The phylogenomic roots of translation

The natural history of translation is mysterious but central to our understanding of the origin and evolution of biochemistry and life. tRNA is at the center of this biological process. Its interactions with aminoacyl-tRNA synthetase enzymes define the specificities of the genetic code and those with the ribosome their accurate biosynthetic interpretation. Here we review structural phylogenomic explorations of thousands of genomes and molecular structures that reveal a ‘metabolic-first’ origin of proteins, the early history of tRNA in interaction with cognate synthetase enzymes, the late appearance of a functional ribosome, and the co-evolutionary history of rRNA and proteins during ribosomal growth. We also discuss how the history of amino acid charging and codon specificities is embedded in tRNA and is encoded in genomes. Results uncover a hidden link between the genetic code and protein flexibility and suggest that tRNA molecules are building blocks of ribosomes and genomes. We make explicit the need to understand processes of molecular growth of macromolecules that would explain a primordial ribosome with both biocatalytic and genetic memory storage functions.