“…There has been considerable debate about whether the mechanism of this bottleneck involves an actual decrease in the number of mitochondrial genome copies versus co-segregation of genetically homogeneous groups of mitochondrial DNA (e.g., Jenuth et al, 1996;Cao et al, 2007;Cree et al, 2008;Wai et al, 2008;Carling et al, 2011). Nevertheless, in order to better predict the change in heteroplasmy frequencies between generations, previous studies have sought to infer the size of the oogenic bottleneck, either through direct observation (in mice) of the number of mitochondrial DNA genome copies (Cree et al, 2008;Cao et al, 2007), or through indirect measurement, making statistical conclusions about the bottleneck size based on observed frequency changes between generations (Johnston et al, 2015;Rebolledo-Jaramillo et al, 2014;Millar et al, 2008;Hendy et al, 2009;Li et al, 2016). Recently, Johnston et al (2015) have proposed a statistical framework that combines direct observations of mtDNA copy number with genetic variance in order to make inferences about the dynamics of the oogenic bottleneck.…”