Abstract
The twenty amino acids in the standard genetic code were fixed prior to the last universal common ancestor (LUCA). Factors that guided this selection included establishment of pathways for their metabolic synthesis and the concomitant fixation of substrate specificities in the emerging aminoacyl-tRNA synthetases (aaRSs). In this conceptual paper, we propose that the chemical reactivity of some amino acid side chains (e.g., lysine, cysteine, homocysteine, ornithine, homoserine, and selenocysteine) delayed or prohibited the emergence of the corresponding aaRSs and helped define the amino acids in the standard genetic code. We also consider the possibility that amino acid chemistry delayed the emergence of the glutaminyl- and asparaginyl-tRNA synthetases, neither of which are ubiquitous in extant organisms. We argue that fundamental chemical principles played critical roles in fixation of some aspects of the genetic code pre- and post-LUCA.
Highlights
The Central Dogma, including machinery for mRNA-guided, ribosomal protein translation, had already been defined at the time of the last universal common ancestor (LUCA) [1,2]
We propose that this difference was sufficient to favor ornithine lactam formation over Orn-tRNALys biosynthesis, allowing lysine to claim a spot in the modern genetic code
In the two preceding sections, we argued that the nucleophilicity of ornithine, homocysteine, homoserine, and selenocysteine directly impacted the exclusion of these amino acids from the standard genetic code
Summary
The Central Dogma, including machinery for mRNA-guided, ribosomal protein translation, had already been defined at the time of the last universal common ancestor (LUCA) [1,2]. LUCA contained two non-discriminating (ND) aaRSs: ND-aspartyl- and ND-glutamyl-tRNA synthetase [8]. We will focus on the emergence of six aaRSs—all of which were either absent, non-discriminating, or duplicated in the most likely LUCA—namely the glutamylaspartyl-, glutaminyl-, asparaginyl-, cysteinyl-, and lysyl-tRNA synthetases (ND-GluRS, ND-AspRS, GlnRS, AsnRS, CysRS, and LysRS). AspRS have been omitted from this figure because non-discriminating variants of these enzymes existed at the time of LUCA and were tied to the delayed emergence of GlnRS and AsnRS [11]. We will refer to non-standard amino acids using their assigned three letter codes as follows: selenocysteine (Sec), ornithine (Orn), homocysteine (Hcy), and pyrrolysine (Pyl)
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