Fig. 4: Postzygotic mtDNA variants toward homoplasmy in aged cells.
From: Mitochondrial DNA mosaicism in normal human somatic cells
a, Linear correlation between the average PZsimple mutation count and age across 31 individuals. The gray line and the shaded area represent the regression line and its 95% confidence interval. One individual aged 0 was not included in the regression. Vertical lines indicate the range of PZsimple mutation counts per clone in an individual. b, Proportions of clones with maximum clone-VAFs across 31 individuals (individual ages indicated in parentheses). Individuals are sorted by tissues, then by age, in ascending order. c, Bar plots of SVAF for each clone in two individuals, DB8 (93 years old; top) and HC10 (37 years old; bottom), with developmental phylogenies. Bar plots include up to the top three clone-VAF PZsimple mutations. Pie charts categorize clones based on SVAF. d, Linear correlation between average SVAF and total mitotic turnovers across 31 individuals. The total number of mitotic turnovers was calculated using the rates estimated by HetFE variants for each tissue type. The gray line and shaded area represent the regression line and its 95% confidence interval. One individual aged 0 was not included in the regression. Vertical lines indicate the range of SVAF per clone in an individual. (a,b,d, Clones with high UV exposure were excluded to remove UV radiation’s impact. Pearson’s correlation coefficient and P value are provided. Two-sided Pearson’s correlation.) e, Comparison of clone proportions with maximum clone-VAFs of PZsimple mutations in fibroblast clones with low and high UV-derived nDNA mutation burdens in three donors. f, Estimated mtDNA mutation rate in 31 individuals under mitotic and homeostatic turnover models (individual ages indicated in parentheses). Error bars represent the range of 50 simulated results with the lowest MSEs of 10,000 simulations per individual, with circles representing average values.
