Stochastic modelling, Bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism

• DOI: 10.7554/elife.07464
• Publication Date: 2015-06-02T11:32:40Z
• Authors: Iain G Johnston; Joerg P Burgstaller; Vitezslav Havlicek; Thomas Kolbe; Thomas Rülicke; Gottfried Brem; Jo Poulton; Nick S Jones
• Keywords: Heteroplasmy; Approximate Bayesian Computation

Dangerous damage to mitochondrial DNA (mtDNA) can be ameliorated during mammalian development through a highly debated mechanism called the mtDNA bottleneck. Uncertainty surrounding this process limits our ability address inherited diseases. We produce new, physically motivated, generalisable theoretical model for populations development, allowing first statistical comparison of proposed bottleneck mechanisms. Using approximate Bayesian computation and mouse data, we find most support combination binomial partitioning mtDNAs at cell divisions random turnover, meaning that exact magnitude copy number depletion is flexible. New experimental measurements from wild-derived pairing in mice confirm predictions model. analytically solve mathematical description mechanism, computing probabilities disease onset, efficacy clinical sampling strategies, effects potential dynamic interventions, thus developing quantitative experimentally-supported stochastic theory