Evolution of Life on Earth: tRNA, Aminoacyl-tRNA Synthetases and the Genetic Code

Abstract

Life on Earth and the genetic code evolved around tRNA and the tRNA anticodon. We posit that the genetic code initially evolved to synthesize polyglycine as a cross-linking agent to stabilize protocells. We posit that the initial amino acids to enter the code occupied larger sectors of the code that were then invaded by incoming amino acids. Displacements of amino acids follow selection rules. The code sectored from a glycine code to a four amino acid code to an eight amino acid code to an ~16 amino acid code to the standard 20 amino acid code with stops. The proposed patterns of code sectoring are now most apparent from patterns of aminoacyl-tRNA synthetase evolution. The Elongation Factor-Tu GTPase anticodon-codon latch that checks the accuracy of translation appears to have evolved at about the eight amino acid to ~16 amino acid stage. Before evolution of the EF-Tu latch, we posit that both the 1st and 3rd anticodon positions were wobble positions. The genetic code evolved via tRNA charging errors and via enzymatic modifications of amino acids joined to tRNAs, followed by tRNA and aminoacyl-tRNA synthetase differentiation. Fidelity mechanisms froze the code by inhibiting further innovation.

Keywords: Elongation Factor-Tu latch; aminoacyl-tRNA synthetase; evolution; genetic code; last universal common cellular ancestor; origin of life; polyglycine; tRNA.

Figure 1

A model for evolution of life on Earth. Evolution of tRNA and translation systems leads to the first cells. A small number of ribozymes appears sufficient to generate tRNA from pre-tRNA sequences that are known because they are conserved in tRNAs. Red type indicates ribozymes generated in vitro. Evolution of tRNA leads to evolution of translation systems and the genetic code. Triangles indicate the increases in biological potential associated with advances in coding [1]. Abbreviations: PTC, peptidyl transferase center; LUCA, last universal common cellular ancestor. A version of this figure was published in [1] and is reprinted here with permission.

Figure 2

The genetic code is highly structured. A 32-assignment codon-anticodon (Ac) table is shown. Codon sequences are shown on the outside (1st position, 2nd position, and 3rd wobble position). aaRS enzymes are indicated by their structural subclass (i.e., GlyRS-IIA). aaRS enzymes that edit inaccurately attached amino acids (aa) are found in columns 1 and 2. The color shading scheme reflects how amino acids were added to the code and is described in future figures. Red letters indicate very rarely used tRNAs and stop codons (strike-through) [1].

Figure 3

Evolution of the genetic code occurred mostly in columns. (A) Evolution of aaRS enzymes. Distances represent evolutionary differences. The red arrow indicates that ValRS-IA is derived from its sequence homolog GlyRS-IIA. (B) The relationship of the tRNA anticodon to the genetic code columns (Col) and rows (R). (C) The genetic code in Archaea. Grey shading indicates aaRS that possess a separate active site to edit inappropriately attached amino acids [56]. Colors highlight genetically similar aaRS enzymes demonstrating evolution primarily in columns. A version of this figure was previously published in [1] and is reprinted here with permission.

Figure 4

A proposed order of addition for amino acids (aa) to the genetic code. Amino acids appear to invade by genetic code rows. Yellow) Row 4 amino acids; Red) Row 2 amino acids; Green) Row 3 amino acids; Cyan) Row 1 amino acids and stop codons (asterisk). Leu, Ser and Arg are only scored with a single color. For simplicity, only a final, primary position in the code is scored by color.

Figure 5

The 1-amino acid code. All tRNAs are tRNA^Gly. aaRS designations are indicated, although, through multiple steps, ribozyme (RBZ) aaRS enzymes were initially probably responsible for aminoacylating tRNAs. Ac) anticodon.

Figure 6

The 4-amino acid code. Colors follow amino acids through code sectoring. Bases indicated in red type are disallowed (wobble A is very rare in Archaea) [1,14].

Figure 7

The 8-amino acid code. Columns 1, 2, and 4 sector on the 2nd and 3rd anticodon positions. Column 3 sectors on the 2nd and 1st (wobble) anticodon positions, leading to column 3 complexity.

Figure 8

The ~16-amino acid code after evolution of the EF-Tu latch. At this stage, proteins may take on sufficient complexity to replace ribozyme aaRS enzymes.

Figure 9

The standard 21-assignment genetic code (20-amino acids + stops) in Archaea. Amino acids and stop codons shaded in charcoal were late additions to the code (row 1). Column 1, row 3B (anticodon CAU) is co-occupied with Ile-IA and Met-IA.