Figure 6. Mitochondrial DNA point mutation during mouse development.

Expansion of mtDNA point mutations during heart tissue development from in silico wild-type (A), POLG^+/mut (B) and POLG^mut/mut mice (C) population (n = 1,100). (A) The square symbols show examples of point mutation trajectory from two different mice, one of which suffers from a rare point mutation early in the development, resulting in the amplification of the mutation frequency in subsequent cell divisions. (B) Like in the wild-type cohort, de-novo point mutations generated in the POLG^+/mut mice during the early cell divisions can accumulate very quickly, resulting in a high mutation load in the cells at birth. (C) Since the error rate of mtDNA replication in POLG^mut/mut is much higher than the wild-type mtDNA replication, a significant proportion of the population (>75%) harbors mtDNA mutations at an early stage of development (before the 10^th cell division). As a consequence, the resulting mutation load in the tissue is significantly higher than that in the wild-type tissues at birth.