Figure 1.

mtDNA positions harboring de novo cancer mutations preferentially occur in deep branches of human phylogenetic tree. Using maximum parsimony to assign mutations to branches of the human mtDNA phylogenetic tree, a maximal depth of fixation (MDF) value was calculated for 3328 mtDNA positions that vary in a compendium of coding region sequences (for description of the compendium, see text). The distributions of MDF values were compared to reported mutations in cancer data sets (A) and to noncancer positions, i.e., positions that were mutated only in the human compendium (B). To control for difference in the variability levels of the two types of positions, a sample of noncancer positions was used, sampled such that their variability levels precisely matched the variability level of the cancer positions. For estimating the statistical significant of the bias toward higher MDF values in cancer positions compared with noncancer positions (\, {\bar p}), the P-value estimate from a one-sided Mann-Whitney U-test was averaged over 1000 independently generated variability matched samples. To ensure the repeated sampling is meaningful, highly variable positions (assigned to 13 or more inner nodes) were ignored, since these could not be matched between the cancer and noncancer sets.