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Mitochondrial DNA

Each mitochondrion has its own DNA, or genome, separate from the DNA in the nucleus.   The mitochondrial genome is a circular molecule of double-stranded DNA, 16,569 base pairs long.  A base is a specific component of the DNA and is made of adenine, thymine, guanine or cytosine (A, T, G, C). Within the genome, there is an approximately 1100 base long regulatory region, called the D-loop.  Because this region accumulates genetic changes faster than the rest of the genome, it is also referred to as the hypervariable region.  The remainder of the mitochondrial genome is coding DNA - it is copied into RNA molecules that perform downstream functions within the cell.  The mitochondrial genome codes for 13 proteins (used in energy production by the mitochondria) two ribosomal RNAs (used for protein synthesis) and 22 transfer RNAs (also used for protein synthesis).  A representation of a mitochondrial genome can be found here.

Mitochondrial DNA is inherited only from the mother: the fertilized egg destroys the mitochondria of the sperm. Because of this selective matrilineal transmission, mitochondrial DNA sequences can be used to by population geneticists and evolutionary biologists to shed light on the unbroken genetic line connecting us to our maternal ancestors.

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How mtDNA is inherited

Note that the children inherit their maternal grandmother's mitochondrial DNA (in purple, left side of diagram) without contribution from their grandfather or father. 

Polymorphisms

Mutations, when they occur, are passed down to the children*.  These mutations, or polymorphisms, tell a story about your past.  Part of that story is told simply by the number of polymorphisms identified in your mtDNA.  Because the genome accumulates mutations at a linear rate over time, the polymorphisms represent a sort of molecular clock: the more polymorphisms that differ between two people's mtDNA, the longer ago in the past they shared a common ancestor.  For example, while an African-American and a European might have 75 variable polymorphisms, two people of European descent might have only 25 variable polymorphisms, reflecting a more recent common ancestor.

      Your polymorphisms also tell a story about place, about where your ancestors came from.  Imagine a small group of people, migrating out of the Middle East and into a locale somewhere in Western Europe.  If they succeed in colonizing the region, they will pass on their particular mtDNA onto their descendants.  Skipping forward to today, these polymorphisms can now be associated with particular geographic areas and populations. In conjunction with linguistic and anthropological studies, researchers have constructed ancient migration patterns based on the presence of these polymorphisms in human populations. 

     After completion of your sequencing project, the sequence of your mtDNA is compared to an industry standard, called the revised Cambridge Reference Sequence, or rCRS.  (The original had several mistakes, thus the awkward appellation).  The rCRS sets the numbering for each base, so that any two mtDNAs can be compared.  This is important because, due to small deletions and insertions of DNA in many genomes, any two genomes would quickly become out of register.  To get the numbering right, each genome is first aligned to the standard rCRS, introducing gaps or insertions as needed, and then each of the 16,569 or so paired bases is numbered relative to the standard genome. Polymorphisms are generally written like this: "A750G", which means that the A at position 750 in the rCRS is changed to a G in the equivalent spot on the sample genome. 

     Some polymorphisms are quite common, represented in over 50% of a given population.  This may be due to a founder effect, as mentioned above.  There is also some evidence that certain polymorphisms may have rendered their carriers resistant to certain diseases, giving them a selective advantage over non-carriers. A recent article published in Lancet, for example, claims that mtDNA haplogroup H is a strong independent predictor of  increased chance of survival after sepsis, and goes on to suggest that this resistance may have contributed to making this haplogroup the most common on Europe.  There are also studies of which polymorphisms are more likely to be found in centenarians, for example Zhang, et al.

