Large reservoir of mitochondrial DNA mutations identified in humans

August 11, 2008

Researchers at the University of Newcastle, England, and the Virginia Bioinformatics Institute at Virginia Tech in the United States have revealed a large reservoir of mitochondrial DNA mutations present in the general population. Clinical analysis of blood samples from almost 3,000 infants born in north Cumbria, England, showed that at least 1 in 200 individuals in the general public harbor mitochondrial DNA mutations that may lead to disease.

The findings, which highlight the need to develop new approaches to prevent the transmission of mitochondrial diseases, were published in The American Journal of Human Genetics.

Mitochondria, the "engines" present in each cell that produce adenosine triphosphate, are passed from mother to offspring. Mutations in mitochondrial DNA inherited from the mother may cause mitochondrial diseases that include muscle weakness, diabetes, stroke, heart failure, or epilepsy. In almost all mitochondrial diseases caused by mutant mitochondrial DNA, the patient's cells will contain a mixture of mutant and normal mitochondrial DNA. The proportion of mutant mitochondrial DNA in most cases determines the severity of disease.

Previous estimates from epidemiological studies suggested that mitochondrial diseases affect as many as one person in 5,000. However, the incidence of new mitochondrial mutations and the prevalence of those carrying these mutations were never fully established due to limitations in the methods used. Most of the earlier estimates of the frequency of mitochondrial DNA mutations in the general population, for example, have depended on identification of clinically affected patients and subsequent retracing of inheritance on the maternal side of the family. This approach fails to detect the gradual accumulation of mutations in some members of the population, including those individuals who harbor mitochondrial DNA mutations but who otherwise do not show the symptoms of disease.

Dr. David Samuels, Assistant Professor at the Virginia Bioinformatics Institute and an author on this study, commented: "We know from many clinical studies of patients and their families that our cells can tolerate a rather large amount of mutant mitochondrial DNA with no significant loss of function. From that observation we have suspected that there may be a large number of people in the general population who carry pathogenic mitochondrial DNA mutations, but who are not obviously ill with a mitochondrial disease. This study gives us, for the first time, a measurement of the number of these carriers of pathogenic mitochondrial DNA mutations in the general population. One in every 200 individuals is a lot of people – around 1.5 million people in the United States alone. "

The scientists looked at 10 mitochondrial DNA mutations (arising from single nucleotide replacements) often found in patients with mitochondrial disease. By taking advantage of a high-throughput genotyping system that uses mass spectrometry measurements, the researchers were able to detect mutated mitochondrial DNA at high sensitivity. In each positive case, DNA cloning and sequencing were used to confirm the findings. By looking at differences in tissue samples from mother and child, the researchers were also able to estimate the rate at which new DNA mutations had arisen in the population. The incidence of new mutations was close to 100 for every 100, 000 live births.

Dr. Samuels commented: "These new clinical measurements have given direct evidence for the widespread incidence of pathogenic mitochondrial DNA mutations in the human population. These findings emphasize the pressing need to develop effective ways to interrupt the transmission of these mutations to the next generation."

Citation: Hannah R. Elliott, David C. Samuels, James A. Eden, Caroline L. Relton, Patrick F. Chinnery (2008) Pathogenic mitochondrial DNA mutations are common in the general population. American Journal of Human Genetics 83(2): 254-260. doi:10.1016/j.ajhg.2008.07.004

Source: Virginia Tech

Explore further: Nuclear transfer of mitochondrial DNA in colon and rectal cancer

Related Stories

Technique for 'three-parent baby' revealed

April 3, 2017

Details of a pioneering IVF technique using mitochondrial replacement therapy (MRT) have been revealed, giving hope to those families with inheritable mitochondrial disorders that they may be able to have healthy children ...

How the nervous system controls tumor growth

March 22, 2017

(Medical Xpress)—From the time it first comes online during development the nervous system begins to exact precise control over many biologic functions. In some cases, too much control. When it does, a little nerve-squelching ...

Peroxisomes—the hybrid organelle

February 10, 2017

Like the human body itself, cells have structures within them that perform special tasks. These cellular structures are called organelles, and discovering more about organelles is key to unlocking the reasons why certain ...

Mitochondrial DNA mutations: The good, the bad, and the ugly

January 13, 2015

(Medical Xpress)—Programmers typically evolve new code by copying and modifying existing code to meet new needs. With the more advanced programming languages, they also make use of something known in the business as polymorphism—the ...

Recommended for you

New insights on triggering muscle formation

April 26, 2017

Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a previously unrecognized step in stem cell-mediated muscle regeneration. The study, published in Genes and Development, provides new ...

