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Mitochondrial genes cause nuclear mischief

While the nucleus of a cell may be its command headquarters, mitochondria are equally vital--they are the power plants of the cell, and without them all cellular activity would quickly and irrevocably come to a halt. Testifying to their origins as once free-living bacteria, mitochondria have their own DNA, comprising 37 genes in humans on a single circular chromosome. However, most of the mitochondria's presumed ancestral genes have been taken into the cell's nucleus, where they are under the strict control of their host.

The transplanted mitochondrial genes have been faithfully doing their job under new management since they were first appropriated, probably hundreds of millions of years ago. But in this issue, Miria Ricchetti and colleagues show that the over 200 mitochondrial genetic fragments also integrated into the nuclear genome may not be quite so benign. They have continued to invade the human genome, even into the present day, and a large proportion of them take up residence within nuclear genes, possibly disrupting them and causing human diseases.

Scanning the entire human genome, Ricchetti and colleagues found a total of 211 nuclear sequences of mitochondrial origin (NUMTs). Of these, they selected 42, which appeared to be the most recent integrations, for detailed study. Among several important observations, they found that these NUMTs were much less likely to be found in non-coding "junk" DNA and much more likely to insert themselves within highly active genes. Such insertions can cause disease, as shown by the recent discovery of a hemophilia patient with a NUMT interrupting his clotting factor gene.

Much remains to be learned about the functional and temporal dynamics of NUMT insertions, but their potential for harm suggests that many NUMTS, unlike much of the rest of the flotsam that litters our genome, may be selected against quickly. Combined with their differential distribution among human ethnic groups, this may make th
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Contact: Paul Ocampo
pocampo@plos.org
1-415-624-1224
Public Library of Science
6-Sep-2004


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