Strong Purifying Selection In Transmission Of Mammalian Mitochondrial DNA

Main Category: Biology / Biochemistry
Also Included In: Genetics
Article Date: 28 Jan 2008 - 17:00 PDT

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Mammalian mtDNA is maternally transmitted and does not undergo bi- parental recombination in the germ line. This asexual mode of transmission, together with a high rate of mutation, should eventually lead to the accumulation of numerous deleterious mtDNA mutations and a "mutational meltdown" (a phenomenon known as Muller's Ratchet).

Published this week in the open-access journal PLoS Biology, James Stewart, Nils-Goran Larsson, and colleagues show how they utilized a genetic mouse model, the mtDNA mutator mouse, to introduce random mtDNA mutations and followed transmission of these mutations. Maternal transmission of mtDNA is typically subjected to a bottleneck phenomenon whereby only a fraction of the mtDNA copies in the germ cell precursor are amplified to generate the ~105 mtDNA copies present in the mature oocyte. As a consequence of this phenomenon, the established maternal mouse lines carried high levels of a few mtDNA mutations.

They sequenced the entire mtDNA to characterize the maternally transmitted mutations in the established mouse lines. Surprisingly, mutations causing amino acid changes were strongly underrepresented in comparison with "silent" changes in the protein coding genes. These results show that mtDNA is subject to strong purifying selection in the maternal germ line. Such selection of functional mtDNA genomes likely involves a mechanism for functional testing to prevent transmission of mutated genomes to the offspring.

Strong purifying selection in transmission of mammalian mitochondrial DNA.
Stewart JB, Freyer C, Elson JL, Wredenberg A, Cansu Z, et al. (2008)
PLoS Biol 6(1): e10.doi:10.1371/journal.pbio.0060010
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