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NIH Research Matters

March 15, 2010

Unexpected Diversity in Mitochondrial DNA

A new approach for analyzing DNA shows that each person's mitochondrial DNA (mtDNA) is surprisingly variable in different body tissues. The finding may eventually prove useful for spotting and monitoring cancer, as it leads to telltale mtDNA variations that can be detected in the bloodstream.

Scanning electron micrograph of pill-shaped organelle filled with folded membranes.

A mitochondrion fractured to reveal its internal structure. Image by Dr. David Furness, all rights reserved by Wellcome Images.

Mitochondria are tiny capsule-shaped structures that produce energy for the cell. Each cell has dozens to hundreds of mitochondria, and each mitochondrion contains several copies of circular strands of DNA. This DNA is distinct from the main genome in the cell's nucleus, which is inherited from both the mother and father. Mitochondria, in contrast, are passed directly from a mother's egg cell to her offspring. Until recently, most scientists believed that nearly all of a person's cells contain identical copies of mtDNA inherited from the mother.

A research team led by Drs. Nickolas Papadopoulos and Bert Vogelstein of Johns Hopkins University used new, highly sensitive DNA sequencing technologies to take a closer look at mtDNA variability in different tissues within several individuals. The technique can detect relatively rare single-letter variants in stretches of DNA—even those found in as few as 1 in 10,000 mitochondrial genomes. The research was supported by NIH’s National Cancer Institute (NCI) and the Howard Hughes Medical Institute.

In the March 4, 2010, advance online edition of Nature, the researchers described a series of mtDNA analyses, including a detailed evaluation of 10 different tissues taken from a single person. Although most analyzed mtDNA was identical, the researchers detected at least 1 variant form of mtDNA in each tissue, and 4 tissues harbored at least 4 variants. The proportion of variant mtDNA in tissues differed widely. In some cases, certain tissues—like kidney and liver—shared a variant that wasn't found in other tissues.

To get a better sense of how these variants might arise, the scientists studied sets of parents and their offspring. As expected, mtDNA variants were not inherited from fathers. A small number of variant mtDNAs did seem to pass directly from mother to offspring. But inheritance is unlikely to account for the wide variability seen in different tissues. The researchers believe that most variations in mtDNA must arise during embryonic and fetal development. That would explain why some variants were found only in certain tissues.

Analysis of both healthy and cancerous tissues also identified several cancer-specific mtDNA mutations. The mutations were detectable in the blood plasma of 2 colorectal cancer patients, and the levels dropped after the tumors were surgically removed. Cancer-specific mutations in nuclear DNA were also found in the bloodstream, but the concentration of mutant mtDNA was significantly greater and so could be identified in much smaller blood samples. With further study, mtDNA may hold promise for detection and post-treatment monitoring of cancer. It's also less costly than nuclear DNA analysis.

"We were surprised to find how much the DNA of mitochondria varies within each individual," says Papadopoulos. "The bottom line is there is no single mitochondrial genome in humans."

—by Vicki Contie

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Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.

NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.

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This page last reviewed on December 3, 2012

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