise to L-amino acids if the last position is occupied with any atoms or groups other than hydrogen, and (3) the last position remained at the alpha carbon is substituted with either hydrogen atom or methyl or substituted methyl groups. At moment, any chemical evolution experiment so far carried out could not explain the origin of these unique features of chemical structure. The selection of side chain structures seems to be fortuitous or fitful since no rational basis can be found. The author encourages artificial life-synthesis studies rather than simulated primitive-earth experiments to understand the origins of the magic 20.

This article is dedicated to the memory of Dr. Kaoru Harada.