Origin and Evolution of the Ribosome

A major commonality of all cellular life is the coupling between translation and transcription mediated by the genetic code. Comparative genomics has further refined this by revealing the presence of an “RNA metabolism” (Anantharaman et al. 2002) or “Persistent proteome” (Danchin et al. 2007) that is basically a compendium of essentially universal genes involved in translation, transcription, RNA processing and degradation, intermediary and RNA metabolism, and compartmentalization. DNA replication likely arose later because the core enzymes involved in the process are not related (Bailey et al. 2006 and others). Together these universal genes comprise what is frequently referred to as LUCA, the last universal common ancestor (Benner et al. 1993; Lazcano 1994; Mushegian and Koonin 1996; Kyrpides et al. 1999). It is noteworthy that no matter how they are defined, by far the largest numbers of genes in LUCA are associated with translation. Indeed, the translation machinery as represented in LUCA is essentially complete indicating that major events in its origins occurred before LUCA. Thus, it might appear that the origins of the translation machinery would be hopelessly obscured by time. Nevertheless, as will be discussed herein, substantial although necessarily incomplete, evidence relating to the origins and early development of the translation machinery and its relation to other core cellular processes continues to exist in the primary sequences, three-dimensional folding, and functional interactions of the various macromolecules involved in the modern versions of the translation machinery. The modern ribosome consists of small and large subunits (30S and 50S in Bacteria and Archaea) that come together during the initiation of protein synthesis remain together as individual amino acids are added to a growing peptide according to information encoded on the mRNA, and finally separate again in conjunction with the release of the finished protein. Each subunit is an RNA/protein complex. In Bacteria and Archaea, the 50S subunit typically contains a 23S rRNA and a 5S rRNA whereas the 30S subunit contains the 16S rRNA. Peptide bond synthesis occurs in the 50S subunit at the peptidyl transferase center, (PTC), and codon recognition occurs at the decoding site, which is in the small subunit. Transfer RNAs, (tRNA), bridge the two subunits occupying, at various times in the synthesis cycle, the A, P, or E (exit) sites of the 50S subunit and the decoding site in the 30S subunit. A universal CCA sequence at the 3′ end of the tRNA is the point of attachment of the amino acid and later the growing peptide chain to the tRNA. The A, P, and E sites are partly in the small subunit and partly in the large subunit such that a tRNA can be in a hybrid site (e.g., the A site in the 30S and P site in the 50S. The mRNA is exclusively found in the small subunit where it interacts with the anticodon loops of the tRNAs. As the nascent protein is synthesized it passes through an exit tunnel that begins at the PTC center and ultimately exits from the back of the 50S subunit. Synthesis is a dynamic cyclic process in which tRNAs enter the ribosome bringing amino acids as specified by the mRNA and move through the machinery, which undergoes a series of coordinated motions that drive the process (Steitz 2008). These include the movements of the tRNAs between sites, opening and closing of the L1 stalk on the 50S subunit and the ratcheting of the small subunit relative to the large subunit (Frank and Agrawal, 2000), which has recently been elucidated in structural detail (Zhang et al. 2009). Diverse species (Escherichia coli, Haloarcula marismortui, Thermus thermophiles, and Deinococcus radiodurans) are represented among the various atomic resolution ribosome structures now available (Ban et al. 2000; Yusupov et al. 2000; Wimberly et al. 2000; Schuwirth et al. 2005; Selmer et al. 2006; and others). These structures encompass 30S and 50S subunits as well as the whole 70S ribosome. In addition, cryoelectron microscopy studies have revealed dynamic motions associated with the ribosome (Frank and Agrawal 2000; Connell et al. 2007; and others). These ongoing high resolution structural studies provide the opportunity to examine the relative age of features within the ribosome such as the A, P, and E sites, the exit tunnel, the L7/L12 region, and the L1 region that facilitate the entry and exit of tRNAs.