The proto-ribosome: (a) The symmetrical region within the 23S rRNA of E. coli ribosome (PDB code 2AW4). The A- and P-subregions, in blue and green, respectively, throughout. Helices H68-H71 were removed to reveal the PTC area. (b) 2D scheme of the symmetrical region (on colored background), drawn in a manner exhibiting the twofold symmetry, with the central loop of domain V (C-loop) at its center. The sequence assigned to the remnant of the DPR (boundary marked) is composed of two L-shaped molecules, the A- and P-DPR monomers. Nucleotides conserved by more than 97% in each of the three life domains, as detected in the CRW site [77], are presented by capital letters and the remaining nucleotides by circles. (c) Overlap of the DPR fold as found in the high-resolution structures of archaea (PDB code 1VQ6), bacteria (PDB code 2WDL), and eukarya (PDB code 3U5D) ribosomes, portraying its extreme tertiary conservation in the three life domains. The pocket is projected approximately along the symmetry axis, with the reactants (PDB code 2WDL) positioned at the bottom of the cavity. (d) Overlap of the A- and P-DPR monomers from E. coli (PDB code 2AW4), obtained by rotating one monomer by 179.6° around the symmetry axis. The projection direction is perpendicular to the one shown in (c). tRNA molecule (PDB code 4TRA, in gray) is overlaid with its anticodon arm overlapping H89 and H93 helices from the P- and A-monomers, respectively. Magnified nucleotides from the superimposed stems of H89 and its symmetry-related H93 depict the conformational match. Nucleotide A2602, which is functionally active, bulges into the PTC and breaks the overall symmetry. (e) Model of a minimal coded proto-ribosome assembled from four L-shaped entities of about 60–70 nucleotides each (derived from PDB code 1VY4), i.e., the A-, P-DPR monomers, the proto-SSU (purple), and the bridging element (dark red), complexed with mRNA (orange) and tRNA (cyan). — LIFE
To track down the possible roots of life, various models for the initial living system composed of different combinations of the three extant biopolymers, RNA, DNA, and proteins, are presented.
The suitability of each molecular set is assessed according to its ability to emerge autonomously, sustain, and evolve continuously towards life as we know it.
The analysis incorporates current biological knowledge gained from high-resolution structural data and large sequence datasets, together with experimental results concerned with RNA replication and with the activity demonstrated by standalone constructs of the ribosomal Peptidyl Transferase Center region. The scrutiny excludes the DNA–protein combination and assigns negligible likelihood to the existence of an RNA–DNA world, as well as to an RNA world that contained a replicase made of RNA.
It points to the precedence of an RNA–protein system, whose model of emergence suggests specific processes whereby a coded proto-ribosome ribozyme, specifically aminoacylated proto-tRNAs and a proto-polymerase enzyme, could have autonomously emerged, cross-catalyzing the formation of each other.
This molecular set constitutes a feasible starting point for a continuous evolutionary path, proceeding via natural processes from the inanimate matter towards life as we know it.
Explorers Club Fellow, ex-NASA Space Station Payload manager/space biologist, Away Teams, Journalist, Lapsed climber, Synaesthete, Na’Vi-Jedi-Freman-Buddhist-mix, ASL, Devon Island and Everest Base Camp veteran, (he/him) 🖖🏻
