The overall contribution of such alleles to phenotypic variation is particularly high when the fitness effect distribution of deleterious mutations is leptokurtic (e.g., gamma with small shape parameter, k < 1), which appears likely (Eyre-Walker and Keightley 2007).
(e) Can one relate the fitness diffusion constant D to standard population-genetic parameters, such as the rate and effect distribution of beneficial mutations?
For example, with a shape parameter of k = 0.2 (as previously estimated from the sex-averaged fitness effect distribution of nonsynonymous mutations in humans; Keightley and Eyre-Walker 2007; Boyko et al.
We assume that σ is gamma distributed with mean of 0.012 and a shape parameter of 2. The choice of a gamma distribution is based on a virological study showing that the distribution of beneficial mutation effects appear to be gamma distributed (Sanjuán et al., 2004).
What is the distribution of mutation effects on the adapters?
One example of the distribution of mutation effects and the corresponding fitness variation caused by mutations we adopt is shown in Figure 1.
Other measures of dimensionality based on the distribution of mutation effects in Fisher's geometric model have been proposed [ 11], but they are dependent on assumptions of made on how mutations affect phenotypes [ 18, 35] and have failed to be informative in our system (data not shown).
As for the third assumption, we do not yet have a good understanding of the distribution of deleterious mutation effects due to their complexity.
We found that the distribution of secondary mutation effects in the dps-deleted strain was significantly different from that of the reference strain (D = 0.633, P < 0.001).
Whether a secondary mutation will displace a previously spreading one depends, among other factors, on the frequency reached by the first mutation when the second one arises, and on their relative selective values, which in the last term are determined by the distribution of beneficial mutation effects.
