We iterated our calculations on multiple published mutation rates (see Methods), as well as an empirical observation for mutation rate derived from the known divergence time (16 years, S. Zinder, pers. comm).
This genetic variability can be attributed to the often higher mutation rates, multiple selective hurdles, variable micro-environments, and increased numbers of cell generations that characterize cancers.
Multiple factors (e.g., mutation rates, effective vs. census population sizes, and percentage of immigrants successfully breeding) made it difficult to convert estimates based on population genetics to absolute numbers of immigrant individuals.
The dependence of the number of species and ecosystem structure on mutation rate is in line with Takeuchi and Hogeweg (2008): Although for lower mutation rates multiple lineages coexist in the field, when mutation rate is sufficiently high (μ ≥ 0.014 ) only one quasispecies is present.
Other studies have used strains with extremely high mutation rates due to multiple mutator alleles (Larrea et al. 2010).
In contrast to the one-by-one model of clonal interference, which predicts decelerated adaptation rates and transient levels of genetic variation at large population size (N) and high beneficial mutation rate (μb), the multiple mutation model predicts that the both the speed of adaptation and variation in fitness increase logarithmically with N and with μb.
As a consequence of a separate experiment that was designed to determine the basal mutation rates of multiple organisms, including A. tumefaciens C58-CU, we discovered a second deletion event that was qualitatively similar to the first.
We note that besides the multiple pathways considered above, Little and Wright [ 11], Little et al. [ 12] and Little [ 13] have also included mixture type of multiple pathways; however, because the mutation rates are very small, the chance of mixture type of pathways will be extremely small in which case the Little model is equivalent to the model in Section 3.
In mutagenicity testing, critical mutation frequencies are defined in terms of multiples of SDs of background mutation rates (Venitt and Parry 1984).
It concludes that most cancers exhibit a mutator phenotype as normal mutation rates are insufficient to account for the multiple mutations observed in human tumors.
