Heteroplasmy is the presence of more than one type of a genome (in this context, mitochondrial DNA) within a cell or organism. Put another way, a heteroplasmy is when more than one result exists for the same position in a person's sequence.
- If each result exists frequently enough in a person's mtDNA, then the sequencing process will detect both results.
- Identifying a heteroplasmy can be subjective.
- In general, to identify a heteroplasmy, at least one third of the copies of mtDNA need to have each result.
- A heteroplasmy may be written in several ways. The most common forms are, for example, 16093C/T or 16093Y, where the Y represents the C/T combination of alleles.
| Symbol | Meaning | | Symbol | Meaning |
|---|
| A |
A (Adenine) |
|
T |
T (Thymine) |
| C |
C (Cytosine) |
|
G |
G (Guanine) |
| U |
U (Uracil) |
|
S |
C or G |
| M |
A or C |
|
Y |
C or T |
| R |
A or G |
|
K |
G or T |
| W |
A or T |
|
V |
A or C or G |
| H |
A or C or T |
|
B |
C or G or T |
| D |
A or G or T |
|
X |
G or A or T or C |
| N |
G or A or T or C |
|
|
The following information is what we understand so far about how mtDNA is passed on from mother to child, and how this relates to heteroplasmy. As more research reveals additional facts and our understanding of these processes increases further, we will update this information accordingly.
Each human cell contains hundreds or thousands of mitochondria, and each mitochondrion contains several copies of its own DNA. When a mutation occurs, it does not mutate every copy of a person's mtDNA; it occurs in only one copy. The mutation may become more frequent as that DNA is duplicated and passed on to the next generation. For the purposes of the discussion below, we will refer to the original mtDNA sequence as the ancestral genome, and to the mutated mtDNA sequence as the descendant genome.
At one point during oogenesis (the process by which the egg cell is produced), the number of mitochondria present in the cell is dramatically reduced from hundreds to perhaps as few as ten. These ten then multiply back into the hundreds in the offspring's cells. If one or several of these ten happen to have a mutation, then the child will have a similar proportion of the descendant genome among the mitochondria in his or her cells. It generally takes several generations for a mutation to spread in this manner to most or all copies of a person's mtDNA. This is same process by which new haplogroup branches evolve.
If the mother has a heteroplasmy, each of her children can experience any of these outcomes:
- The child has a heteroplasmy at the same position. The child inherited some mitochondria with the ancestral genome and some with the descendant genome, so the child has some of each in his or her cells. The proportion of ancestral to descendant genome can vary in each generation and in each child.
- The child has only the descendant genome. Only mitochondria with the mutation were passed on to the child. If the child is female, then her children will also inherit only descendant genome.
- The child has only the ancestral genome. Only mitochondria without the mutation were passed on to the child. If the child is female, then her children will also inherit only the ancestral genome.
Because in each generation it is possible for the child to inherit the heteroplasmy, heteroplasmies may last for several or many generations. In each generation along the way, some children may inherit only the ancestral or only the descendant genome. Additionally, an mtDNA sequence test will not detect a heteroplasmy if one value is found in a great majority of the mitochondria and the other value is found in only a small minority. Therefore a heteroplasmy may be present which would not be detected. This makes it difficult to estimate the true frequency of heteroplasmy. Logically, if all mtDNA mutations progress through a state of heteroplasmy, then the frequency of heteroplasmy is equal to or greater than the mutation rates proposed for mtDNA (where these mutation rates are calculated using only those individuals with only the descendant genome).
We cannot identify from a single person's sequence which result in a heteroplasmy is the ancestral and which is the descendant. If you have a heteroplasmy and would be interested in determining which is the ancestral and which is the descendant result, you should test your most distant known relative along your maternal line, such as a second or third cousin. Because heteroplasmies can last several generations, the more distantly related you are to the relative you test, the more likely the mutation took place only on your branch of the family, and therefore the more likely that this relative's result represents the ancestral.
While we do not examine or discuss medical implications of any person's mtDNA full sequence, one of the questions we are asked most frequently is the medical or physiological implications of having a heteroplasmy. There is no more medical or physiological impact of having a heteroplasmy than there is of having only the mutation at the same position in the mtDNA. In other words, if you find that a mutation at this position is not known to be associated with any physiological issue, then the heteroplasmy is not, either. If you find that a mutation at this position is or may be associated with a physiological issue, then the heteroplasmy may potentially produce the same issue, or may produce a lesser form of it because not all of the mtDNA has the mutation.