The Other Genome

Abstract

Since the discovery that Leber hereditary optic neuropathy (LHON) results from mutations in mitochondrial DNA (mtDNA), considerable attention has been focused on this alternative genome and on development of the scientific tools needed to study this remarkable genetic pathway (1)(2). In this issue, Chen et al. (3) describe the application of temporal temperature gradient gel electrophoresis to the detection of mtDNA mutations and show that this technique offers great promise in this application. The study of mitochondrial gene mutations presents investigators with new technical problems not inherent to the study of nuclear gene mutations. This genome is thought to be derived from an evolutionarily ancient organism that parasitized primitive cells, conferring on them enhanced oxidative capacity and the capability of making profitable use of atmospheric oxygen, a fairly toxic substance. The structure of the present day human mitochondrial genome reflects its unusual origin. The mitochondrial genome is a small (16.5 kb) circular DNA encoding only 13 proteins, 2 rRNAs, and a set of tRNAs. All proteins encoded by the mitochondrial genome are components of the mitochondrial electron transport chain, the energy-transducing, oxidative apparatus of the cell. Unlike nuclear genes, which exist in pairs by virtue of their location on paired chromosomes, mitochondrial genes exist in numerous copies per cell, with each mitochondrion containing several copies of the genome and each cell containing many mitochondria. In the case of a nuclear gene, only a limited number of combinations of mutated genes are possible: a situation in …