Mitochondrial DNA is a second genome, inherited through the mother.

The genome that is not in the nucleus

Most of the DNA people mean when they say genome sits in the nucleus, wound into chromosomes. A second genome lives elsewhere, in mitochondria, the compartments that turn food into the cell's usable energy. That second genome is mitochondrial DNA, mtDNA.

You already depend on it. Muscle, brain, and heart are greedy for ATP, and mitochondria are where much of that ATP is made. The surprising part is not that cells have power stations. It is that those power stations keep a private set of instructions, a holdover from a bacterium that took up residence in another cell more than a billion years ago.

Nuclear DNA is the library. Mitochondrial DNA is a pamphlet taped to the furnace. Both are real genomes. They are not interchangeable, which is why a haplogroup on an ancestry dashboard can feel profound and still leave almost all of your inheritance untouched.

• MedlinePlus: mitochondrial DNA
• NHGRI Talking Glossary: mitochondrial DNA

About 16,500 letters and 37 genes

Human mtDNA is a circle of about 16,500 base pairs, often written 16.5 kb. MedlinePlus rounds it to about 16,500 DNA building blocks. Compare that with nuclear DNA's three billion bases and about 20,000 protein-coding genes. The mitochondrial genome is tiny, densely written, and shared in thousands of copies per cell.

Those 16,500 letters contain 37 genes, all of them needed for ordinary mitochondrial work. Thirteen encode proteins used in oxidative phosphorylation, the oxygen-using steps that make ATP. Twenty-two encode tRNA molecules and two encode rRNA molecules, the RNA helpers that assemble protein inside the mitochondrion.

The rest of the mitochondrial proteome, the hundreds of other proteins a mitochondrion needs, is encoded in the nucleus and imported in. That split is easy to miss. A mitochondrial disease can come from mtDNA, or from a nuclear gene whose protein has to travel into the mitochondrion. An ancestry haplogroup does not sort those cases.

• Size: about 16,500 base pairs, a circle
• Genes: 37, including 13 protein-coding
• Copies: hundreds to thousands of mitochondria per cell
• Nuclear DNA still encodes most mitochondrial proteins

Why the maternal line

Egg cells contribute mitochondria to the fertilized egg. Sperm cells, as a rule, do not. Children therefore inherit mtDNA from their mother, whether those children are female or male. A father does not pass his mtDNA on. A mother passes hers to every child, and only her daughters pass that line to the next generation.

That is why mitochondrial DNA is a genealogical instrument. Your mtDNA is, with rare and usually irrelevant exceptions, the mtDNA of your mother's mother's mother, as far back as the line holds. Brothers and sisters share it. Paternal cousins do not, unless they share a maternal ancestor too.

NHGRI puts the same fact without romance: offspring inherit mitochondria, and as a result mitochondrial DNA, from their mother. The romance arrives later, when a company prints a haplogroup and a migration map. The biology is the narrower claim. One parent. One line. Not the pedigree.

• How genetic inheritance works
• MedlinePlus: ancestry testing and mtDNA

Haplogroups are branches, not passports

A mitochondrial haplogroup is a named branch on the maternal tree, defined by a set of shared mtDNA variants. The labels look like catalog numbers: L, M, N, H, U, A, B, and many sub-branches. People who share a haplogroup share a maternal ancestor at some depth. The depth may be thousands of years.

That is a real historical signal. It is also a thin one. Your haplogroup does not tell you the nationality of your grandmother. It does not tell you the rest of your ancestors, the ones who contributed nuclear DNA and then left the mitochondrial line. Two neighbors can share a haplogroup and have very different autosomal ancestry.

Consumer tests sometimes sequence all of mtDNA and sometimes infer a haplogroup from a handful of chip probes. Those are different amounts of evidence. A full mtDNA sequence can place you more precisely on the tree. A few SNPs can still name a broad branch. Neither measurement is a passport, and neither is a medical workup of mitochondrial disease.

What mitochondrial DNA cannot tell you about ancestry

It cannot represent the whole family. Each generation, the nuclear genome is a shuffle of two parents. mtDNA is a copy of one. After a few generations, most ancestors have dropped off the mitochondrial line even though their nuclear DNA may still sit in you.

It cannot replace autosomal matching. Cousin matching on a genotyping chip uses hundreds of thousands of nuclear SNPs. That is how an ancestry product finds living relatives. mtDNA finds a deep maternal branch. Using one for the other's job produces confident-sounding nonsense.

It cannot settle identity questions that are social or legal. An assigned region on a map is a model built from modern reference sequences. Populations move. Names of countries change. The circle of 16,500 letters does not know the map.

• mtDNA: one maternal line, deep time, 37 genes
• Y DNA: one paternal line, only if a Y is present
• Autosomal DNA: both parents, most of the family tree
• Ethnicity estimate: a model on nuclear SNPs, not an mtDNA passport

• Ancestry DNA vs health DNA
• Chromosomes and DNA

Heteroplasmy, in one sentence, then why it matters

A person can carry a mix of slightly different mitochondrial genomes in the same cell, a state called heteroplasmy. That one fact explains a lot of the strangeness that nuclear DNA does not prepare you for.

Nuclear genes usually come in two copies. mtDNA comes in hundreds or thousands of copies, and those copies are not always identical. The fraction of altered molecules can differ between tissues, between siblings, and across a lifetime. A variant that is scarce in blood can be common in muscle. Clinical labs know to choose the tissue that matches the question.

An ancestry haplogroup test is not built to be a heteroplasmy assay. It wants a consensus maternal sequence. If a company reports a heteroplasmic site at all, it is a side observation. It is not a mitochondrial-disease diagnosis, and it is not a reason to treat a spit kit as a substitute for a specialist laboratory.

Energy, disease, and the other genome

Because those 37 genes sit in the energy machinery, some mtDNA variants cause mitochondrial disorders: problems of muscle, vision, hearing, metabolism, or the brain, depending on the variant and the heteroplasmy load. Leber hereditary optic neuropathy is a classic example tied to particular mitochondrial genes. This is specialist medicine, not a dashboard badge.

Many conditions that involve mitochondria are nuclear. The cell's power station is a joint project. A consumer haplogroup, or a handful of mtDNA SNPs on an ancestry chip, does not screen the nuclear genes that maintain mtDNA, import proteins, or run the rest of oxidative phosphorylation.

Pathogenic is still a submitted label here, as it is for nuclear variants. A ClinVar row about an mtDNA change is not a sentence about you. Frequency in the population, tissue distribution, and clinical findings still have to sit at the table. No spit-kit haplogroup replaces that.

• Mutation vs variant
• ClinVar at NCBI

What a consumer test actually measured

If your report prints a haplogroup, ask whether the lab sequenced the mitochondrial genome or inferred the branch from chip probes. The first is a small genome sequence. The second is a SNP sample. Both can be interesting. They are not the same completeness.

The rest of a typical ancestry or health kit is still nuclear: hundreds of thousands of autosomal SNPs, maybe Y markers. Mitochondrial DNA is a sidecar. It does not make the chip into a clinical mitochondrial panel, and it does not make the ethnicity estimate more true.

You can look up a named mtDNA variant as a public object the same way you look up an autosomal rsID. The identifier is not the person. Keep genotypes local. This explainer is not medical advice. If the question is illness, the path is a clinician and an assay that can see mtDNA, heteroplasmy, and the nuclear genes that belong in the differential.

• How genetic inheritance works
• How to read your DNA

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