H: An Introduction

Mitochondria are semi-independent entities found in human cells. They work to produce energy for the cell.

Mitochondrial DNA is inherited only from our mothers. Every child inherits a colony of mitochondrial DNA from their mother in her egg cell. The male sperm cell has its own mtDNA. In humans, it does not survive to be passed on.

Mitochondrial DNA is made up of a control region and a coding region. The control region is further divided into two segments. Because the control region has a higher mutation rate than the coding region the segments are called the hypervariable regions. In most journal articles hypervariable region will be abbreviated to HVR. Thus they are HVR1 and HVR2.

Mitochondrial DNA is abbreviated to mtDNA.

A mutation is a change in the mtDNA sequence. Mutations are described in terms of the first human mtDNA to be fully sequenced. Because it was sequenced at Cambridge University it is called the Cambridge Reference Sequence, CRS.

This is an example of a change at the third place in the mtDNA. The change in the sample is shown in bold.

There are are multiple ways to write this. The first is to give the position and then the change: 003C. The second is to give the normal value for CRS, the position, and then the change: T003C. When talking about a single change the second method is clearer. When describing all of the changes found in a sample though it is quicker to use the first method. Some papers place both the normal CRS value and the mutation value after the position. They then indicate the change with an arrow: 003T→C.

Most mutations to mtDNA are insertions, deletions, transitions, and transpositions.

An insertion is when an additional segment is added to the DNA sequence. Insertions are described by writing the position, a period, the insertion point and the name of the new segment. Here is an example of the common insertion 315.1C.

Insertions are highly variable. One person may have some mtDNA with an insertion and some without it.

A deletion is when a single segment is removed from the DNA sequence. Deletions are described by writing the position and a minus sign, ”-.” Here is an example of the common pair of deletions at 522 and 523.

Deletions are highly variable. Like insertions, one person may have some mtDNA with the deletion and some without it.

A transition is when one segment is changed to another of the same type.

A→G, G→A, T→C, and C→T are transitions. Here is an example of the transition A263G.

Transitions do not happen that often but they are more frequent than transpositions.

A transversion is when a segment changed to another of the opposite type.

A→T, T→A, C→G, and G→C are transpositions. Here is an example of the transversion A227T.

Transversions are uncommon.

A Haplogroup is a collection of related samples. MtDNA Haplogroups are usually defined by changes to the slower coding region. Haplogroup H is defined by two mutations, A2706A and C7028C. Because the CRS was an H, these two defining mutations will not show up on a list of coding region mutations for Hs.

Here is a typical list of coding region mutations for an H1.

A750G A1438G G3010A A4769G A8860G A15326G

This will often be written as 750G,1438G,3010A,4769G,8860G,15326G.

A haplotype is a list of the mutations for an individual in relation the the CRS. The haplotype may be the HVR regions or the entire mtDNA sequence. This is a full sequence result from GenBank, ID EF660933.

A263G 315.1C A750G A1346G A1438G G3010A G4084A A4769G G5460A T6044C A8860G T9110C A15326G C16256T T16519C

If someone were to have this sequence and test HVR1 then their haplotype would be HVR1: 16256T, 16519C.

OR

If they were to test both HVR1 and HVR2 then their haplotype would be HVR1: 16256T, 16519C; HVR2: 263G, 315.1C.

OR

If they were to test their full sequence then their haplotype would be HVR1: 16256T, 16519C; HVR2: 263G, 315.1C; CR: 750G, 1346G, 1438G, 3010A, 4084A, 4769G, 5460A, 6044C, 8860G, 9110C, 15326G.

OR

All Haplogroups interconnect forming a single tree of descent from our common foremother.

L → L1 → L3 → N → R.

R is a Macro-Haplogroup whose daughter populations span much of the Northern Hemisphere.

Based on the tree from the National Genographic Project public partition database, Behar 2007, this is a basic outline of the R Macro-Haplogroup tree.

• R {C12705C}
  • R*
  • R0* {G11719G} [aka pre-HV]
    • HV* {C14766T}
      • H {C7028C}
      • V {G4580A}
  • B {8280-}
  • R9 {3970}
  • TJ
    • T {G13368A}
    • J {A12612G}
  • U {A11467G}
    • K {A1811G,G9055A,A12308G,G12372A}