The Roles of Mutation Rate and Selective Pressure on Observed Levels of the Human Mitochondrial DNA Deletion$\text{mtDNA}^{4977}

The mitochondrial deletion$\text{mtDNA}^{4977}$has been found at high levels in individuals with certain neuromuscular and neurological diseases, and at lower levels in older normal individuals. We use experimental estimates of the mutation rate of$\text{mtDNA}^{4977}$and of the half-life of mitocho...

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Bibliographic Details
Published in:Lecture notes-monograph series 2003-01, Vol.40, p.247-258
Main Authors: Navidi, William C., Tavaré, Simon, Arnheim, Norman
Format: Article
Language:English
Subjects:
Biological Findings and Sequence Data
Embryonic cells
Genetic mutation
Genomes
Human genetics
Mitochondria
Mitochondrial DNA
Molecules
Mortality
Nervous system diseases
Substantia nigra
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Summary:The mitochondrial deletion$\text{mtDNA}^{4977}$has been found at high levels in individuals with certain neuromuscular and neurological diseases, and at lower levels in older normal individuals. We use experimental estimates of the mutation rate of$\text{mtDNA}^{4977}$and of the half-life of mitochondrial genomes to construct a model of mitochondrial replication and mutation that is consistent with observed levels of the deletion. We conclude that deleted genomes have a slight selective advantage, at least in some tissues. Our results suggest that for an individual to attain a clinically significant level of the deletion, between 0.2% to 0.5% of the mitochondrial genomes in the original oöcyte must have been deleted.
ISSN:0749-2170