1. Biochemistry and Chemical Biology
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Random-sequence genetic oligomer pools display an innate potential for ligation and recombination

  1. Hannes Mutschler  Is a corresponding author
  2. Alexander I Taylor
  3. Benjamin T Porebski
  4. Alice Lightowlers
  5. Gillian Houlihan
  6. Mikhail Abramov
  7. Piet Herdewijn
  8. Philipp Holliger  Is a corresponding author
  1. MRC Laboratory of Molecular Biology, United Kingdom
  2. Katholieke Universiteit Leuven, Belgium
Research Article
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Cite this article as: eLife 2018;7:e43022 doi: 10.7554/eLife.43022

Abstract

Recombination, the exchange of information between different genetic polymer strands, is of fundamental importance in biology for genome maintenance and genetic diversification mediated by dedicated recombinase enzymes. Here, we describe a pervasive non-enzymatic capacity for recombination (and ligation) in random-sequence genetic oligomer pools. Specifically, we examine random and semi-random eicosamer (N20) pools of RNA, DNA and the unnatural genetic polymers ANA (arabino-), HNA (hexitol-) and AtNA (altritol-nucleic acids). While DNA, ANA and HNA pools proved inert, RNA and AtNA pools displayed diverse modes of spontaneous intermolecular recombination, connecting recombination mechanistically to the vicinal ring cis-diol configuration shared by RNA and AtNA. Thus, the chemical constitution that renders both susceptible to hydrolysis emerges as the fundamental determinant of an innate capacity for recombination, which is shown to enable a concomitant increase in compositional, informational and structural pool complexity and hence evolutionary potential.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for: Figure 1, Figure 1-supplement 1, Figure 2, Figure 2-supplement 1, Figure 4, Figure 4-supplement 2, Figure 4-supplement 3, Figure 5, Figure 5-supplement 1, Figure 6 and Figure 6-supplement 2. Further source files are shell scripts for the motif search, extraction of secondary structure frequencies and size distributions and python scripts for the generation of random sequences using position-specific nucleotide frequencies and the simulations of the population level Shannon Index at different cleavage / ligation rates are available online (see Source Code Files 1-5).

The following data sets were generated

Article and author information

Author details

  1. Hannes Mutschler

    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    For correspondence
    mutschler@biochem.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8005-1657
  2. Alexander I Taylor

    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7684-1437
  3. Benjamin T Porebski

    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Alice Lightowlers

    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Gillian Houlihan

    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Mikhail Abramov

    REGA Institute, Katholieke Universiteit Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  7. Piet Herdewijn

    REGA Institute, Katholieke Universiteit Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3589-8503
  8. Philipp Holliger

    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    For correspondence
    ph1@mrc-lmb.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3440-9854

Funding

Medical Research Council (MC_U105178804)

  • Alexander I Taylor
  • Benjamin T Porebski
  • Gillian Houlihan
  • Philipp Holliger

Federation of European Biochemical Societies (FEBS Long-Term Fellowship)

  • Hannes Mutschler

KU Leuven (OT/1414/128)

  • Mikhail Abramov
  • Piet Herdewijn

FWO Vlaanderen (G078014N)

  • Mikhail Abramov
  • Piet Herdewijn

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Ulrich Muller, UCSD, United States

Publication history

  1. Received: October 21, 2018
  2. Accepted: November 16, 2018
  3. Accepted Manuscript published: November 21, 2018 (version 1)
  4. Version of Record published: December 11, 2018 (version 2)

Copyright

© 2018, Mutschler 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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