- Caetano-Anollés G, Wang M, Caetano-Anollés D (2013) Structural phylogenomics retrodicts the origin of the genetic code and uncovers the evolutionary impact of protein flexibility. PLoS ONE 8(8): e72225. doi:10.1371/journal.pone.0072225
Tuesday, August 27, 2013
The roots of genetics lie on the peptide bond!
Proteins sustain life on our planet, from major biogeochemical cycles necessary for planetary stability to crucial signaling in brain activities important for cognition and behavior. Their misfolding results in aggregation and diseases such as Alzheimers’s or Creutzfeld-Jakob. Their challenge and deregulation causes pathogenesis and cancer. Despite of their importance, our knowledge of how this sophisticated machinery was selected to carry biological functions, the rationale for molecular change, the mysterious origin of the ‘vocabulary’ that shapes genetics (the genetic code) and the evolutionary drivers of protein structure, have yet to be uncovered. This represents important omissions in biological knowledge that need to be urgently addressed. In a remarkable breakthrough that has been published in PLoS ONE  we reveal that the fundamental molecular principle lies conspicuously not in the nucleic acids but in the protein chemical bonds. We uncover a new and more primitive code in pairs of amino acid constituents of proteins that enable protein folding and flexibility. These dipeptides were initially produced by archaic synthetases that with time transformed into a yin-yang of modern aminoacyl-tRNA synthetases, the modern safekeepers of the genetic code. The new structural code that we have uncovered appears responsible for molecular innovations. This changes the focus of molecular biology, from replicators and genetics to molecular dynamics, emergence and the chemistries of function.