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    Protein structure and evolutionary history determine sequence space topology

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    DeedsE-2005_p385.pdf (304.3Kb)
    Issue Date
    2005-01-01
    Author
    Shakhnovich, Boris E.
    Deeds, Eric J.
    Delisi, Charles
    Shakhnovich, Eugene I.
    Publisher
    Cold Spring Harbor Laboratory Press
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
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    Abstract
    Understanding the observed variability in the number of homologs of a gene is a very important unsolved problem that has broad implications for research into coevolution of structure and function, gene duplication, pseudogene formation, and possibly for emerging diseases. Here, we attempt to define and elucidate some possible causes behind the observed irregularity in sequence space. We present evidence that sequence variability and functional diversity of a gene or fold family is influenced by quantifiable characteristics of the protein structure. These characteristics reflect the structural potential for sequence plasticity, i.e., the ability to accept mutation without losing thermodynamic stability. We identify a structural feature of a protein domain—contact density—that serves as a determinant of entropy in sequence space, i.e., the ability of a protein to accept mutations without destroying the fold (also known as fold designability). We show that (log) of average gene family size exhibits statistical correlation (R2 > 0.9.) with contact density of its three-dimensional structure. We present evidence that the size of individual gene families are influenced not only by the designability of the structure, but also by evolutionary history, e.g., the amount of time the gene family was in existence. We further show that our observed statistical correlation between gene family size and contact density of the structure is valid on many levels of evolutionary divergence, i.e., not only for closely related sequence, but also for less-related fold and superfamily levels of homology.
    Description
    This is the publisher's version, also available electronically from http://genome.cshlp.org/content/15/3/385.
    URI
    http://hdl.handle.net/1808/17002
    DOI
    https://doi.org/10.1101/gr.3133605
    ISSN
    1088-9051
    Collections
    • Molecular Biosciences Scholarly Works [598]
    Citation
    Shakhnovich, Boris E.; Deeds, Eric J.; Delisi, Charles; Shakhnovich, Eugene. "Protein structure and evolutionary history determine sequence space topology." Genome Research, 15:385-392. http://www.dx.doi.org/10.1101/gr.3133605.

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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