I am working on a system that annotates variants in human DNA sequences. One of the pieces of information reported is the zygosity of the variant. I noticed that mitochondrial variants are also shown to be either homo- or heterozygous.

How does that make sense? Does it make sense? As far as I know, the mitochondrial DNA is just a single, circular DNA molecule. So I can understand considering all mitochondrial variants heterozygous, by definition. I could also accept that one could think of them as homozygous by definition. I just don't see how some variants can be homo- and others heterozygous. Am I missing something or is the annotation system I'm using not making sense?

  • $\begingroup$ Since all the mitochondria in a cell (I'm thinking mammalian, through it may apply to others) are derived from the mother, mtDNA should all be homozygous - in fact, I don't really understand how zygosity even makes sense when talking about mitochondria. I suppose it's possible that some mtDNA in a cell is damaged or mutated, likely through the action of ROS, so there theoretically could be two (or more) "alleles" in a cell if there is a mixed population of mitochondria. I don't know quite enough about mitochondrial genetics to make this an answer, though. Just my 2 cents. $\endgroup$ – MattDMo Oct 21 '16 at 13:55
  • $\begingroup$ @MattDMo ah, I hadn't considered mized populations, that makes sense. I guess it's theoretically possible to have ~50% of mitochondria having a given variant but I would expect that to be vanishingly unlikely. If there is a variant specific to a given mitochondrion, I don't really think there would be enough sequence data to be able to call it. I guess my main question is whether mtDNA is somehow doubled in a way that makes zygosity even remotely relevant. $\endgroup$ – terdon Oct 21 '16 at 14:07
  • $\begingroup$ as far as I know, the only doubling is mtDNA replication just before a mitochondria undergoes fission. You probably want to verify that, though. $\endgroup$ – MattDMo Oct 21 '16 at 14:38

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