This tutorial provides an in depth lesson about the mtDNA and how it allows us to trace our maternal ancestry.  The lessons start off with the easy stuff like “what is mtDNA” and then advances to in depth case studies involving mtDNA.  In order to fully understand the power of mtDNA testing and its applications in ancestry, it is beneficial to understand the science behind the technology and have a good idea of how ancestry testing works and its strengths and limitations.  That’s why this tutorial consists of a number of lessons that will dissect the mtDNA, allow you to learn the details of mtDNA markers and hopefully give you a full technical understanding of how mtDNA ancestral tests work.
You don’t need to understand how mtDNA testing works in order to understand your results, but the more you know about “how”, “why” and “what’s next” when it comes to mtDNA testing, the more you will get out of your experience at Genebase.

mtDNA 101

mtDNA stands for “mitochondrial” DNA.  All of us, both males and females, carry mtDNA.  mtDNA is found in most of the cells in our body.

mtDNA is unique because while most of the DNA in our body is found in the nucleus of our cells, the mtDNA is found in small structures or organelles called “mitochondria”.  Mitochondria is found in the cytoplasm of our cells, NOT in the nucleus (remember this, because it’s important when we discuss how mtDNA is inherited).
Mitochondria is important for producing energy “ATP” for our cells.

Many copies of mtDNA are found in every mitochondria and many mitochondria are present in the cytoplasm of each cell.  That means that we have many more copies of mtDNA in our cells than other types of DNA which are present in only one set per cell.  The huge abundance of mtDNA as well as its small size makes it an excellent candidate for forensic studies of old or degraded samples.  Many archaeological studies of ancient DNA samples which are hundreds of years old focus on mtDNA testing.
Where do we get our mtDNA?  Our mtDNA comes from our mother, and our mother got her mtDNA from her mother, and so on.  The reason for the maternal inheritance pattern of mtDNA is due to its localization in the cytoplasm.  When an egg is fertilized, the cells of the resulting embryo contain the mtDNA and cytoplasm of the egg, not the sperm.  As the embryo continues to develop into a full grown human, all of the cells in the resulting human contain the cytoplasm and mtDNA of the mother.

Maternal inheritance pattern of mtDNA:
mtDNA has a very unique inheritance pattern which differs from all the other types of DNA in our body.  It is passed down along the maternal line from a mother to all of her children.  Males will carry the mtDNA of their mother, but when they have children, their children will carry the mtDNA of their own mother, not their father.  Thus, only daughters will pass the mtDNA on to future generations.  

Why does it hold ancestral information?
The maternal inheritance pattern of the mtDNA has important significance for ancestral studies.  While most of the other types of DNA in our body are mixed as they are passed down from generation to generation, the mtDNA remains unmixed because it has a strict line of descent from mother to child.  This means that our mtDNA is the same as our mother’s and our mother’s mother’s mtDNA from hundreds, even thousands of generations ago.  By testing our own mtDNA, we are in fact able to indirectly read the mtDNA genetic code of our own maternal ancestors from thousands of generations ago.
This is a brief overview of mtDNA.  Next, we will take a closer look at the mtDNA.

Facts about mtDNA

A good understanding of the background of mtDNA will help you to better understand mtDNA ancestry discussions in this tutorial.
What does mtDNA look like?
1.  Its round!  Unlike all of the other DNA in our body which are linear, mtDNA happens to be a round circle, called a “plasmid”.
2.  It’s small!  While nuclear DNA (DNA found in the nucleus of the cell) is a staggering 49,530,000 to 247,200,000 bases in length, mtDNA is only approximately 16,569 to 16,571 bases in length (don’t worry if you don’t know what a “base” is.  We will be talking about bases in more detail later in this lesson).

