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The stepwise mutation model: an experimental evaluation utilizing hemoglobin variants.

P A Fuerst1, R E Ferrell

  • 1Center for Demographic and Population Genetics, University of Texas Health Science Center, P. O. Box 20334, Houston Texas 77025.

Genetics
|January 1, 1980
PubMed
Summary
This summary is machine-generated.

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Electrophoretic mobility of hemoglobin variants is mainly determined by net molecular charge. However, deviations suggest that the infinite-allele or mixed models may better explain genetic variability than the stepwise mutation model.

Area of Science:

  • Molecular Biology
  • Population Genetics
  • Biochemistry

Background:

  • The stepwise mutation model explains genetic variability observed through electrophoresis.
  • This model assumes electrophoretic mobility is primarily dictated by net molecular charge.
  • Previous research has questioned this assumption, necessitating direct testing.

Purpose of the Study:

  • To empirically test the assumption that net molecular charge solely determines electrophoretic mobility.
  • To evaluate the suitability of the stepwise mutation model versus alternative models for analyzing electrophoretic data.

Main Methods:

  • Starch gel electrophoresis was used to analyze 27 human and 26 nonhuman hemoglobin variants with known sequences.
  • Electrophoretic mobility was compared with net charge calculated from amino acid composition.

Related Experiment Videos

  • Deviations from predicted mobility were analyzed in relation to amino acid divergence.

    • Main Results:

    • 60-70% of hemoglobins showed mobilities predictable by net charge alone.
    • A significant portion (30-40%) exhibited mobilities influenced by factors beyond net charge, likely tertiary structure changes.
    • Increased amino acid divergence correlated with greater deviations in nonhuman hemoglobins.

    Conclusions:

    • Net electrostatic charge is the primary determinant of electrophoretic mobility for hemoglobins under tested conditions.
    • Observed deviations indicate that the stepwise mutation model may be insufficient for analyzing much electrophoretic data.
    • The infinite-allele or mixed models may offer more appropriate frameworks for population genetic analyses of electrophoretic data.