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

  • Erik A. SchultesEmail author
  • Peter T. Hraber
  • Thomas H. LaBean
Chapter
Part of the Natural Computing Series book 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.

Keywords

Molecular Evolution Sequence Space Regular Graph Hepatitis Delta Virus Neutral Network 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Erik A. Schultes
    • 1
    Email author
  • Peter T. Hraber
    • 2
  • Thomas H. LaBean
    • 1
  1. 1.Department of Computer ScienceDuke UniversityDurhamUSA
  2. 2.Theoretical Biology & Biophysics GroupLos Alamos National LaboratoryLos AlamosUSA

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