A new study from deCODE genetics uses pedigrees and sequence data from 64,806 Icelanders to shed light on the rate and nature of mutations in mitochondrial DNA (mtDNA) and the peculiar dynamics of its maternal transmission.
In a paper published today in Cell, scientists from deCODE genetics, a subsidiary of Amgen, present the largest study to date of germline mtDNA mutations in humans and their transmission across 116,663 mother-child pairs. The study documents the astonishing extent of hypermutability at some positions in mtDNA, including the well-known deleterious A>G mutation at position 3243 which causes the MELAS syndrome. The mutation occurred 15 times in the 2,548 matrilineal pedigrees, but typically disappeared after several generations, due to its severe impact on the health of carriers.
Strong aggregate evidence was uncovered for selection against many such short-lived deleterious mtDNA mutations in the pedigrees. The deCODE team also reported evidence for an extensive earlier episode of negative selection affecting mitochondria, called germline selection, where poorly functioning mitochondrial DNA molecules are discarded during the development of oocytes. Finally, they used the large number of transmissisons of mtDNA mutations in the pedigrees to reliably estimate that individuals inherit, on average, only around 3 units of mtDNA from their mothers – fewer than indicated by previous studies.
