Open Close
Samstag, C.L., Hoekstra, J.G., Huang, C.H., Chaisson, M.J., Youle, R.J., Kennedy, S.R., Pallanck, L.J. (2018). Deleterious mitochondrial DNA point mutations are overrepresented in Drosophila expressing a proofreading-defective DNA polymerase γ.  PLoS Genet. 14(11): e1007805.
FlyBase ID
Publication Type
Research paper

Mitochondrial DNA (mtDNA) mutations cause severe maternally inherited syndromes and the accumulation of somatic mtDNA mutations is implicated in aging and common diseases. However, the mechanisms that influence the frequency and pathogenicity of mtDNA mutations are poorly understood. To address this matter, we created a Drosophila mtDNA mutator strain expressing a proofreading-deficient form of the mitochondrial DNA polymerase. Mutator flies have a dramatically increased somatic mtDNA mutation frequency that correlates with the dosage of the proofreading-deficient polymerase. Mutator flies also exhibit mitochondrial dysfunction, shortened lifespan, a progressive locomotor deficit, and loss of dopaminergic neurons. Surprisingly, the frequency of nonsynonymous, pathogenic, and conserved-site mutations in mutator flies exceeded predictions of a neutral mutational model, indicating the existence of a positive selection mechanism that favors deleterious mtDNA variants. We propose from these findings that deleterious mtDNA mutations are overrepresented because they selectively evade quality control surveillance or because they are amplified through compensatory mitochondrial biogenesis.

PubMed ID
PubMed Central ID
PMC6289449 (PMC) (EuropePMC)
Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    PLoS Genet.
    PLoS Genetics
    Publication Year
    1553-7404 1553-7390
    Data From Reference
    Aberrations (2)
    Alleles (1)
    Genes (2)
    Human Disease Models (1)
    Natural transposons (1)
    Transgenic Constructs (1)