A novel mitochondrial DNA-like sequence in the human nuclear genome

We describe here a nuclear mitochondrial DNA-like sequence (numtDNA) that i s nearly identical in sequence to a continuous 5842 bp segment of human mit ochondrial DNA (mtDNA) that spans nucleotide positions 3914 to 9755. On the basis of evolutionary divergence among modern primates, this numtDNA molec ule appears to represent mtDNA from a hominid ancestor that has been transl ocated to the nuclear genome during the recent evolution of humans. This nu mtDNA sequence harbors synonymous and nonsynonymous nucleotide substitution s relative to the authentic human mtDNA sequence, including an array of sub stitutions that was previously found in the cytochrome c oxidase subunit 1 and 2 genes. These substitutions were previously reported to occur in human mtDNA, but subsequently contended to be present in a nuclear pseudogene se quence. We now demonstrate their exclusive, association with this 5842-bp n umtDNA, which we have characterized in its entirety. This numtDNA does not appear to be expressed as a mtDNA-encoded mRNA. It is present in nuclear DN A from human blood donors, in human SH-SY5Y and A431 cell lines, and in p(0 ) SH-SY5Y and p(0) A431 cell lines that were depleted of mtDNA. The existen ce of human numtDNA sequences with great similarities to human mtDNA render s the amplification of pure mtDNA from cellular DNA very difficult, thereby creating the potential for confounding studies of mitochondrial diseases a nd population genetics. (C) 1999 Academic Press.