Fig. 5

Putative NCR multimers are Polg^D181A-specific and accumulate with age in a highly brain region-specific manner. a Dot plot illustrating the age-dependent increase in the load of VLRDs in Polg^D181A mice across the investigated brain regions (as indicated by the colour legend). All samples have been normalised to the sample with the lowest number of detected variants. b Cumulative percentage of 5′ position of VLRDs (i.e. start position of the putative multimeric sequence) summed across brain regions for WT (grey) and Polg^D181A (red) for 10- (dotted line), 50- (dashed line), and 80-week-old (full line) mice. c Mean number of discordant reads as extracted by samtools at 10, 50, and 80 weeks for WT (grey) and Polg^D181A (red) and standard deviation is indicated. p values of two-sided t tests are shown. d Summed analysis of mtDNA breakpoints of VLRDs from Polg^D181A mice in the NCR and surrounding region. 5′ (purple) and 3′ (dark turquoise) breakpoints are summed at each position across all brain regions at either 50 (left) or 80 (right) weeks old, and smooth conditional means are plotted. The lower panel shows the phastCons conservation score via the UCSC genome browser in the same region. p values of two-sided t tests are shown. e Boxplot showing the shortest average distance to a direct repeat of all Polg^D181A VLRDs separated by VLRD 5′ position into < 15 kb (light blue) or > 15 kb (dark blue). p values of two-sided t tests are shown. f Boxplot showing the Needle identity score of WT and Polg^D181A-derived VLRDs pooled across ages and brain regions examined split into VLRDs with 3′ position < 15 kb (light blue) and > 15 kb (dark blue). p values of two-sided Wilcoxon tests are shown