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Understanding mtDNA Heteroplasmy

What is Mitochondrial DNA?

Mitochondria were once tiny organisms with their own unique DNA. These organisms originally developed on their own outside of cells, but early on in evolution, they formed a symbiotic relationship with cells bringing their unique DNA with them. This unique DNA is known as Mitochondrial DNA (mtDNA). 

mtDNA, just like other DNA, is made up of pairs of the nucleotide bases guanine (G), adenine (A), thymine (T), and cytosine (C). At each position, there is a base pair of G, A, T, or C. Each position is assigned a number. Because of the atomic structure of these four chemicals, G is always paired with C, and A is  always paired with T, and vice versa.


Just as with other types of DNA, over time, copy errors occur. These small copy errors are called mutations. Sometimes when DNA is replicated, one base pair may be substituted for another. For example, in a particular base pair, adenine (A) might be inadvertently substituted for guanine (G). To track these changes, we use a universal reference sequence. Typically, this is the Revised Sapiens Reference Sequence (RSRS), which represents the ancestral sequence for all human mtDNA sequences. It serves as a standard to which all mutations are compared. In the RSRS reference sequence, each base pair is assigned a location number and a reference value for that location, such as A or G. If a person’s sequence differs from the reference sequence, it is assumed that a mutation has occurred after the original sequence. We call the original value the ancestral value and any other value the derived value.

When a mutation is discovered in a base pair, it is reported as the ancestral value, followed by the location, and then the mutated (derived) value. For example, if location 769 has an ancestral value of A in the RSRS standard and you have a derived value of guanine (G), then this mutation will be reported as A769G.


There are many mitochondria in each cell, so sometimes different mitochondria in the same cell can have different mutations. For example, at a particular position, adenine (A) may be substituted for guanine (G) in some (but not all) of the mitochondria within a cell. This is essentially a mutation in progress. Eventually, all of the mitochondria in that person’s descendants could have G. However, during this transition period, it is called a heteroplasmy because both A and G are seen at this location in the same individual.

If more than 20% of the mitochondria tested show this difference, we report it as a heteroplasmy. A heteroplasmy is written with the same pattern as other derived mtDNA values. However, since more than one value is found at the location, we cannot report it with the standard letters of A, C, T, or G. There can be different combinations of base pairs in a heteroplasmy, so different letters are used to represent them. Here is a chart of the different combinations you may find:

Symbol  Meaning 
U U (Uracil) 
A or C 
R A or G 
W A or T 
H A or C or T 
D A or G or T 
N G or A or T or C 
S C or G 
Y C or T 
K G or T 
V A or C or G
B C or G or T
X G or A or T or C

Going back to our example of A769G, if location 769 has A in some mitochondria and G in others, then it will be reported as A769R.

That means when you look at your mtDNA mutation list, if you see one that has a letter other than G, A, T, or C, you know you have a heteroplasmy. Some people have more than one, so be sure to look at all of your mutations.

How Heteroplasmy Affects Matching

In normal matching, a difference is counted when another person does not share the same mutation as you. For example, if you and another person both have A769G, this is a matching mutation. If another person still has the reference value of A, while you have the derived value of G (reported as A769G), then this is counted as a Genetic Distance of 1, meaning that it is one difference.

With heteroplasmic mutations, you match other people who share the same heteroplasmy or original reference value. For example: 

In the mutation A769G, the reference value is A. If you have A769R, then you have both A and G at location 769. Remember that heteroplasmy is a mutation in progress. Because the mutation is not complete, you will match people who also have a mutation in progress and people who have no mutation at all. In other words, you will match people with 769A and 769R. You will not match people with 769G. This means that anyone with A769G will be counted as a Genetic Distance of 1 with you.

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