The mitochondrial bottleneck. (A) Mitochondrial DNA (mtDNA) copy number throughout Drosophila oogenesis. Cartoon of the ovariole at the top which contains developing follicles including the oocyte (blue) with a newly developing fertilized egg on the right. Germline stem cells (GSCs) are at the anterior of a specialized structure called the germarium. GSCs are present throughout the adult lifespan and continuously give rise to the germline. Primordial germ cells (PGCs) are the first cells formed at the posterior of the newly fertilized and deposited egg. The graph represents mtDNA copy number relative to the egg measured using quantitative mtDNA fluorescence in situ hybridization (FISH) and verified with qPCR for accessible stages (eggs, PGCs) (Hurd et al. 2016). mtDNA copy number greatly increases during follicle development then decreases when PGCs form. The green lines represent developmental time points that have been implicated in the genetic bottleneck due to decreased mtDNA copy number, mitochondrial dynamics, and mtDNA replication. (B) mtDNA copy number and genotypic variance throughout mammalian follicle development. Germ cell stages are indicated at the top. The profound drop in mtDNA copy number in PGCs followed by ~500-fold increase in copy number to mature oocyte enables clonal proliferation of mtDNA as well as passive selection of the best oocyte at the cellular level, the so-called 'ovarian bottleneck' (Wolf et al. 2017). Following fertilization, the oocyte divides and forms the inner cell mass of the blastocyst with little mtDNA replication (McConnell & Petrie 2004), where ~3 cells will develop into the embryo. In this 'postfertilization bottleneck' there may be active selection at the mtDNA level as well as passive compartmentalization. Evidence to date suggests that the major component of the variance in germline development arises prenatally during oogenesis (Li et al. 2016) and postnatally during folliculogenesis (Johnston et al. 2015).