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Related Experiment Videos

Divergent evolution within protein superfolds inferred from profile-based phylogenetics.

Douglas L Theobald1, Deborah S Wuttke

  • 1Department of Chemistry and Biochemistry, UCB 215, University of Colorado, Boulder, CO 80309-0215, USA.

Journal of Molecular Biology
|November 4, 2005
PubMed
Summary

Distinguishing protein homology from convergence is challenging for similar structures with different sequences. A new phylogenetic method reveals deep evolutionary relationships, linking protein families by function, not just structure.

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Area of Science:

  • Protein structural biology
  • Computational biology
  • Evolutionary biology

Background:

  • Many proteins with dissimilar sequences adopt similar structures.
  • Differentiating homology from convergent evolution in structurally similar but sequence-divergent protein domains is a significant challenge.

Purpose of the Study:

  • To develop and apply a novel phylogenetic technique to resolve deep evolutionary relationships between protein families.
  • To investigate homology versus convergence for structurally similar protein domains lacking significant sequence similarity.

Main Methods:

  • Utilized a sequence profile-based phylogenetic technique for analyzing OB-fold, SH3, and PDZ domains with <40% sequence identity.
  • Performed an all-against-all, profile-versus-profile analysis to identify interrelationships.

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  • Inferred phylogenies using a derived relationship between E-values and evolutionary distances.

    • Main Results:

    • Discovered previously undetectable significant interrelationships between protein domains.
    • Generated phylogenies where clades strongly correlated with biological function, not structural similarity.
    • Demonstrated that functionally distinct sub-families within superfolds are homologous.

    Conclusions:

    • The developed method effectively resolves deep evolutionary relationships in the 'twilight zone' of low sequence similarity.
    • Functional correlation in phylogenies provides objective evidence for homology over convergence.
    • This approach offers a powerful tool for understanding the evolution of protein superfamilies.