Why is mtDNA so different from all of the other DNA in our body?
The strange appearance of the mtDNA in comparison to the other DNA in our body has something to do with its origins.  Mitochondria has many of the same features as single cell organisms called “prokaryotes”.  Bacterial cells are prokaryotes.  The mtDNA that is found inside the mitochondria is a circular plasmid, just like the DNA in bacteria, which is also circular.  The “endosymbiotic hypothesis” suggests that the reason for the extremely close resemblance of mtDNA to bacterial DNA is that 1.7 to 2 billion years ago, mitochondria were originally bacteria that were “engulfed” by a cell and became permanently incorporated in the cytoplasm of the cell.  This is called a “symbiotic” relationship because the cell and the bacteria provided a survival advantage to each other (mitochondria produces energy “ATP” for the cell, and the cell provides protection).  This explains why the mtDNA is circular and found in the cytoplasm instead of the nucleus of the cell.
What does mtDNA do?  What’s its function?
The mtDNA contains the genetic code for 37 very important genes (13 of the genes are responsible for producing proteins, 22 of the genes hold the genetic code to produce transfer RNA (aka tRNA), and 2 genes hold the genetic code to produce ribosomal RNA (rRNA), all are necessary for our survival).  Thus, the mtDNA is very important, and when something goes wrong with the mtDNA, it can lead to mtDNA diseases such as exercise intolerance, Kearns-Syre syndrome and even death.
The 1) size, 2) structure and 3) importance of mtDNA for survival, all play a role in where ancestral markers are located in the mtDNA and will allow you to understand the testing methods used to detect ancestral markers in the mtDNA.
Next, we will discuss the different regions of the mtDNA.

mtDNA Structure

Understanding the structure of the mtDNA will help you to understand the types of ancestral markers found in it. 
mtDNA is a circular loop of DNA.  DNA is the chemical that carries genetic information.  DNA looks like a long ladder twisted into a “double helix”.  The sides of the ladder are the ”backbone”, and the rungs of the ladder consist of “nucleotide bases”.  There are 4 types of bases:  A, C, T, and G.  “A” is always connected to “T”, and “C” is always connected to “G”.

Let’s take a closer look at the mtDNA loop.  The mtDNA has 4 main regions:  1) D-Loop, 2) rRNA, 3) tRNA and 4) genes that code for protein.  The regions that code for rRNA, tRNA and protein are called the “coding region”.  The D-Loop is often referred to as the "hypervariable region".   

The mtDNA loop is 16,569 base pairs in length.  The location of each base pair in the mtDNA can be specified with an accession number according to its position in the mtDNA.  When numbering the base pairs, we start at the “origin”.  The origin is arbitrarily located in the D-Loop region.
The position of any base pair in the mtDNA is relative to the origin.  The position of any base pair in the mtDNA is designated by counting from “1″ clockwise around the mtDNA.  Thus, the positions are named 1 to 16,569 (remember this because it is important when we start talking about ancestral markers).

Let’s take a closer look at the D-Loop Region (aka Hypervariable Region) of the mtDNA since it is the region that contains the most ancestral markers and is most frequently tested for ancestral studies.
 
The D-Loop contains two regions, the HVR1 region which spans locations 16,000 to 16569, and HVR2 region which spans locations 1 to 400.  Unlike all of the other regions of the mtDNA, the D-Loop does not contain any functional genes.
Most of the ancestral markers are found in the D-Loop.  The D-Loop is considered a non-vital part of the mtDNA because it does not have a useful biological function.  Thus, whenever a mutation occurs in this region (we will discuss ancestral markers and mutations later), the individual does not die and survives to pass the mutation along to future generations.  However, the coding region of the mtDNA is considered essential for the survival of the individual, so usually, whenever a mutation occurs in this region, it is often lethal and the organism dies.  Thus, mutations which occur in the coding region are usually not passed down to future generations.  For this reason, over a period of thousands of years, many mutations accumulate in the D-Loop, but very little are found in the coding region.  Mutations are found at a much lower frequency in the coding region because only the mutations which do not end up being lethal are passed down.  When tracing ancestry, scientists usually begin by testing the D-Loop because of its abundance of mutations or “ancestral markers”.
Next, in Part 2 of this tutorial, we will talk about the ancestral markers which are found in mtDNA >>

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mtDNA and its role in ancestry. Genebase Tutorials. Retrieved March 8, 2011, from http://www.genebase.com/learning/article/17