In his 2001 article, “Translation: in retrospect and prospect,” the late Carl Woese made a prescient observation that “our current view of translation be reformulated to become an all-embracing perspective about which 21st century Biology can develop” (RNA 7:1055–1067, 2001, https://doi:10.1017/s1355838201010615 ). The quest to decipher the origins of life and the road to the genetic code are both inextricably linked with the history of the ribosome. After over 60 years of research, significant progress in our understanding of how ribosomes work has been made.

The peptidyl transferase center of the modern ribosome has been found to encompass an area of twofold pseudosymmetry (SymR). This observation strongly suggests that the very core of the ribosome arose from a dimerization event between two modest-sized RNAs. It was previously shown that at least four non-standard interactions exist between the two halves of SymR. Herein, we verify that the structure of the SymR is highly conserved with respect to both ribosome transition state and phylogenetic diversity. These comparisons also reveal two additional sites of interaction between the two halves of SymR and refine our understanding of the previously known interactions. In addition, the possible role that magnesium may have in the coordination, stabilization, association, and evolutionary history of the two halves (A-region and P-region) was examined. Together, the results identify a likely site where structural elements and Mg2+ ions may have facilitated the ligation of two aboriginal RNAs into a single unit.

Compared with the large corpus of published work devoted to the study of the origin and early development of anabolism, little attention has been given to the discussion of the early evolution of catabolism in spite of its significance. In the present study, we have used comparative genomics to explore the evolution and phylogenetic distribution of the enzymes that catalyze the extant catabolic pathways of the monosaccharides glucose and ribose, as well as those of the nucleobases adenine, guanine, cytosine, uracil, and thymine. Based on the oxygen dependence of the enzymes, their conservation, and evolution, we speculate on the relative antiquity of the pathways. Our results allow us to suggest which catabolic pathways and enzymes may have already been present in the last common ancestor. We conclude that the enzymatic degradations of ribose, as well as those of purines adenine and guanine, are among the most ancient catabolic pathways which can be traced by protein-based methodologies.

The modern ribosome catalyzes all coded protein synthesis in extant organisms. It is likely that its core structure is a direct descendant from the ribosome present in the last common ancestor (LCA). Hence, its earliest origins likely predate the LCA and therefore date further back in time. Of special interest is the pseudo-symmetrical region (SymR) that lies deep within the large subunit (LSU) where the peptidyl transfer reaction takes place. It was previously proposed that two RNA oligomers, representing the P- and A-regions of extant ribosomes dimerized to create a pore-like structure, which hosted the necessary properties, that facilitate peptide bond formation. However, recent experimental studies show that this may not be the case. Instead, several RNA constructs derived exclusively from the P-region were showed to form a homodimer capable of peptide bond synthesis. This seemingly modest change in our understanding is important because it provides a deeper understanding of ribosome’s history. In practice this will change the focus of future research, which will likely increasingly examine the origins and properties of the P-region. Of special interest will be the origin issues as the homodimer would have allowed a pre-LCA ribosome that was significantly smaller than previously proposed. For the A-region the immediate issue will likely be its origin and whether it enhances ribosome performance. Here, we re-analyze the RNA/RNA interaction regions that most likely lead to SymR formation in the light of these recent findings. Further, it has been suggested that the ability of these RNA constructs to dimerize and enhance peptide bond formation is sequence dependent. We have analyzed the implications of sequence variations as parts of functional and non-functional constructs.

The highly conserved peptidyl transferase center (PTC) of the ribosome contains an RNA pore that serves as the entrance to the exit tunnel. Analysis of available ribosome crystal structures has revealed the presence of multiple additional well-defined pores of comparable size in the ribosomal (rRNA) RNAs. These typically have dimensions of 1-2 nm, with a total area of ∼100 Å 2 or more, and most are associated with one or more ribosomal proteins. The PTC example and the other rRNA pores result from the packing of helices. However, in the non-PTC cases the nitrogenous bases do not protrude into the pore, thereby limiting the potential for hydrogen bonding within the pore. Instead, it is the RNA backbone that largely defines the pore likely resulting in a negatively charged environment. In many but not all cases, ribosomal proteins are associated with the pores to a greater or lesser extent. With the exception of the PTC case, the large subunit pores are not found in what are thought to be the evolutionarily oldest regions of the 23S rRNA. The unusual nature of the PTC pore may reflect a history of being created by hybridization between two or more RNAs early in evolution rather than simple folding of a single RNA. An initial survey of nonribosomal RNA crystal structures revealed additional pores, thereby showing that they are likely a general feature of RNA tertiary structure.