Figure 3. Stochastic determinants of age-dependent dynamics in the observed mtDNA point mutation frequency.

Heart tissue simulations provided the distribution of mutation frequency among 1,100 in-silico wild type mice. (A, B) The percentiles and probability distribution functions of the mutation frequency arising from the intrinsic stochasticity of cellular processes alone. The dotted line indicates the evolution of the average mutation frequency of 1,100 mice, which grows linearly with time. (C, D) The percentiles and probability distribution functions of the mutation frequency in the RMC assay of in silico wild-type mouse population. The apparent variability arises from the combined effect of intrinsic stochasticity and the (hypergeometric) sampling variability in the RMC protocol (details in the main text).