In this way, mutator mutations are effectively removed from the tumour population as a result of their being outcompeted by the most aggressive clones.
How many of our observed mutations are effectively neutral is highly dependent on the effective population size, which is probably very high in the bulk competition experiment (cf., e.g., Skelly et al. 2009, who estimate Ne ≈ 2.6 × 10).
In contrast, many more mutations are effectively neutral in D. miranda, but the average effect of the mutations incorporated would be larger.
In a species with a larger effective population size, a smaller fraction of mutations is effectively neutral, and one might expect such a species to be better adapted since more advantageous mutations will fix [ 18].
Approximately 25% of mutations are effectively neutral, approximately 25% are mildly deleterious, and 50% are strongly deleterious.
As expected, a nearly constant rate of mutation accumulation is observed only in cases in which the majority of mutations are effectively neutral.
That is because mutations are effectively neutral if Ne s < 1, i.e. their fate is mostly governed by genetic drift and not selection [ 18].
Genes with the lowest estimates of Fop may have low equilibrium optimal levels of codon bias, and therefore additional preferred mutations are effectively neutral.
For example, not all synonymous mutations are effectively neutral [ 64, 85, 86], gene order is not random [ 87], back-mutations and compensatory mutations can be important [ 76- 78] and epistatic interactions between mutations are frequent [ 88- 92].