Other polymorphisms are quite rare, occurring only once in a thousand or more mitochondrial genomes.  There are still relatively few full length genome available for comparison, however; the actual frequency of a given polymorphism will be better known as more and more genomic sequences become available.  The words polymorphism and mutation are often used interchangeably in talking about mt DNA.  One way to distinguish them is that a mutation becomes a polymorphism as it gains a foothold within a population.  If you inherit a change in your mitochondrial DNA that originated in your mother's egg, that is a mutation, defined as a genetic alteration that occurs during transmission of a gene from one generation to the next.  If after some number of generations your descendants still carry this alteration and they come to represent a significant proportion of the population, say over 1%, the alteration can be called a polymorphism, in the sense that it is one of the variant types found in the pool of mitochondrial genomes.  Mitochondria have been around for over a billion years.  They are clearly very well-adapted and most mutations will be lost after a few generations.  If, on the other hand, the mutation confers some sort of survival benefit in a given environment, as in the sepsis story referred to above,  they are more likely to make the leap from a mutation in one person to a polymorphism within the wider population.  More detailed information about specific polymorphisms is available here.

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Haplogroups

Your haplogroup identifies your ethnic and geographic origins on your maternal line.  Haplogroups are defined by polymorphisms, as shown in the diagram below.  If upon comparing your mitochondrial to the standard sequence, polymorphisms are identified at positions 2706 and 7028, you will be classed in haplogroup H.  If you also have polymorphisms at positions 16519, 6776,  152, 13404 and 16239, you can be more precisely placed within the sub-haplogroup H3a.  The key concept of phylogenetic trees is that the haplogroups share a common ancestor.  The mitochondrial genomes of every member of haplogroup H, for example, are derived from a single founder "mother" that lived around 9,000 years ago.  There are around nine main haplogroups in Europe, and about 30 worldwide.  Much more detail about individual haplogroups is provided here and on the certificate sent with your results.

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Mitochondrial Eve

All of the mitochondrial haplogroups coalesce into a single founder genome at a time about 160,000 years ago.  There are a couple of things we can say about the woman who has the distinction of having copies of her mitochondrial genome present is every person living today. She lived in Africa, so on some level we are all Africans.  She had at least two daughters: if she just had one, then that daughter would be our most recent common mitochondrial ancestor, not her mother.  This last point suggests the essentially mathematical argument for the existence of this founding mother.  Here is the proof that she had to exist: Let's say there are 6 billion people alive today and that the average family has two boys, two girls, a mother and a father.  How many are mothers?  Well, one in six, or 1 billion.  How many mothers were there in the previous generation?  Each of our 1 billion mothers was once a child in a family with two girls and two boys (we don't care about the boys since mtDNA is transmitted only via the female line).  For each two girls, there was one mother, thus the number of grandmothers is 500 million.  You can see that for each generation we have fewer mothers.  Eventually the sequential halving comes to its mathematically predestined end and we are left with a single person, our "Mitochondrial Eve".  It is important to note that there was in all probability nothing special about her - she was a member of a clan that included women much like her.  Her founder status is a matter of chance, it could just  as easily been another woman.  In the unlikely case that our Mitochondrial Eve enjoyed an exalted relationship with her Creator, as did her biblical namesake, it has been lost in time.

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Phylogenetic Tree

A phylogenetic tree, like a family tree, traces diverging lines of descent from a common ancestor. The phylogenetic tree of mtDNA is, remarkably, the evolutionary history of a single molecule.  The scientific claims underlying the tree are remarkable, even startling - every person alive today inherited their mitochondrial DNA from a single woman who lived over 16 centuries ago.  There are millions of different mitochondrial genomes in the world today, all derived from that progenitor.  The differences between genomes reflect random inherited mutations, or polymorphisms.  Polymorphisms are used to define the different branches of the tree - "Everyone with polymorphism X goes in this bin here", and so on.  The cluster of people with a similar spectrum of polymorphisms is a haplogroup.  Each person's individual set of polymorphisms is their haplotype.

* Actually, mutations are passed down only under a special set of circumstances: the mutation has to occur in a woman; it must take place in the special type of cell that gives rise to oocytes (eggs); the egg carrying the mutated mtDNA must be fertilized by an X-bearing sperm (to produce a girl); and the embryo must develop into a female adult, who can then pass it on to her children.

* Actualy, mutations are passed down only under a special set of circumstances: the mutation has to occur in a woman; it must take place in the special type of cell that gives rise to oocytes (eggs); the egg carrying the mutated mtDNA must be fertilized by an X-bearing sperm (to produce a girl); and the embryo must develop into a female adult, who can then pass it on to her children.

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