Different levels at which purifying selection can occur in the maternal germline. (top) Genomes with mutations could be blocked from replication or selectively destroyed without the need for gene expression. (middle) A fragmented mitochondrial network would allow functional testing of individual mtDNA molecules. The presence of a mutated mtDNA molecule would result in a mitochondrion with deficient respiratory chain function, which, in turn, would lead to selection against and/or destruction of this mitochondrion. (bottom) Cells with high levels of mutated mtDNA may fail to compete with respiratory chain–competent cells and may be selected against or undergo apoptosis. The colors indicate mutant (red) and wild-type (blue) mtDNA (top); respiratory chain–deficient (red) and normal (blue) mitochondria (middle); and respiratory chain–deficient (red) and normal (blue) cells (bottom).