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F. M. PHELPS, A Unifying Model for the Substitutional Genetic Load, Mathematical Medicine and Biology: A Journal of the IMA, Volume 8, Issue 1, 1991, Pages 31–56, https://doi.org/10.1093/imammb/8.1.31
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Abstract
In this paper, a general deterministic model for gene substitution at all segregating loci is derived. The results of a rigorous mathematical analysis of the equations are stated and found to be consistent with results derived by making typical simplifying assumptions. All previous deterministic calculations of possible rates of gene substitution and the ‘substitutional genetic load’ are shown to be special cases of the model. New expressions for the substitutional genetic load and rate of substitution in hard selection with cth-order epistasis are given. In addition, the concept of ‘threshold selection’ is generalized to less extreme ‘rank selection”, and formulae for the relationship between the substitution rate and the selection coefficient are given. The ‘load argument’ for the neutral theory is reviewed in light of the new findings and strongly rejected. Several other areas of disagreement, such as the effect of population dynamics and competition on the substitutional genetic load, are sorted out using the model. Some remarks regarding experimental input are made.