The evolution and functional repertoire of translation proteins following the origin of life

Abstract

Background: The RNA world hypothesis posits that the earliest genetic system consisted of informational RNA molecules that directed the synthesis of modestly functional RNA molecules. Further evidence suggests that it was within this RNA-based genetic system that life developed the ability to synthesize proteins by translating genetic code. Here we investigate the early development of the translation system through an evolutionary survey of protein architectures associated with modern translation.

Results: Our analysis reveals a structural expansion of translation proteins immediately following the RNA world and well before the establishment of the DNA genome. Subsequent functional annotation shows that representatives of the ten most ancestral protein architectures are responsible for all of the core protein functions found in modern translation.

Conclusions: We propose that this early robust translation system evolved by virtue of a positive feedback cycle in which the system was able to create increasingly complex proteins to further enhance its own function.

Figure 1

A popular model for the development of the genetic system. The RNA world hypothesis proposes that the first genetic system involved informational RNA molecules that encoded the synthesis of modestly functional RNA molecules [1]. Protein translation developed during this period leading to the RNA-protein world. Finally, protein enzymes produced deoxyribonucleotides through ribonucleotide reduction. The availability of deoxyribonucleotides led to the establishment of the DNA genome and the modern genetic system [5].

Figure 2

Protein fold expansion plotted as a function of ancestry. Fold expansion is calculated as the cumulative fraction of folds less than or equal to a given ancestry value. Ancestry values for fold architectures were derived from the phylogenetic tree of all folds by Wang et al. [26] and are equal to the number of nodes from a given fold to the root of the phylogenetic tree divided by the number of nodes from the most recent fold to the root of the tree. Fold expansion can be considered a proxy for sophistication while ancestry value can be considered a proxy for evolutionary time. For reference, the same analysis is performed on canonical TCA cycle enzymes, immune system proteins, and the whole proteome (see Results and discussion). The first fold of a ribonucleotide reductase catalytic domain appears at 19% ancestry, while the first fold found in only one taxonomic domain of life appears at 40% ancestry. We use these values to approximate ranges in ancestry value that correspond to the RNA-protein world, the era of the Last Universal Common Ancestor (LUCA), and the era of modern biology. These results reveal a rapid expansion of translation protein architectures before the divergence of LUCA and even before the establishment of the DNA genome. Quantitative features of these results are presented in Table 1.

Figure 3

A summary of functional annotation of the most ancestral translation protein folds. Nine of the ten most ancestral folds identified by Wang et al. [26] are present in translation proteins. The specific functional roles of these folds converge on four general categories: high energy phosphoryl transfer, RNA modification, RNA binding, and protein binding. Exceptions are aminoacylation by tRNA synthetase and tRNA splicing by ribosomal protein S28e. Taken together, the functions imparted by these nine most ancestral folds represent all of the central protein functions in the modern translation system (Figure 4). A summary of the genes in which these folds are found is available as Additional file 2. A detailed annotation of functions imparted by these folds is available as Additional file 3.

Figure 4

A model of protein enhancement in the primitive translation system. The protein functions illustrated here are imparted by the earliest translation protein fold architectures and are summarized in Figure 3. A) The ancestor of the class I aminoacyl tRNA synthetase (ARS) catalytic domain charges tRNAs with amino acids (lowest ancestry value = 5.7%). B) An ancestor of a noncatalytic ARS domain binds tRNA anticodon and interacts with protein "A" during aminoacylation of the tRNA (lowest ancestry value = 1.3%). C) Ancestors of RNA modification enzymes add small organic molecules to tRNA and rRNA to adjust mutual binding affinity (lowest ancestry value = 1.9%). D) Ancestors of regulatory factor domains bind mRNA and tRNA to stabilize their interaction during peptide chain initiation and elongation (lowest ancestry value = 1.3%). E) Ancestors of the regulatory factor GTPases drive peptide elongation forward and sensitize the ribosome to codon-anticodon mismatches (lowest ancestry value = 0.0%). F) Ancestors of ribosomal proteins are able to bind rRNA and one another to stabilize the primitive ribosome complex (lowest ancestry value = 0.6%). These functions were all present before 6% ancestry, indicating that a robust translation system existed early on in the RNA-protein world.

Figure 5

A positive feedback loop mechanism for the early development of the translation system. At each evolutionary stage, the stability and fidelity of the translation system is enhanced by the peptides it produces. This new superior translation system is able to synthesize proteins of even greater functional capability that can, in turn, act on the translation system to further enhance its own functional capability. This mechanism may have been a central driving force in the transition from the RNA world to modern cellular life.