A vocabulary of ancient peptides at the origin of folded proteins

  1. Vikram Alva
  2. Johannes Söding
  3. Andrei N Lupas  Is a corresponding author
  1. Max Planck Institute for Developmental Biology, Germany
  2. Max Planck Institute for Biophysical Chemistry, Germany

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.

Article and author information

Author details

  1. Vikram Alva

    Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. 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.
  3. 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.

Reviewing Editor

  1. John Kuriyan, Howard Hughes Medical Institute, University of California, Berkeley, United States

Version history

  1. Received: June 13, 2015
  2. Accepted: December 13, 2015
  3. Accepted Manuscript published: December 14, 2015 (version 1)
  4. Version of Record published: January 21, 2016 (version 2)

Copyright

© 2015, Alva et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Vikram Alva
  2. Johannes Söding
  3. Andrei N Lupas
(2015)
A vocabulary of ancient peptides at the origin of folded proteins
eLife 4:e09410.
https://doi.org/10.7554/eLife.09410

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https://doi.org/10.7554/eLife.09410

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