Morris, J. et al. Cell Rep. 21, 2706–2713 (2017).

Organellar genomes can exhibit genetic variation, even within cells, with consequences for disease penetrance and organellar inheritance. Although attempts have been made to sequence DNA at single-organelle resolution, they have been limited to short genomic regions. Morris et al. now develop an approach to sequence the whole genome of individual mitochondria by isolating single organelles via micropipette, amplifying the full genome using specific primers and nested or seminested PCR, and then carrying out sequencing library construction. Using the technique, the researchers assessed the mitochondrial genomes of mouse neurons and astrocytes, and they found high levels of single-nucleotide variation at multiple loci across individuals, across cells and within cells. Mitochondria of human neurons in primary culture appeared to have slightly lower variation, though further sampling is needed to establish this.