A vocabulary of ancient peptides at the origin of folded proteins

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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.

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Vikram Alva

Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany

Competing interests
The authors declare that no competing interests exist.
Johannes Söding

Research Group for Quantitative and Computational Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

Competing interests
The authors declare that no competing interests exist.
Andrei N Lupas

Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany

For correspondence
andrei.lupas@tuebingen.mpg.de

Competing interests
The authors declare that no competing interests exist.

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