In 1981, a group of scientists at Cambridge University under Dr. Fred Sanger published in the journal Nature the sequence of the mitochondrial genome of one individual of European descent.
The complete sequence of the 16,569-base pair human mitochondrial genome is presented. The genes for the 12S and 16S rRNAs, 22 tRNAs, cytochrome c oxidase subunits I, II and III, ATPase subunit 6, cytochrome b and eight other predicted protein coding genes have been located. The sequence shows extreme economy in that the genes have none or only a few noncoding bases between them, and in many cases the termination codons are not coded in the DNA but are created post-transcriptionally by polyadenylation of the mRNAs.Abstract, Sequence and organization of the human mitochondrial genome, Nature 290, 457–465 (1981)
This mitochondrial DNA sequence, called the Cambridge Reference Sequence (CRS), was the original benchmark against which all other mitochondrial genomes were compared, until the corrected revised Cambridge Reference Sequence (rCRS) was published in 1999.
For many years, when mitochondrial DNA testing was used for genealogical purposes, it was measured against the rCRS and the differences noted. The Cambridge Reference Sequence was correctly criticized as being European-centric, since it requires looking both back and forward in the phylogenic tree for people around the world.
In “A ‘‘Copernican’’ Reassessment of the Human Mitochondrial DNA Tree from its Root,” published in 2012 in The American Journal of Human Genetics, researchers proposed the Reconstructed Sapiens Reference Sequence (RSRS).
Mutational events along the human mtDNA phylogeny are traditionally identified relative to the revised Cambridge Reference Sequence, a contemporary European sequence published in 1981. This historical choice is a continuous source of inconsistencies,misinterpretations, and errors in medical, forensic, and population genetic studies. Here, after having refined the human mtDNA phylogeny to an unprecedented level by adding information from 8,216 modern mitogenomes, we propose switching the reference to a Reconstructed Sapiens Reference Sequence, which was identified by considering all available mitogenomes from Homo neanderthalensis. This ‘‘Copernican’’ reassessment of the human mt DNA tree from its deepest root should resolve previous problems and will have a substantial practical and educational influence on the scientific and public perception of human evolution by clarifying the core principles of common ancestry for extant descendants.Abstract, A ‘‘Copernican’’ Reassessment of the Human Mitochondrial DNA Tree from its Root, The American Journal of Human Genetics, 90, 675–684, April 6, 2012
In spring of 2019, I tested my mitochondrial DNA with Family Tree DNA mtFull Sequence. When I received my results, they included my differences for both the RSRS and the rCRS. While I had multiple differences to the RSRS, I had only one difference with the rCRS, a heteroplasmic single nucleotide polymorphism (SNP) in the hypervariable region 2 (HVR2).
As it turns out, the Cambridge Reference Sequence is actually the sequence for mtDNA haplogroup H2a2a1. This is my mtDNA haplogroup, which I very likely share with my fore-mothers, siblings, daughters, and grandchildren.
The Family Tree DNA results showed that looking at HRV1, HVR2, and the coding regions, I had no mtDNA matches with a genetic distance of 0, 125 people with a genetic distance of 1, 241 with a genetic distance of 2, and 250 with a genetic distance of 3, for a total of 616 mtDNA matches. Of those who entered a location for their earliest known matrilineal ancestor, they listed Belgium, Bohemia (Czech Republic), Denmark, England, Finland, France, Germany, Ireland, Norway, Poland, Scotland, Slovakia, Sweden, and Wales, as well as Canada, Mexico, and the United States. With those who tested HVR1, I had 3846 Matches. For HVR1 and HVR2, I had 700 matches.
Because mitochondrial DNA changes so slowly, even exact mtDNA matches are not necessarily close relatives. I recognized one of my matches, though. He is a biologist and genetic genealogist who had presented the Basics of DNA Testing / Autosomal Testing for the Polish Genealogical Society of America (PGSA) in early 2019. His matrilineal ancestors also came from what is now Poland, and we are a match in our mtDNA hypervariable region 1 (HVR1).
- S. Anderson et al., “Sequence and organization of the human mitochondrial genome, Nature, Vol. 290, 9 April 1981. pp. 457-465.
- Richard M. Andrews et al., “Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA”, Nature Genetics, 23, 147, 1999.
- Wikipedia contributors, “Human mitochondrial DNA haplogroup,” Wikipedia, The Free Encyclopedia, https://en.wikipedia.org/w/index.php?title=Human_mitochondrial_DNA_haplogroup&oldid=884148134 (accessed June 17, 2019).
- Behar, D., van Oven, M., Rosset, S., Metspalu, M., Loogväli, E. L., Silva, N., … Villems, R. (2012). A “Copernican” Reassessment of the Human Mitochondrial DNA Tree from Its Root. American Journal of Human Genetics, 90(5), 936. doi:10.1016/j.ajhg.2012.04.007
- Family Tree DNA matches based on Build 17 from: van Oven M, Kayser M. 2009. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat 30(2):E386-E394. http://www.phylotree.org/ (Build 17)