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Mitochondrial DNA Tutorial

What is mtDNA?

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.

Most of the DNA in our body is found in the nucleus of our cells, but mtDNA is unique, as it is found in small structures or organelles called mitochondria. Mitochondria are found in the cytoplasm of our cells, NOT in the nucleus.

Multiple mtDNA copies in each of our cells

Many mtDNA copies are found in every mitochondria, and there are many mitochondria present in the cytoplasm of each cell. This means that we have many more copies of mtDNA in our cells than nuclear DNA, which is present in only one set per cell. The huge abundance of mtDNA, as well as its small size, make it an excellent candidate for forensic studies of old or degraded samples.

 

mtDNA has a unique inheritance pattern

Most of our DNA is inherited in equal proportions from each of our parents – one copy of each chromosome from each parent. But mtDNA has a unique inheritance pattern. We inherit all our mtDNA from our mother, and our mother inherited all her mtDNA from her mother, and so on. It is passed down strictly along the direct 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 pass the mtDNA on to future generations.

The reason for the maternal inheritance pattern of mtDNA is due to its localization in the cell. When an egg is fertilized, the cells of the resulting embryo contain the cytoplasm of the egg, not the sperm. Since mtDNA is found only in the cytoplasm, all of our mtDNA comes from our mother, not our father. As the embryo continues to develop into a full grown human, all of the cells in the resulting human contain strictly the cytoplasm and mtDNA of the mother, not the father.

How does mtDNA hold maternal ancestral information?

The maternal inheritance pattern of the mtDNA has important significance for ancestral studies. While most of the other DNA in our body is mixed from generation to generation, mtDNA remains unmixed because it follows a strict single 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, back thousands of generations. mtDNA testing allows us to trace our direct maternal lineage (mother’s mother’s mother’s….. maternal lineage).

Facts about mtDNA

A good understanding of the basics of mtDNA helps you to better understand mtDNA ancestry discussions in this tutorial.

What does mtDNA look like?

1. It’s round! Unlike our nuclear DNA, which is linear, mtDNA is a round circle, called a plasmid.

2. It’s small! While nuclear DNA is a ~247,200,000 bases pairs, mtDNA is only ~16,569 base pairs. Don’t worry if you don’t know what a base pair is – we will be talking about base pairs in more detail later in this tutorial.

 

Why is mtDNA so different from the other DNA in our body?

The strange appearance of mtDNA in comparison to the other DNA types in our body has something to do with its ancient 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.

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 free-living 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 small and circular and found in the cytoplasm instead of the nucleus of the cell.

What does mtDNA do?

mtDNA contains the genetic code for at least 37 essential genes. 13 of the genes are responsible for producing proteins, 22 of the genes hold the genetic code to produce transfer RNA (tRNA), and two genes encode ribosomal RNA (rRNA). Thus, the mtDNA is very important, and when something goes wrong with the mtDNA, it can lead to mtDNA diseases, such as exercise intolerance or Kearns-Syre syndrome.

The size, structure and importance of mtDNA for survival, all play a role in where the majority of ancestral markers are located in the mtDNA.

mtDNA structure

mtDNA is a circular loop of DNA. 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 four types of bases: T, C, A and G. T is always paired to A, and C is always paired to G. This pairing leads to the term “base pairs”.

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. When numbering the base pairs, we start at the “origin”. The origin is arbitrarily located in the D-loop between the HVR1 and HVR2 regions.

mtDNA contains three different regions

The mtDNA genome can be divided into three main regions: HVR1, HVR2 and the Coding Region. The HVR1 region is ~500 nucleotides, the HVR2 region is ~600 nucleotides, and the coding region is ~15,500 nucleotides.

 

The HVR1 and HVR2 regions of the mtDNA contain the most variation, and are the most common starting point for maternal ancestral studies. The HVR1 and HVR2 regions are considered non-vital parts of the mtDNA, because they do not have a useful biological function. Thus, when a change (mutation) occurred in the HVR1 or HVR2 region of one of our ancestors, the individual did not die, and survived to pass the mutation along to all future generations.

In contrast, the coding region contains many essential genes, so when a mutation occurs in the coding region, it is often lethal. Thus, very few mutations in the coding region are passed down to future generations. For this reason, over tens of thousands of years, many mutations have accumulated in the HVR1 and HVR2 regions, but a much smaller number are found in the coding region. When tracing ancestry, scientists usually begin by testing the HVR1 and HVR2 regions because of their small sizes and abundance of mutations.

What variation occurs in the mtDNA?

There are many types of mutations, but the type of mutation most commonly found in mtDNA is called a “SNP” (single nucleotide polymorphism). A SNP occurs when a single nucleotide is replaced with a different nucleotide. For example, in this diagram, the “T” at location 40 is replaced by a “G”.

 

This mutation is documented as follows:

Location: 40

Nucleotide Change: T>G (also indicated as T40G)

When you test your mtDNA, your results report will document the SNPs that you carry in your mtDNA. These are all variations from the revised Cambridge Reference Sequence.

What is the revised Cambridge Reference Sequence?