Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory chain NADH dehydrogenase. Nature (London

Molecular studies on the human mitochondrial ge-home started well before the introduction of the mod-ern nucleic acid cloning, mapping, and sequencing technologies. The compartmentalized character of this genome, its small size, and the ease of its isolation have made it, since its discovery, an attractive object for studies of gene organization and expression in a simple eukaryotic system. As a result, about 10 years ago, mtDNA was the best characterized portion of the hu-man genome. Its physical structure was well under-stood, the unique features of its transcription were known, the two rRNAs and most of the tRNAs en-coded in mtDNA had been identified and mapped, and the first hints of the extraordinarily compact organi-zation of this genome had been discovered (Attardi et al. 1976); furthermore, vidence was lready available about he number of mRNAs and proteins encoded in this genome, and the probable function of some of these proteins (Costantino and Attardi 1975). It was therefore no surprise that when the dideoxy DNA se-quencing technology became available in E Sanger's laboratory in Cambridge, England, the human mito-chondrial DNA was chosen as the most favorable u-karyotic nonviral system on which to test the new tech-nology and at the same time to collect biologically important data (Anderson et al. 1981). One of the most intriguing findings from the se-quence analysis of human mtDNA was the discovery that more than half of its protein-coding capacity re-sides in eight reading frames (Anderson et al. 1981) (Fig. 1), which, with one exception, have no obvious amino acid sequence homology to any of the identified or unidentified reading frames (URF) of Saccharomy-ces cerevisiae (Grivell 1983) and Schizosaccharomyces pombe (Lang et al. 1983), although several of them were later found to occur in mtDNA of other lowe