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Related Experiment Videos

Dobzhansky-Muller incompatibilities in protein evolution.

Alexey S Kondrashov1, Shamil Sunyaev, Fyodor A Kondrashov

  • 1National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20894, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 31, 2002
PubMed
Summary
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Approximately 10% of protein differences between species are compensated pathogenic deviations (CPDs). Proteins evolve along fitness ridges, navigating these CPDs through rapid, positively selected substitutions.

Area of Science:

  • Evolutionary biology
  • Molecular evolution
  • Protein evolution

Background:

  • Protein sequence evolution involves accumulating genetic changes.
  • Human pathogenic mutations provide insights into protein function and constraints.
  • Understanding evolutionary pathways is crucial for predicting protein adaptation.

Purpose of the Study:

  • To investigate the relationship between human pathogenic mutations and evolutionary substitutions in proteins.
  • To characterize the concept of compensated pathogenic deviations (CPDs) in protein evolution.
  • To elucidate the mechanisms and pathways of protein evolution along fitness ridges.

Main Methods:

  • Comparative analysis of human pathogenic missense mutations and evolutionary amino acid substitutions in 32 proteins.

Related Experiment Videos

  • Identification and quantification of compensated pathogenic deviations (CPDs).
  • Analysis of protein structures and co-occurrence data to identify compensatory substitutions.

    • Main Results:

    • Approximately 10% of nonhuman protein deviations from human orthologs are CPDs.
    • CPDs, along with compensatory changes, form Dobzhansky-Muller incompatibilities, visualized as corners on fitness ridges.
    • Proteins evolve along fitness ridges with approximately 10 steps between corners, suggesting rapid, positively selected substitutions.

    Conclusions:

    • Protein evolution proceeds along fitness ridges, driven by rapid successive substitutions that overcome incompatibilities.
    • Compensatory changes, often within the same protein, are crucial for the functional viability of proteins with CPDs.
    • Fitness landscapes guide protein evolution, with CPDs representing key evolutionary transitions.