In this case, for the mutator pathway, the mutator mutation is allowed to occur anywhere up to (but not including) the point where D oncogenic mutations have occurred, and these D possible time intervals are summed.
Reverse mutation was allowed.
Under this assumption, for which each somatic mutation only happen once in the evolutionary history and not reverse mutation are allowed, subclonal cells can be identified and their prevalence estimated.
If a haplotype representing the first mutant occurring in one of the first k−1 marker populations had t a < 1, this mutation was allowed to have an initial frequency greater than q0, the initial frequency of the corresponding wild-type haplotype being decreased accordingly.
Most mutations that were predicted to disrupt the secondary structures fail to replicate, while compensatory mutations were allowed replication to resume.
Mutations were allowed in all historical generations for all loci with a mutation rate of 1.25×10−3 per locus, per generation, and per animal.
At the highest temperature of 0.6, the reverse polymerizing organisms are unable to establish themselves the same as when mutations were allowed, implying that this inability to compete with forward polymerizing organisms during exponential growth is a consequence of the spontaneous hydrolysis penalty and is not affected by the presence or absence of mutations in the system.
We noted that the results of this last experiment seemed to indicate that, when mutations were allowed, their might be a temperature regime in which there is a transition between an equilibrium of organisms containing forward and reverse polymerases and a complete dominance by organisms containing the forward polymerase.
We noticed that the decline in population of reverse polymerizing organisms when starting from a full environment is roughly exponential, so we plotted the natural log of this number against simulation time in figures 7, A & B for simulations where mutations were allowed in the system or where they were prohibited, respectively.
The alignment of sequences was unnecessary because only point mutations were allowed to occur during a simulation.
