On the origin of the translation system and the genetic code in the RNA world by means of natural selection, exaptation, and subfunctionalization

Abstract

Background: The origin of the translation system is, arguably, the central and the hardest problem in the study of the origin of life, and one of the hardest in all evolutionary biology. The problem has a clear catch-22 aspect: high translation fidelity hardly can be achieved without a complex, highly evolved set of RNAs and proteins but an elaborate protein machinery could not evolve without an accurate translation system. The origin of the genetic code and whether it evolved on the basis of a stereochemical correspondence between amino acids and their cognate codons (or anticodons), through selectional optimization of the code vocabulary, as a "frozen accident" or via a combination of all these routes is another wide open problem despite extensive theoretical and experimental studies. Here we combine the results of comparative genomics of translation system components, data on interaction of amino acids with their cognate codons and anticodons, and data on catalytic activities of ribozymes to develop conceptual models for the origins of the translation system and the genetic code.

Results: Our main guide in constructing the models is the Darwinian Continuity Principle whereby a scenario for the evolution of a complex system must consist of plausible elementary steps, each conferring a distinct advantage on the evolving ensemble of genetic elements. Evolution of the translation system is envisaged to occur in a compartmentalized ensemble of replicating, co-selected RNA segments, i.e., in a RNA World containing ribozymes with versatile activities. Since evolution has no foresight, the translation system could not evolve in the RNA World as the result of selection for protein synthesis and must have been a by-product of evolution drive by selection for another function, i.e., the translation system evolved via the exaptation route. It is proposed that the evolutionary process that eventually led to the emergence of translation started with the selection for ribozymes binding abiogenic amino acids that stimulated ribozyme-catalyzed reactions. The proposed scenario for the evolution of translation consists of the following steps: binding of amino acids to a ribozyme resulting in an enhancement of its catalytic activity; evolution of the amino-acid-stimulated ribozyme into a peptide ligase (predecessor of the large ribosomal subunit) yielding, initially, a unique peptide activating the original ribozyme and, possibly, other ribozymes in the ensemble; evolution of self-charging proto-tRNAs that were selected, initially, for accumulation of amino acids, and subsequently, for delivery of amino acids to the peptide ligase; joining of the peptide ligase with a distinct RNA molecule (predecessor of the small ribosomal subunit) carrying a built-in template for more efficient, complementary binding of charged proto-tRNAs; evolution of the ability of the peptide ligase to assemble peptides using exogenous RNAs as template for complementary binding of charged proteo-tRNAs, yielding peptides with the potential to activate different ribozymes; evolution of the translocation function of the protoribosome leading to the production of increasingly longer peptides (the first proteins), i.e., the origin of translation. The specifics of the recognition of amino acids by proto-tRNAs and the origin of the genetic code depend on whether or not there is a physical affinity between amino acids and their cognate codons or anticodons, a problem that remains unresolved.

Conclusion: We describe a stepwise model for the origin of the translation system in the ancient RNA world such that each step confers a distinct advantage onto an ensemble of co-evolving genetic elements. Under this scenario, the primary cause for the emergence of translation was the ability of amino acids and peptides to stimulate reactions catalyzed by ribozymes. Thus, the translation system might have evolved as the result of selection for ribozymes capable of, initially, efficient amino acid binding, and subsequently, synthesis of increasingly versatile peptides. Several aspects of this scenario are amenable to experimental testing.

Figure 1

The Eigen threshold for replication fidelity. Fitness could potentially increase with the increase of the genome size and replication fidelity. However, exceeding the genome size limit, imposed by the fidelity that is attainable at the given point in evolution, leads to the "Error Catastrophe" [3], illustrated here as the "Eigen Cliff".

Figure 2

The Darwin-Eigen cycle. The Darwin-Eigen cycle, driven, in part, by selection and, in part, by drift, provides the path to the increasing complexity in course of the evolution of biological systems.

Figure 3

A crude stereochemical model of a direct interaction of two amino acid with a hexanucleotide representing their cognate codons.

Figure 4

Origin of the translation system and the genetic code in the RNA World. Step 0 (the pre-requisite): a ribozyme R catalyzes an arbitrary reaction beneficial for an ensemble of selfish cooperators.

Figure 5

Origin of the translation system and the genetic code in the RNA World. Step 1: amino acids stimulate the activity of the ribozyme R.

Figure 6

Origin of the translation system and the genetic code in the RNA World. Step 2: the ribozyme R evolves an additional enzymatic activity, that of a peptide ligase; enhanced stimulation of the original reaction by the synthesized peptide ensues. One of the joined substrates is likely to be an activated amino acid derivative, such as an aminoacyl adenylate (see text).

Figure 7

Origin of the translation system and the genetic code in the RNA World. Step 3: a peptide with generic ribozyme-stimulating properties is released from the ribozyme R and stimulates the activity of a distinct ribozyme E.

Figure 8

Origin of the translation system and the genetic code in the RNA World. Step 4: the original activity of the ribozyme R (X-Y) and the peptide ligase activity are apportioned between two ribozymes as the result of duplication and subfunctionalization; the ancestor of the large ribosomal subunit (R_L) emerges.

Figure 9

Origin of the translation system and the genetic code in the RNA World. Step 5: Small amino-acid-binding RNAs (T RNAs) evolve via selection for accumulation of amino acids. Once species of the T RNAs evolves the capacity of autocatalytic aminoacylation, further enhancing amino acid accumulation, The actual substrate, probably, was an activated amino acid derivative, such as an aminoacyl adenylate.

Figure 10

Origin of the translation system and the genetic code in the RNA World. Step 6: Amino-acid-specific variants of RNA T evolve by duplication and subfunctionalization. The specifics of T RNA-amino acid interaction depend on the mode amino acid recognition, CRM, ARM, or FAM. A. ARM: recognition of the amino acid residue by the anticodon loop and of the amino acid backbone by the stem of the RNA T. B. ARM: formation of dimers facilitates the stereochemically unhindered binding of amino acids. C. CRM: RNA T exists in two alternative folding conformations. In one conformation, the codon is complementary paired with the anticodon; in the other confirmation, the codon binds a cognate amino acid, and the anticodon is exposed. D. FAM: the amino acid is recognized by an "ad hoc" site unrelated to the codon or the anticodon.

Figure 11

Origin of the translation system and the genetic code in the RNA World. Step 7: The proto-large subunit, R_L, evolves the capacity to bind aminoacyl-T RNAs, resulting in more precise amino acid positioning on R_L. The activity of R_L switches from amino acid ligation to transpeptidation, resulting in an increased peptide yield.

Figure 12

Origin of the translation system and the genetic code in the RNA World. Step 8: An accessory RNA subunit, R_S (progenitor of the small ribosomal subunit), capable of binding aminoacyl-T RNAs through interaction between complementary base triplets.

Figure 13

Origin of the translation system and the genetic code in the RNA World. Step 9: Amino-acid-specific variants of R_S evolve by duplication and subfunctionalization.

Figure 14

Origin of the translation system and the genetic code in the RNA World. Step 10: The proto-small subunit, R_S, evolves the capacity to accommodate external RNA molecules as templates for aminoacyl-T RNA binding.

Figure 15

Origin of the translation system and the genetic code in the RNA World. Step 11: The R_LR_S complex (the protoribosome) evolves the mRNA translocation mechanism. A primitive version of translation evolves.