Fig. 5: Functional impact of age-accumulated somatic mitochondrial mutations.
From: Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging
a, The functional profile of somatic versus germline variants. The bin width is scaled to reflect the typical number of germline and somatic variants (as sampled across 15 body sites as in Fig. 2a) in an individual. b, The age accumulation of somatic mutations by variant type in representative tissues. Variant types are colored as in a. c, The tissue-specific accumulation of deleterious mutations (defined as mutations in conserved sites, including LoF, conserved missense and conserved rRNA sites). This panel demonstrates the preferential accumulation of deleterious mutations in tissues with high cellular turnover, particularly in constantly renewing epithelial compartments. By contrast, high-energy-demanding tissues primarily accumulate mutations at hotspots within the noncoding D-loop region. Age-dependent effects (β) are assessed using linear regression. The error bars represent the 95% CI, which is based on the t-statistic of the corresponding mutation rate β and mean heteroplasmy μ estimates. Tissues in c are color-coded to represent different tissue types, following the standard GTEx conventions. Sample sizes (n, number of individuals) are marked on top of β estimates of each tissue. Detailed statistics for each estimate (slope β, 95% CI, exact P value) are provided in Supplementary Table 2. For total heteroplasmy, box plots display the median (center line), interquartile range (IQR, box limits) and whiskers (extending to 1.5× IQR); the notches provide an approximate 95% CI around the median.
