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No Molecule Is an Island: Molecular Evolution and the Study of Sequence Space

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Book cover Algorithmic Bioprocesses

Part of the book series: Natural Computing Series ((NCS))

Abstract

Our knowledge of nucleic acid and protein structure comes almost exclusively from biological sequences isolated from nature. The ability to synthesize arbitrary sequences of DNA, RNA, and protein in vitro gives us experimental access to the much larger space of sequence possibilities that have not been instantiated in the course of evolution. In principle, this technology promises to both broaden and deepen our understanding of macromolecules, their evolution, and our ability to engineer new and complex functionality. Yet, it has long been assumed that the large number of sequence possibilities and the complexity of the sequence-to-structure relationship preempts any systematic analysis of sequence space. Here, we review recent efforts demonstrating that, with judicious employment of both formal and empirical constraints, it is possible to exploit intrinsic symmetries and correlations in sequence space, enabling coordination, projection, and navigation of the sea of sequence possibilities. These constraints not only make it possible to map the distributions of evolved sequences in the context of sequence space, but they also permit properties intrinsic to sequence space to be mapped by sampling tractable numbers of randomly generated sequences. Such maps suggest entirely new ways of looking at evolution, define new classes of experiments using randomly generated sequences and hold deep implications for the origin and evolution of macromolecular systems. We call this promising new direction sequenomics—the systematic study of sequence space.

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Author information

Authors and Affiliations

  1. Department of Computer Science, Duke University, Durham, NC, 27708, USA

    Erik A. Schultes & Thomas H. LaBean

  2. Theoretical Biology & Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA

    Peter T. Hraber

Authors
  1. Erik A. Schultes
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  2. Peter T. Hraber
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  3. Thomas H. LaBean
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Corresponding author

Correspondence to Erik A. Schultes .

Editor information

Editors and Affiliations

  1. Dept. Computer Science, University of British Columbia, Main Mall 201-2366, Vancouver, V6T 1Z4, Canada

    Anne Condon

  2. Dept. Applied Mathematics, Weizmann Institute of Science, Rehovot, 76100, Israel

    David Harel

  3. Leiden Inst. Advanced Computer Science, Leiden University, Niels Bohrweg 1, Leiden, 2333 CA, Netherlands

    Joost N. Kok

  4. Turku Centre for Computer Science, Lemminkaisenkatu 14 A, Turku, 20520, Finland

    Arto Salomaa

  5. Computer Science, Computation,, California Inst. of Technology, Pasadena, 91125, U.S.A.

    Erik Winfree

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Schultes, E.A., Hraber, P.T., LaBean, T.H. (2009). No Molecule Is an Island: Molecular Evolution and the Study of Sequence Space. In: Condon, A., Harel, D., Kok, J., Salomaa, A., Winfree, E. (eds) Algorithmic Bioprocesses. Natural Computing Series. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-88869-7_34

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  • DOI: https://doi.org/10.1007/978-3-540-88869-7_34

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