title: A vocabulary of ancient peptides at the origin of folded proteins.
abstract: The seemingly limitless diversity of proteins in nature arose from only a few thousand domain prototypes, but the origin of these themselves has remained unclear. We are pursuing the hypothesis that they arose by fusion and accretion from an ancestral set of peptides active as co-factors in RNA-dependent replication and catalysis. Should this be true, contemporary domains may still contain vestiges of such peptides, which could be reconstructed by a comparative approach in the same way in which ancient vocabularies have been reconstructed by the comparative study of modern languages. To test this, we compared domains representative of known folds and identified 40 fragments whose similarity is indicative of common descent, yet which occur in domains currently not thought to be homologous. These fragments are widespread in the most ancient folds and enriched for iron-sulfur- and nucleic acid-binding. We propose that they represent the observable remnants of a primordial RNA-peptide world.
authors.affiliation: Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Vikram
authors.initials: V
authors.lastname: Alva
authors.affiliation: Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Johannes
authors.identifier: http://orcid.org/0000-0001-9642-8244
authors.initials: J
authors.lastname: Söding
authors.affiliation: Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Andrei N
authors.identifier: http://orcid.org/0000-0002-1959-4836
authors.initials: AN
authors.lastname: Lupas
mesh_terms: D019295:Computational Biology; D019143:Evolution, Molecular; D014644:Genetic Variation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*
chemical_list: D011506:Proteins
keywords: LUCA; RNA-peptide world; ancient peptides; biochemistry; biophysics; domain evolution; none; protein evolution; structural biology