Mutation rate variability is a key theme in current discussions of the need for an extended evolutionary synthesis [14], [15] under the name of "the evolution of evolvability", the tantalizingly recursive possibility that the ability of organisms to evolve is itself a trait, or spectrum of traits, under evolutionary control [16] [19].
As a result, patterns of polymorphism at these loci are likely to reflect not only genome-wide processes such as demographic history but also local, locus-specific effects of selection, mutation rate variability and Hill-Robertson [ 6, 7] effects.
Mutation rate also influences genetic variability.
We obtained similar results when we repeated these experiments across a variety of parameter values, confirming the robustness of our model to the number of transient cell divisions before terminal differentiation, mutation rate, symmetric division trait variability, and maximum neoplasm size (see Supplementary Text, Figs. S1 S3, Table S1).
While the precise time it takes for tumor-propagating cells to dominate the tumor varies due to model parameters, it takes less time under high mutation rates, high symmetric division rate variability, large neoplasm size, and fewer transient cell stages (Table S2).
Due to the high genetic variability and mutation rate of HIV, vaccines are not available to curb the HIV infection [2].
The results of the evolutionary rates were consistent with previous findings demonstrating that human SNP (single-nucleotide polymorphism) variability and mutation rate are higher in regions of high recombination [ 14].
The presence of an error threshold in viruses is a consequence of a trade-off between the maximization of variability (genomic mutation rate) and the maintenance of molecule integrity (genomic size).
Given that imperfection strongly correlates with recombination rate but shows significant cross-population correlation even after corrections for recombination rate, it is likely that these regional correlations reflect a combination of regional variation in recombination rate and regional variability in mutation rate.
We tested this with our model, and as expected, we found that the probability for symmetric division could not evolve under low mutation rates and trait variability (Fig. S2).
Mitochondrial DNA is the most appropriate marker in this instance as the mutation rate is rapid enough to provide variability over the time scales in question, and recombination is very unusual, enabling straightforward interpretation of the patterns observed [ 21].
