Fig. 3: Haplotype-specific peaks of mutation along the mt-genome.
From: Mitochondrial somatic mutation and selection throughout ageing
a, The average mutation frequency was calculated in 150-bp sliding windows for each strain and tissue independently. Each line represents a tissue: brain (blue), heart (red) and liver (orange). Regions with shared mutation frequency peaks in at least three mouse strains are labelled. b, The high-frequency region in the light strand origin of replication (OriL) is highlighted. For positions 5,171–5,181 the mutation frequency for the T-repeat region is calculated as the sum of mutations across this region divided by the sum of the duplex depth across positions. Each colour denotes a different strain: B6 (blue), AKR (pink), ALR (green), FVB (orange) and NZB (yellow). The average frequency in young (left, hollow points) and aged (right, filled points) mice is compared. The schematic compares the OriL structure in mice with that of macaques36. Positions with a mutation frequency >1 × 10−3 are in magenta, while other positions exibiting mutations are denoted in light blue. In the macaque OriL diagram, variant hotspots are denoted in light blue. Stars represent strains that have mutations present at a given position. c, The high-frequency region in MT-ND2 is highlighted. Colour, shape and calculation of the average mutation frequency are similar to those in b. A schematic demonstrating the sequence and codon changes that result from the indels at position 4,050: premature stop codons at codon 79 and 68 for C > CA and CA > C, respectively. The superscript denotes the position of the premature stop codon in the amino acid sequence. d, The mutation frequency for MT-tRNAArg from bp positions 9,820–9,827, which is an A-repeat region. The mutation frequency for the A-repeat region is calculated as the sum of mutations across this region divided by the sum of the duplex depth across positions. The diagram of MT-tRNAArg highlights in magenta the location of a fixed variant in NZB, which is a high heteroplasmic variant in the other mouse strains. Positions that have mutations in this region are in light blue. Positions that exceeded a mutation frequency of 1 × 10−3 were excluded from these analyses. Frequencies were normalized for sequencing depth across conditions at each position.
