PMC

(a) Circos diagrams of mutations throughout the genome showing the genomic distributions of germline (blue) and somatic (red) mutations for which location data was available in humans (left) and mice (right). (b) Barplots of mutation types, including flanking bases, as a percentage of total mutations. (c) Principal component analysis of the data from b reveals distinct patterns of mutation that differ between germline and soma, as well as between mice and humans. Each point represents an individual offspring (in the case of germline mutations) or an individual cell (in the case of somatic mutations).

(a) Schematic representations of de novo germline (left) and somatic (right) mutation identification after whole genome sequencing. Germline mutations were determined by calling SNVs in DNA from offspring not present in parental DNA, while somatic mutations were identified as those present in single amplified fibroblasts or unamplified fibroblast clones, but not present in bulk DNA from the same cell populations. (b) Germline and somatic mutation frequencies in human and mouse before and after correction for the number of cell divisions. Horizontal bars indicate median ±1s.d. All groups were significantly different from all other groups (Wilcoxon test; mouse germline versus mouse somatic frequency: P=0.0016; mouse germline versus human germline frequency: P=1.6e-5; mouse germline versus human somatic frequency: P=4.6e-5; mouse somatic versus human germline frequency: P=0.00032; mouse somatic versus human somatic frequency: P=0.0013; human germline versus human somatic frequency: P=3.09e-6; mouse germline versus mouse somatic rate: P=0.0016; mouse germline versus human germline rate: P=0.0022; mouse germline versus human somatic rate: P=4.57e-5; mouse somatic versus human germline rate: P=0.00032; mouse somatic versus human somatic rate: P=0.00067; human germline versus human somatic rate: P=3.09e-6). (c) Number of somatic mitoses necessary to equalize the somatic and germline mutation rates in humans and mice, assuming the germline mutation rates are correct. The solid lines indicated the predicted somatic mutation rate for the given number of mitoses; the values used in the paper are indicated with large points. The dashed lines indicate the germline mutation rates. The human fibroblasts, given the somatic mutation frequency we observed, would have had to undergo more than 8,000 mitoses for the somatic mutation rate to be equal to the germline mutation rate. The mouse fibroblasts would have had to undergo over 3,000 mitoses to have the same mutation rate per mitosis as the germline cells.