A DNA-matching technique often used in forensics has been called to the stand.
Fine-grained analysis of DNA found in cell structures called mitochondria suggests that it can vary widely between tissues, making samples tricky to compare.
“I wouldn’t say that it throws other results out the window, but it does throw a curve ball,” said Nickolas Papadopoulos, a Johns Hopkins University geneticist and co-author of the study, published March 4 in Nature.
Mitochondria are found by the hundreds in every human cell. They convert glucose to energy, and possess their own tiny genomes, separate and distinct from the organismal genome found in each cell nucleus.
In the mid-1990s, law enforcement added mitochondrial DNA comparison to its forensic genetic toolkit. Because there are so many mitochondria in each cell, readable copies of their genomes can often be found even when the nuclear genome has been damaged. This is especially useful for old, highly degraded biological samples.
Mitochondrial DNA-matching is based on the assumption that it doesn’t vary much in an individual: Aside from a few inevitable mutations, mitochondrial DNA are generally supposed to be the same in, say, heart cells and hair cells. But when Papadopoulos’ team applied the latest in gene-sequencing technology to mitochondrial genomes from nine tissue types in two people, that’s not what they found.
Instead, each person seemed to have a mixture of mitochondrial genotypes. One DNA variant, for example, was found in about 7 percent of a person’s skeletal-muscle mitochondria, but 90 percent of their kidney mitochondria. That spread was typical.
“It’s more than was thought, and was present in almost every tissue we looked at,” said Papadopoulos. Further research into these variations is needed, but forensic specialists should be careful to compare the same types of tissue, he said.
Upon learning of the paper, John Planz, associate director of the DNA Identity Laboratory at the University of North Texas Health Science Center, cautioned that further studies are needed. High levels of genetic variation between mitochondria that were found in previous studies turned out to be the result of errors in measurement and analysis, he said.
After reading it in depth, he called it “an outstanding piece of work,” and said that its methodology pointed to a new gold standard in analyzing genetic data. “This study gets a double thumbs up from me,” he said.
Mitochondrial DNA analysis is also used in other types of research. Evolutionary family trees are deduced from comparisons of mutations between fossil samples. The same techniques are used to trace the historical flows of human populations.
Those studies involve group patterns and relatively large-scale changes over long periods of time. So they may not be as challenged by the Nature findings as forensic applications are, which try to find perfect matches, said Papadopoulos.
“This requires more study, but it could put a damper on how things have been interpreted to this point,” he said.
Update 3/5/2010: The story originally contained John Planz’ general caveats about the findings; it has since been updated with his strongly favorable view of the study’s details.
Image: Mitochondria in the brain tissue of a rat./Indiana University-Purdue University Indianapolis
Citation: “Heteroplasmic mitochondrial DNA mutations in normal and tumour cells.” By Yiping He, Jian Wu, Devin C. Dressman, Christine Iacobuzio-Donahue, Sanford D. Markowitz, Victor E. Velculescu, Luis A. Diaz Jr, Kenneth W. Kinzler, Bert Vogelstein and Nickolas Papadopoulos. Nature, Vol. 463, No. 7285, March 4, 2010.
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