Fig. 6: Somatic reversion mutations segregate in the mt-genome population.
From: Mitochondrial somatic mutation and selection throughout ageing
a, A schematic that explains somatic reversion mutations. The wild-type strain (B6) has matching nuclear and mt-genome ancestries (B6 ancestry denoted in blue). Conplastic strains are hybrids with mismatching nuclear and mt-genome ancestry. Haplotype sites are positions in the mt-genome where the conplastic mt-genome differs from the B6 mt-genome. Somatic reversion mutations refer to the re-introduction of B6 ancestral alleles at haplotype sites. b, The mutation frequency at non-haplotype sites (grey distributions) is compared with the mutation frequency at haplotype sites (green distributions or points when fewer than three haplotype sites exist). All mutations were included in the distribution of non-haplotype site mutation frequencies, including positions with a mutation frequency greater than 1 × 10−3. Haplotype site mutation frequencies were corrected for potential NUMT contamination. Mutation frequencies were normalized for sequencing depth between young and aged experimental conditions. Denoted are the adjusted empirical P value using the Benjamini–Hochberg correction. Asterisks denote the number of haplotype sites with the same P value. For AKR, ALR and FVB empirical P values for haplotype sites were calculated as the count of non-haplotype sites with a higher frequency than the haplotype site divided by the total number of non-haplotype sites (one-sided test). For NZB, the distribution of mutation frequencies for haplotype sites and non-haplotype sites was compared using the Wilcoxon rank-sum test. c, A map of the somatic reversion mutations along a linear mt-genome. Each point denotes the change in frequency with age (delta) for a somatic reversion mutation. The size of the point indicates the magnitude of delta and colour represents the conplastic strain the somatic reversion occurs in. Empirical P values were calculated as the count of sites with a delta greater (for sites with an increase in frequency with age) or less (for sites with a decrease in frequency with age) than the haplotype site delta divided by the total number of deltas (one-sided test). Fill denotes significance: not significant (NS) in hollow points and significant in filled points (adjusted empirical P value <0.02 using the Benjamini–Hochberg correction within each mt-haplotype group).
