For deletion or insertion types of mutations, we used the average of mA% of the first five different waves from the beginning of mutations (Figure S1).
DOI: http://dx.doi.org/10.7554/eLife.11282.007 To measure the rate at which the virus population accumulates mutations, we calculated the average distance of each sample from the approximate founder sequence in 300 bp windows.
Among 6 classes of transition and transversion mutations, we observed an average of 2.39% and 4.87% increases in T A > G C (P = 8.46e-16) and C G > G C (P < 2.2e-16 2.2e-16ersion, respectransversionetastasis-specific mutations, which may be caused by micrespectivelyt seeding or effects of chemotherapy [ 13].
From the above density of mutations we have calculated an average number of 1404 mutations per line, the complete TILL er collection providing a total of 5.2 million mutations.
In order to differentiate sequencing errors from mutations, we used three thresholds to filter out unreliable mutation results: (1) we required at least five reads for each mutation; (2) average quality of each mutation had to be higher than 20; (3) there had to be at least one pair of mate-pair reads to support.
Because approximately 3000 clones are needed to cover 1.5 mutations on average, we harvested ∼10,000 E. coli colonies for the sublibrary, which we named sublibrary 9.1.
We found that Tibetan highlanders carried 0.19 (±0.39) tRNA pathogenic mutations in average, significantly more than those in controls (0.13 ± 0.34, Mann–Whitney U test, P = 0.028).
Given a mean lifetime to fixation of 2.9 years as shown in Figure 3C, we conclude that the population contains at least three simultaneous adaptive mutations on average.
In contrast, the mutator alleles produced ∼2- to 10-fold more mutations on average.
Both diseases showed overall low somatic mutation rates (on average 4.6 mutations per exome); mutations identified in pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma were seen in pathways important for transcription, intracellular signaling and cellular organization.
