Healthy people carry disease-causing mitochondrial DNA mutations

July 8, 2014 by Krishna Ramanujan
Structure of the human mitochondrial genome. Credit: Wikipedia/CC BY-SA 3.0

(Medical Xpress)—For the first time, researchers have discovered that disease-causing mutations in mitochondrial DNA (mtDNA) are common in healthy individuals, according to a Cornell study published July 7 in the Proceedings of the National Academy of Sciences.

Previous studies have found associations between mtDNA and many disorders, including cancers, diabetes, autonomous immune diseases, Parkinson's and other age-related diseases. The presence of disease-causing mtDNA mutations in healthy humans could play a major role in the aging process and age-related diseases, according to the study's authors. Future work will try to determine the extent that these mutations contribute to age-related disease.

Most human carry two copies of nuclear DNA, one copy from each parent, and hundreds of copies of mtDNA, inherited only from the mother.

The pathogenic mtDNA mutations in healthy individuals are usually present at within cells, but by random chance during cellular division, the number of pathogenic mutations within some cells can increase. "As individuals age, we expect the frequency of deleterious mutations to increase in a fraction of cells causing malfunctioning mitochondria and defective cells," said Zhenglong Gu, associate professor of nutritional sciences and the paper's senior author.

"If more than 60 percent of mtDNA carry , then there will likely be a problem for that cell," which could be a mechanism that contributes to the aging process and disease, said Kaixiong Ye, a graduate student in Gu's lab who is the paper's lead author.

These mutations are present because natural selection has not been strong enough to remove them, said the researchers. Natural selection would have removed deleterious mutations if they had caused disease that weakened individuals. However, pathogenic mtDNA mutations are usually present at low frequency and buffered by healthy mtDNA, preventing the action of .

The discovery is "not surprising in hindsight, but this is the first time using such a large dataset to unravel the prevalence of pathogenic mtDNA mutations in healthy individuals," said Ye.

The data in this study are from the 1000 Genomes Project, which has sequenced more than 1,000 human genomes but left mtDNA data unanalyzed. Gu hopes this study can raise interest in understanding the role of mtDNA in diseases.

In the next phases of this work, the researchers will investigate whether a healthy diet and lifestyle can slow down the expansion of pathogenic mtDNA mutations. They will also explore the effects of these mutations at the single cell level, investigate the percentage of cells with high-frequency defective mtDNA and determine what happens to these cells as a person ages: Do the cells die, and if they don't die, then what, Gu said.

Explore further: Rare mitochondrial mutations—maybe not so rare?

More information: "Extensive pathogenicity of mitochondrial heteroplasmy in healthy human individuals," by Kaixiong Ye, Jian Lu, Fei Ma, Alon Keinan, and Zhenglong Gu.

Related Stories

Rare mitochondrial mutations—maybe not so rare?

June 8, 2013
French scientists have discovered that supposedly rare mutations in the mitochondria, the 'power plants' of human cells responsible for creating energy, account for more than 7% of patients with a mitochondrial disease manifesting ...

Extremely rare mitochondrial DNA deletions associated with aging can be accurately detected with Droplet Digital PCR

September 4, 2013
A study published today in Aging Cell identifies a new tool to accurately analyze extremely rare mitochondrial DNA (mtDNA) deletions associated with a range of diseases and disorders as well as aging. This approach, which ...

Mechanism that allows bacteria to infect plants may inspire cure for eye disease

August 4, 2013
By borrowing a tool from bacteria that infect plants, scientists have developed a new approach to eliminate mutated DNA inside mitochondria—the energy factories within cells. Doctors might someday use the approach to treat ...

Inheritance of mitochondrial disease determined when mother is still an embryo

October 8, 2012
(Medical Xpress)—The risk of a child to inherit mitochondrial diseases - i. e. malfunction in what is usually referred to as the power plants of the cell - is largely decided when the future mother herself is still an embryo. ...

PGD can permit the birth of healthy children to women carrying mitochondrial DNA disease

May 30, 2011
Pre-implantation genetic diagnosis (PGD) can give women at risk of passing on a mitochondrial DNA disorder to their offspring a good chance of being able to give birth to an unaffected child, a researcher told the annual ...

Scientists advise caution with regard to artificial insemination method

June 17, 2014
The approval of a new treatment method by which three parents will be able to beget a child is being discussed since a few years in Great Britain and will possibly become a reality in two years. The method is supposed to ...

Recommended for you

Gene variant activity is surprisingly variable between tissues

August 21, 2017
Every gene in almost every cell of the body is present in two variants called alleles—one from the mother, the other one from the father. In most cases, both alleles are active and transcribed by the cells into RNA. However, ...

Genome analysis with near-complete privacy possible, say researchers

August 17, 2017
It is now possible to scour complete human genomes for the presence of disease-associated genes without revealing any genetic information not directly associated with the inquiry, say Stanford University researchers.

Science Says: DNA test results may not change health habits

August 17, 2017
If you learned your DNA made you more susceptible to getting a disease, wouldn't you work to stay healthy?

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

Phenotype varies for presumed pathogenic variants in KCNB1

August 16, 2017
(HealthDay)—De novo KCNB1 missense and loss-of-function variants are associated with neurodevelopmental disorders, with or without seizures, according to a study published online Aug. 14 in JAMA Neurology.


Adjust slider to filter visible comments by rank

Display comments: newest first

1 / 5 (2) Jul 08, 2014
From Kohl (2013) "In flies, ecological and social niche construction can be linked to molecular-level cause and effect at the cellular and organismal levels via nutrient-dependent changes in mitochondrial tRNA and a nuclear-encoded tRNA synthetase. The enzyme enables attachment of an appropriate amino acid..."

Conserved microRNA editing in mammalian evolution, development and disease

Excerpt: "…site-specific miRNA editing is an evolutionarily conserved mechanism, which increases the functional diversity of mammalian miRNA transcriptomes."

Excerpt 2): "…miRNA editing is an integral and evolutionarily stable feature of mammalian transcriptomes."

My comment: It's time for social scientists and serious scientists alike to admit that site-specific miRNA editing is nutrient-dependent and pheromone-controlled. Biological facts continue to refute the pseudoscientific nonsense of mutation-initiated natural selection and evolved biodiversity.
Captain Stumpy
not rated yet Jul 09, 2014
Biological facts continue to refute the pseudoscientific nonsense of mutation-initiated natural selection and evolved biodiversity
DOES your model make any changes to the nucleotide sequence of the genome of an organism, virus, or extrachromosomal genetic element?
This is a yes or no answer
THIS is the DEFINITION of MUTATION- to which you answered
--Thanks for asking
Therefore you are BLATANTLY LYING and attempting to PROMOTE PSEUDOSCIENCE by sowing confusion, doubt and idiocy

These are YOUR WORDS, mensa boy, NOT MINE
and they can be proven, TIME AND AGAIN, with links showing YOU POSTED THEM

continuing to post PSEUDOSCIENCE will only decimate your already challenged and tenuous credibility

I wonder if you can be reported to the licensing agency or board?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.