The expansion of Inosine at the wobble position of tRNAs, and its role in the evolution of proteomes.

The modification of adenosine to inosine at the first position of transfer RNA (tRNA) anticodons (I34) is widespread among bacteria and eukaryotes. In bacteria, the modification is found in tRNAArg, and is catalysed by tRNA adenosine deaminase A (TadA), a homodimeric enzyme. In eukaryotes I34 is introduced in up to eight different tRNAs by the heterodimeric adenosine deaminase acting on tRNA (ADAT). This substrate expansion significantly influenced the evolution of eukaryotic genomes in terms of codon usage and tRNA gene composition. However, the selective advantages driving this process remain unclear. Here we have studied the evolution of I34, TadA, ADAT, and their relevant codons in a large set of bacterial and eukaryotic species. We show that a functional expansion of I34 to tRNAs other than tRNAArg also occurred within bacteria, in a process likely initiated by the emergence of unmodified A34-containing tRNAs. In eukaryotes, we report on a large variability in the use of I34 in protists, in contrast to a more uniform presence in fungi, plans and animals. Our data supports that the eukaryotic expansion of I34-tRNAs was driven by the improvement brought by these tRNAs to the synthesis of proteins highly enriched in certain amino acids.