Information is one of the first words that comes up whenever people try to define life. Any living system must be able to store information and pass them on to the next generation. The stored information are instructions used to build the structures and functions necessary for cellular life to operate such as metabolism, membranes, and replication. Modern cellular life relies on protein translation to bridge the gap between information stored in the genome and the structural/functional proteins. In other words, translation reads the genome and turns it into proteins—the structural parts and molecular machines that do most of the work in the cell. Interestingly, translation is a highly complex process that depends on hundreds of proteins and is found in every cellular life form on Earth with virtually no exception. This creates a classic evolutionary puzzle. If translation itself relies on hundreds of proteins, how could it have evolved gradually? How can something so complex evolve step by step? One plausible answer is that translation did not begin as “protein synthesis” in the modern sense. In such scenario, each step can be useful immediately for other purposes, not just in the future protein synthesis machinery.
Translation: a coordinated system
Protein translation is complex process. As mentioned above, translation is the process that converts information stored in nucleic acids to polypeptide sequences (amino acids). The core physical platform where this process takes place is the ribosome, which is an rRNA-protein ribozyme (made of 80+ proteins and rRNAs) that decodes codons and catalyzes peptide-bond formation. The transfer RNAs, charged with an amino acid by a specialized aminoacyl-tRNA synthetase (aaRS) protein, act as adaptors between the code and the functional entity, the protein. Additional factors participate in the process of translation such as initiation, elongation, termination, and recycling factors.
Translation is a coupled network, ribosome structure, tRNA identity, aaRS specificity, and factor-driven kinetics must be mutually compatible for the entire system to work. The target of such enormous machinery is achieving speed, fidelity, and robustness, often via kinetic checkpoints. It is a process made of multiple independent components, and saying “it appeared at once” dodges the key question: how partial intermediates could be favorably selected for at each step?
RNA at the center of the ancient world
The RNA world, a term coined by Walter Gilbert in 1986, refers to a stage in the evolutionary history of life on Earth where RNA molecules thriven and self-replicated before the evolution of DNA and proteins. RNA possesses characteristics that makes it a great candidate for the job of initiating life on Earth. Information can be stored in RNA molecules in order to be later inherited. In addition, RNA molecules can fold into 3D shapes that speed up reactions, called ribozymes. The two vital functions offer a way to imagine biology before DNA and proteins.
If RNA performs both information storage and catalysis, then early translation-like chemistry could have started as RNA-driven reactions later refines by proteins. Thus, what minimal RNA-based molecules could plausibly precede modern translation without requiring a full coordinated system at once? Evolution needs a continuous path. In this sense, every intermediate stage must be selected for and no useless intermediates are permitted. Thus, each step during the evolution of translation from early RNA self-replicators had certain selective advantage, not necessarily directly toward the formation of the entire machinery above.
A step-by-step scenario for early translation
It is important to emphasize that selection, and more generally the chemical evolution, that is discussed in this evolutionary scenario differ from that of Darwinian evolution as there was not yet: discrete individuals, high-fidelity heredity, and long-lived vertical descent. In this pre-Darwinian world, molecules that replicate faster, resist degradation, or catalyze their own production become more abundant, while others stay but with less to none chance to evolve and become more complex. Another important aspect of this proto-life environment are compartmentalized protocells/vesicles where sets of RNAs cooperated, but this is not our focus in this article.
The scenario of translation evolution thus relies on selfish RNA cooperators within a compartment. These RNA cooperators can perform catalytic reactions, for example X->Y. The efficiency of performing such reactions is the trait that affects the fitness of the ribozyme and sets the ground for evolvability.
Step 1: amino acids as helpers
Amino acids bind to some ribozymes on a naturally existing binding site. The binding increases the potency of the ribozyme to catalyze its reaction. The strong stimulation of ribozyme by peptides was demonstrated using in vitro selection (Robertson et al, RNA 2004). The RNA molecule capable of binding an amino acid will eventually be selected for as it outcompetes its peers and a gradual perfection of the amino acid binding sequence and structure takes place.
Step 2: short peptides start to appear
Our little friend, the ribozyme, evolves a peptide ligase activity. The multiple amino acids bound to the ribozyme are linked by the peptide bond to form short oligopeptides. Low specificity, but highly active ribozymes with peptide ligase activity were obtained by in vitro selection. These oligopeptides can be actively selected for as they increase the reactivity of the ribozyme.
Step 3: division of labor
The short peptide, made in step 2, can dissociate from the ribozyme and bind to another ribozyme enhancing its catalytic activity. The interactions drive the evolvability of the system and gives the compartment a selective advantage over other protocells. The various ribozyme start to specialize into specific functions: one focuses on core catalysis/replication-related chemistry while the other becomes better in peptide-making.
Step 4: proto-tRNAs as amino acid carriers
In the busy factory of ribozymes and RNA molecules, small RNAs evolve to help capture amino acids. The accumulation of amino acids in the compartment is a selective advantage as more amino acids means better catalytic activity. The autocatalytic aminoacylation, which evolves within these proto-tRNAs increase the affinity and specificity of the molecule to amino acids. Later, every tRNA molecule will be able to bind to one, and only one amino acid.
Step 5: transpeptidation as the last stitch
Another ribozyme evolves that capacity to bind aminoacylated tRNAs instead of individual amino acids. This will increase spatial precision of binding. The biochemical activity of this ribozyme would be transpeptidation rather than amino acid ligation. This ribozyme represents the progenitor of the large ribosomal subunit.
Conclusion
The evolutionary path depicted here represents a “story of takeover” of the ribozyme functions by evolving proteins. From ribozymes that bind amino acids to ribozymes that aminoacylate RNAs and later other ribozymes that catalyze peptide bonds, protein translation could have started as a side-benefit, not for proteins, but eventually emerged as a highly robust, accurate, and controlled machinery that acts as a factory of proteins.
Reference:
Wolf YI, Koonin EV. On the origin of the translation system and the genetic code in the RNA world by means of natural selection, exaptation, and subfunctionalization. Biol Direct 2, 14 (2007).
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