Genomic structure of murine mitochondrial DNA polymerase-gamma.

We have sequenced a genomic clone of the gene encoding the mouse mitochondrial DNA polymerase. The gene consists of 23 exons, which span approximately 13.2 kb, with exons ranging in size from 53 to 768 bp. All intron-exon boundaries conform to the GT-AG rule. By comparison with the human genomic sequence, we found remarkable conservation of the gene structure; the intron-exon borders are in almost identical locations for the 22 introns. The 5\u27 upstream region contains approximately 300 bp of homology between the mouse and human sequences that presumably contain the promoter element. This region lacks any obvious TATA domain and is relatively GC rich, consistent with the housekeeping function of the mitochondrial DNA polymerase. Finally, within the 5\u27 flanking region, both mouse and human genes have a region of 73 bp with high homology to the tRNA-Arg gene

Mitochondrial DNA Mutations May Contribute to Aging Via Cell Death Caused by Peptides that Induce Cytochrome c Release

Mice wherein the wild-type mitochondrial DNA polymerase (pol γ) is replaced by a proofreading-deficient version are born with mutation frequencies in mitochondrial DNA (mtDNA) much higher than are ever normally seen in old rodents or humans. These mice, however, are phenotypically normal at birth, raising the question regarding how the much lower frequencies observed in normal aging could possibly contribute to the aging process. In contrast, transgenic mice with cardiac-specific expression of a proofreading-deficient poly γ from birth onwards accumulate mtDNA mutations to levels normally seen in aging. But these mice develop dilated cardiomyopathy suggesting that age-related mtDNA mutations are pathogenic. Using computer simulation, we show that both findings are predicted based on the hypotheses that (1) rare lethal mutations that cause apoptosis underlie the pathogenesis of mutagenesis in mtDNA and (2) most sporadic mtDNA mutations are phenotypically recessive and therefore nonpathogenic. Biochemical evidence is presented that mitochondria with mtDNA mutations generate a peptide that causes the release of cytochrome c, providing a mechanism for the increased apoptosis observed in aging. Simulation also predicts that normal, age-related accumulation of mtDNA mutations causes significant levels of cell death. These findings suggest that mtDNA mutations play an important role in the aging process and that their pathogenic mechanism is linked to apoptosis

The Quantum Double Model with Boundary: Condensations and Symmetries

Associated to every finite group, Kitaev has defined the quantum double model for every orientable surface without boundary. In this paper, we define boundaries for this model and characterize condensations; that is, we find all quasi-particle excitations (anyons) which disappear when they move to the boundary. We then consider two phases of the quantum double model corresponding to two groups with a domain wall between them, and study the tunneling of anyons from one phase to the other. Using this framework we discuss the necessary and sufficient conditions when two different groups give the same anyon types. As an application we show that in the quantum double model for S_3 (the permutation group over three letters) there is a chargeon and a fluxion which are not distinguishable. This group is indeed a special case of groups of the form of the semidirect product of the additive and multiplicative groups of a finite field, for all of which we prove a similar symmetry