23 The phylogenomic roots of modern biochemistry, translation, and the genetic code

Abstract

The origin and evolution of modern biochemistry is a complex problem that has puzzled scientists for almost a century. In my laboratory, we have dissected the emergence of the very early macromolecules that populated primordial cells using ideographic (historical, retrodictive) approaches. Deep evolutionary signals were retrieved from a census of molecular structures and functions in thousands of nucleic acids and millions of proteins using powerful phylogenomic methods. These clock-like signals revealed that modern biochemistry resulted from gradual coevolution and accretion of molecular parts and molecules. This was made evident in the study of aminoacyl-tRNA synthetase (aaRS) enzymes and the ribosomal ensemble. aaRSs coevolved with tRNAs, as catalytic aaRS domains and acceptor arm tRNAs accreted domains, and RNA substructures. Similarly, the ribosome originated in its central ratchet mechanism and expanded by coevolving rRNA–protein interactions (Figure 1). Remarkably, while the first biochemical functions were metabolic, the translation, the genetic code, and the ribosome appeared quite late as ‘exacting’ mechanisms that enhanced protein folding speed and flexibility, benefiting the search for new molecular functions. Our timelines reveal that translation unfolded only after the rise of viruses but prior to the appearance of diversified archaeal microbes. Remarkably, its debut coincided with the rise of nucleotide and amino acid biosynthetic pathways .