Affiliation:
1. Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94158–2200, USA.
Abstract
High copy number and random segregation confound genetic analysis of the mitochondrial genome. We developed an efficient selection for heritable mitochondrial genome (mtDNA) mutations in
Drosophila
, thereby enhancing a metazoan model for study of mitochondrial genetics and mutations causing human mitochondrial disease. Targeting a restriction enzyme to mitochondria in the germline compromised fertility, but escaper progeny carried homoplasmic mtDNA mutations lacking the cleavage site. Among mutations eliminating a site in the cytochrome c oxidase gene,
mt:CoI
A302T
was healthy,
mt:CoI
R301L
was male sterile but otherwise healthy, and
mt:CoI
R301S
exhibited a wide range of defects, including growth retardation, neurodegeneration, muscular atrophy, male sterility, and reduced life span. Thus, germline expression of mitochondrial restriction enzymes creates a powerful selection and has allowed direct isolation of mitochondrial mutants in a metazoan.
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
98 articles.
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