Although this sample is limited, heterogeneity in mutations found at all sites suggests that this finding is not the result of a single successful strain's sequentially acquiring mutations but rather that resistance is arising in several different strains.
Interestingly, the substitution at 4227 was missing also in the Caucasus region, including Georgian HV1a1a samples (Table 4), suggesting that this particular mutation might have been arisen within the Georgian Jewish community.
The frequency of mutation as well as back-mutation within this swarm means that beneficial and deleterious mutations are not only arising but also being removed.
As anueploidy tolerating mutations are known to arise quickly (Torres et al. Cell 2010), it is unclear whether the observed differences arise from changes in aneuploidy or mutations.
Moreover, if mtDNA mutations were to arise that were overtly sexually antagonistic in effect – benefitting females, while harming males – these would be expected to be under strong positive selection, despite their negative effects on males, as a result of maternal transmission of the mtDNA (Unckless and Herren 2009; Innocenti et al. 2011).
However, in our study, BCP mutations were seen in viruses with genotypes A, C, D, and E. These mutations are thought to arise before precore changes (25 ).
Predictive insight into how adaptation will occur -- which adaptive mutations are likely to arise and fix during selection -- is a daunting challenge.
Finally, as somatic mutations are likely to arise in the heterozygous state, the observation that variants unique to each DFTD lineage contain a high proportion of heterozygous variants provides further evidence for these sets being strongly enriched for somatic mutations.
On the basis of the varying p53 mutations in nutlin-3-selected SJSA-1 cells and the fact that they did not receive growing cell colonies under continuous nutlin-3 exposure, they suggested that the p53 mutations are likely to arise during nutlin-3 treatment.
The studies to date indicate that breast tumours arising in patients with BRCA1 mutations are different from those arising in patients with BRCA2 mutations and from non-familial cancers.