Risk of obesity influenced by changes in our genes

April 25, 2017

These changes, known as epigenetic modifications, control the activity of our genes without changing the actual DNA sequence. One of the main epigenetic modifications is DNA methylation, which plays a key role in embryonic ...


Adjust slider to filter visible comments by rank

Display comments: newest first

1 / 5 (4) Aug 11, 2008
Wait a second... I thought mutations led to _better_ organisms (evolution). Are you telling me that evolution isn't fact?

In fact, now that I think about it, where are all the "in-betweens"? You know, those evolved animals that aren't quite there yet? Shouldn't the world be flooded with a wide degree of these since evolution takes millions to billions of years? Logic dictates that there should practically be a continuum of evolution states from one species to the next.

Also, while we're at it, could someone explain how evolutions accounts for mutations crossing the species line in which you know have different numbers of chromosomes? Every chromosonal defect I've ever heard of (too many or missing chromosomes) results in a non-viable animal. Or in the best case, a weakened animal that is often unable to reproduce.

Also, could someone please provide the mathematical probability of the following circumstances:
(a) mutation results in a positive mutation
(b) mutation results in an animal that can reproduce
(c) enough mutated animals occur to create a self-sustaining population (this requires (1) that animals are geographically close and (2) animals are chronologically close so that they are within breeding age)

4 / 5 (4) Aug 11, 2008
Are you one of those retard american religious type people or just plain dumb?
1 / 5 (3) Aug 11, 2008
Are you one of those retard American religious type people or just plain dumb?

I am one such survivor, perhaps genetically disposed to religious origins. Religious support groups & larger families (perhaps lack of birth control or pooling of resources) may be a selective advantage for persistence.

Why consider infidel or heathen authority as superior, until they can reproduce better than my group, or show compassion perceived as superior to my own.

IMO Religious paradigms are still mortal, intrigued by science, but must always transcend this world. The world is molded by a foundation, shifted only by proving those reproductive values are less successful than others.

With larger family sizes for religious groups, its hard to prove mother nature always prevails against God?
not rated yet Aug 11, 2008
Mutations are changes and as such they are per se not harmful or advantageous by themselves. When combined with the environment one is living, these mutations may have positive or negative effect for the suitability of the individual. If we think that mitochondria's work is to create energy for the cells and as such it's already top-notch design, then probably most mutations happening to them are harmful. When there are no functioning MC's left in cell, that cell will die, but even at reduced level it's functioning will be less than optimal. How much degradation is allowed, I don't know, but the article gives the impression that there's room for quite a lot of mishaps before cells workings are severely hindered. How to prevent these MC mutations from being inherited is something that might raise difficult issues. How to select only those best eggs for that developing next generation? Maybe there will be some new technique to get the cells to expel those mutated MC DNA.
not rated yet Sep 10, 2008
I agree with killerkeeley's sentiment in respect of the comments by Icester.

Most of those issues have been explained over and over and would take quite a lot of space to repeat. Some others would take considerable time and effort to explain and would probably not be read anyway.

However, to clarify something that may not have been noticed:

There is evidence that every single person has many mutations but most of these are harmless - some are inheritable and some are not.

What is inherited is some of those mutations to sperms and eggs that make viable offspring.

You could be infected by a virus or a proto-virus that will splice itself into your genes and thus make a significant difference in the genes of your off-spring.

The differences in our genes may or may not make any noticeable differences to the way we look or function but then again maybe they will this is all random.

Most mutations that people notice are ones that are extremely detrimental but the vast majority of mutations that have little or no discernable effect go unnoticed.

Is some peoples predeliction to narcotic dependence a mutation or is it the reverse.

One obvious mutation and evolutionary change in peoples gene pool is tolerance to milk.

Yes for all you foolish people that refuse to understand or even listen:-

It has been worked out that just about everybody was lactose intolerant at one time and now those poor souls are the exception in Western societies at least.

Why? because they either had lactose tolerance or they had less chance of survival over a number of generations.

Now things are swinging around and due to modern medicines there are a great many variations in our gene pools that can survive where once they would not or they can survive more easily now where once it was more difficult.

Just look at modern western society pressures and you can see evolution still hard at work.


Folks are having children a lot later now in fact many are having their first child at an age where once they would have been grand parents.

What evolutionary pressures is this putting on people?

It is easy to see that those people that would become infertile later in life will find that they are having less children in this society perhaps even none at all. And those that are more fertile can have more. Plus with optional birth we have situation where people that are selfish may have no children while those that are irresponsible may have many children.

People that cannot cope with high stress or big cities may die out or go crazy and become mate-less.

And so it goes on evolution is still hard at work in our changing society.

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.