Extended Data Fig. 10: Validation of age-associated mitochondrial mutation hotspots via targeted DNA sequencing.
From: Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging
a, Scatter plots depict the relationship between chronological age and heteroplasmy levels for five mitochondrial DNA hotspot mutations (chrM:13369, chrM:13676, chrM:152, chrM:2623, chrM:368) in human testicular tissue samples (n = 8 individuals), analyzed via targeted DNA sequencing ( > 10,000x coverage; see Methods). These hotspots were previously identified as showing significant age-related increases in heteroplasmy in the GTEx testis samples (see Fig. 3 and Supplementary Table 3). Linear regression analysis was performed to evaluate the trend of heteroplasmy change with age at each site. Hotspot chrM:9209 (potentially due to post-transcriptional RNA modification or other non-DNA mechanisms as suggested by previous findings, see Supplementary Fig. 2), was not detected among the testicular DNA samples. b, Heteroplasmy levels and corresponding read counts for the five validated hotspot mutations and associated metadata for the testicular tissue samples. Data are presented as: heteroplasmy (reference allele read count, alternative allele read count). Samples are identified by de-identified study IDs (TST-R-NN; see Methods for details). Variants identified as germline (chrM:152_T_C in samples TST-K-01, TST-B-02 and TST-F-06) are indicated with an asterisk and were excluded from the age-heteroplasmy analysis in Panel a.
