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dc.contributor.authorShakhnovich, Boris
dc.contributor.authorDeeds, Eric
dc.contributor.authorDelisi, Charles
dc.contributor.authorShakhnovich, Eugene
dc.date.accessioned2019-10-11T12:29:30Z
dc.date.issued2005
dc.identifier.citationShakhnovich, B. E. 2005. “Protein Structure and Evolutionary History Determine Sequence Space Topology.” Genome Research15 (3): 385–92. https://doi.org/10.1101/gr.3133605.
dc.identifier.issn1088-9051
dc.identifier.issn1549-5469
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41534487*
dc.description.abstractUnderstanding 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 ill 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 (R-2 > 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 oil many levels of evolutionary divergence, i.e., [lot only for closely related sequence, but also for less-related fold and superfamily levels of homology.
dc.language.isoen_US
dc.publisherCold Spring Harbor Laboratory Press
dash.licenseLAA
dc.titleProtein structure and evolutionary history determine sequence space topology
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalGenome Research
dash.depositing.authorShakhnovich, Eugene Isaacovitch::f6c3b099a5c771576073eb9a31658d2e::600
dc.date.available2019-10-11T12:29:30Z
dash.workflow.comments1Science Serial ID 43670
dc.identifier.doi10.1101/gr.3133605
dash.source.volume15;3
dash.source.page385


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