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On three methods for estimating mutation rates indirectly.

E Pollak

    American Journal of Human Genetics
    |February 1, 1986
    PubMed
    Summary
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    Estimating mutation rates (mu) relies on models assuming allele extinction. In growing populations, neutral alleles face rapid extinction, influencing mutation rate calculations and confidence intervals.

    Area of Science:

    • Population Genetics
    • Evolutionary Biology
    • Quantitative Genetics

    Background:

    • Established methods by Kimura and Ohta, Nei, and Rothman and Adams exist for estimating mutation rates (mu).
    • These methods commonly assume the ultimate extinction of all alleles.
    • The behavior of neutral alleles in growing populations is crucial for understanding extinction dynamics.

    Purpose of the Study:

    • To evaluate the applicability of existing mutation rate estimation methods.
    • To investigate the impact of population growth on allele extinction dynamics.
    • To refine mutation rate estimation and establish confidence intervals.

    Main Methods:

    • Analysis of existing mutation rate estimation models (Kimura and Ohta, Nei, Rothman and Adams).

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  • Application of branching process approximations for stochastic processes in growing populations.
  • Computation of conservative high and low estimates for mutation rates and their standard deviation.

    • Main Results:

    • All three reviewed methods are most effective for rare alleles.
    • Conditioning on ultimate extinction in growing populations allows approximation by branching processes with a mean offspring number less than 1.
    • Low mean extinction times (t0) in simulations are linked to rapid population growth and reduced effective population size.

    Conclusions:

    • Mutation rate estimation methods are best suited for rare alleles and assume extinction.
    • Population growth significantly accelerates allele extinction, impacting rate estimations.
    • Calculated confidence intervals for mutation rates encompass previously reported estimates, validating the refined approach.