The proliferation of cells that results from stimulation by endocrine, autocrine and paracrine growth factors increases risk for mutation [ 134].
We have proposed that declining stem and progenitor cell fitness, whether due to aging or other insults, should increase selection for mutations (or epimutations) that are adaptive (i.e. that improve fitness) [ 10, 11, 16].
On the other hand, moderate and strong selection caused a quick reduction of the MSE from youngest mutations to mutations arising in generations 920 to 939, thus resulting in a progressive increase for older mutations.
The focus of this study is mature dinucleotide microsatellites in the human genome, which are expected to be at increased risk for mutation.
TS-PTDH contains 12 mutations that result in considerably increased thermostability with minimal change in activity, and four additional mutations that increase its activity (for mutations, see Materials and Methods).
Somewhat misaligned nucleotides might occur and further increase the probability for mutations.
In particular, estrogens are believed to contribute to tumor growth by promoting the proliferation of cells with existing mutations or perhaps by increasing the opportunity for mutations [ 1].
An alternative approach that has been used is to amplify clones of cells, derived from a single cell, to increase the sensitivity for mutation detection by increasing the amount of starting material (36, 68).
This barcoding has the potential to increase the detection accuracy for mutations at 1 % fraction or lower by removing low level false positives [ 8, 12, 13].
Evolutionary stress can drive selection for increased mutation rates: mutator bacterial strains are more antibiotic resistant than non-mutator strains, and thus have a clear selective advantage, potentially leading to an increase in the overall mutation rate within a population [13].
