Human mitochondrial DNA haplogroup explained

In human genetics, a human mitochondrial DNA haplogroup is a haplogroup defined by differences in human mitochondrial DNA. Haplogroups are used to represent the major branch points on the mitochondrial phylogenetic tree. Understanding the evolutionary path of the female lineage has helped population geneticists trace the matrilineal inheritance of modern humans back to human origins in Africa and the subsequent spread around the globe.

The letter names of the haplogroups (not just mitochondrial DNA haplogroups) run from A to Z. As haplogroups were named in the order of their discovery, the alphabetical ordering does not have any meaning in terms of actual genetic relationships.

The hypothetical woman at the root of all these groups (meaning just the mitochondrial DNA haplogroups) is the matrilineal most recent common ancestor (MRCA) for all currently living humans. She is commonly called Mitochondrial Eve.

The rate at which mitochondrial DNA mutates is known as the mitochondrial molecular clock. It is an area of ongoing research with one study reporting one mutation per 8000 years.

Phylogeny

See also: Molecular phylogeny.

This phylogenetic tree is based Van Oven (2009).^[1] In June 2022, an alternative phylogeny for haplogroup L was suggested^[2]

• L (Mitochondrial Eve)
  • L0
  • L1-6
    • L1
    • L2-6
      • L5
      • L2'3'4'6
        • L2
        • L3'4'6
          • L6
          • L3'4
            • L4
            • L3
              • N
                • N1: I
                • N2: W
                • N9: Y
                • A
                • S
                • X
                • R
                  • R0 (FMKA pre-HV)
                    • HV: (H, V)
                  • pre-JT or R2'JT
                    • JT: (J, T)
                  • R9: F
                  • R11'B: B
                  • P
                  • U (formerly UK)
                    • U8: K
                • O
              • M
                • M9: E
                • M12'G: G
                • M29'Q: Q
                • D
                • M8: CZ (C, Z)

Major mtDNA Haplogroups

Macro-haplogroup L

Macro-haplogroup L is the most basal of human mtDNA haplogroups, from which all other haplogroups descend (specifically, from haplogroup L3). It is found mostly in Africa.

• Haplogroup L0
• L1-7
  • Haplogroup L1
  • L2-7
    • L3'4'6
      • Haplogroup L2
      • L346
        • L34
          • Haplogroup L3
          • Haplogroup L4
        • Haplogroup L6
    • L5'7
      • Haplogroup L5
      • Haplogroup L7

Macro-haplogroup M

Macro-haplogroup M is found mostly in Asia and the Americas. Its descendants are haplogroup M, haplogroup C, haplogroup Z, haplogroup D, haplogroup E, haplogroup G and haplogroup Q.

Macro-haplogroup N

Macro-haplogroup N is found mostly in Australia, the Americas and parts of Asia. Its descendants are haplogroup N, haplogroup O, haplogroup A, haplogroup S, haplogroup I, haplogroup W, haplogroup X and haplogroup Y, as well as macro-haplogroup R.

Macro-haplogroup R

Macro-haplogroup R is found mostly in Europe, Northern Africa, the Pacific and parts of Asia and the Americas. Its descendants are haplogroup R, haplogroup B, haplogroup F, haplogroup H, haplogroup V, haplogroup J, haplogroup T, haplogroup U and haplogroup K

Chronology

See also: Human mitochondrial molecular clock.

Haplogroup	time of origin ^[3]	Possible place of origin	Highest frequencies
L	200
L1-6	170	East Africa
L2-6	150	East Africa
L0	150	East Africa
L1	140	Central Africa
L3-6	130
L5	120
L2	90
L3	70	East Africa
N	70	East Africa or West Asia
M	60
R	60
U	55	North-East Africa or India (South Asia)
RT'JT	55	Middle East
JT	50	Middle East
U8	50	Western Asia
R9	47
B4	44
F	43
U4'9	42	Central Asia
U5	35	Western Asia
U6	35	North Africa
J	35
X	30
K	30
U5a	27
HV	27	Near East
J1a	27	Near East
T	27	Mesopotamia
K1	27
I	26
J1	24	Near East
W	20
U4	20	Central Asia
X2	20
H	20	Western Asia
U5a1	18	Europe
J1b	11
V	14
X2a	13	North America
H1	12
H3	12
X1	10

Geographical distribution

A 2004 paper suggested that the haplogroups most common in modern West Asian, North African and European populations were:H, J, K, N1, T, U4, U5, V, X and W.^[4]

African haplogroups: L0, L1, L2, L3, L4, L5, L6, T, U5a

Australian haplogroups: M42a, M42c, M14, M15, Q, S, O, N, P. (Refs 1, 2, 3, 4, 5, 6)

Asian haplogroups: F, C, W, M, D, N, K, U, T, A, B, C, Z, U many number variants to each section

Research software

Assignment

• mtHap: James Lick's tool (multiple input formats).
• YSEQ mt Clade Finder: FASTA based haplogroup tool. Replaced HAPLOFIND.^[5]
• HaploGrep: VCF based tool.^{[6] [7]}
• Haplocheck: Mitoverse's tool for both WGS and WES.^[8]
• Haplotracker: A short fragment tool.^[9]
• Haplogroup Finder: Ian Logan's SNP to haplogroup tool.

Dating

• mtDNA Mutation Computer Model: Ian Logan's mutation calculator.

Phylogeny

• FTDNA's mtDNA Haplotree: The largest mtDNA tree.
• YFull's MTree: An mtDNA tree. Faster loading (simpler).
• PhyloTree_mt: A traditional mtDNA tree (last updated 2016-02-18).^[10]
• HIP: Haplogroup trees.

Maps

Ancient

• HIP Haplomap: Ancient uniparental map.
• AH DNA: Nicky Rosenblatt's ancient uniparental map.^[11]
• Ancient DNA: An aDNA map made with Map Maker.

Modern

• HRAS mtDNA: A heatmap generator.

Databases

Ancient

• AmtDB: An database of ancient mtDNA samples.^[12]
• All Ancient DNA Dataset: Carlos Quiles' uniparental database (with BAM).

Modern

• GenBank mtDNA Sequence Checker: Ian Logan's GenBank based accession matching tool.
• mitoYDNA: A uniparental database.
• MITOMAP: An mtDNA genome database.^[13]

See also

• Human mitochondrial genetics
• Genetic genealogy
• Matrilineality
• Human Y-chromosome DNA haplogroups
• Population genetics

External links

• List of mtDNA haplogroup projects at ISOGG.

Notes and References

1. van Oven M, Kayser M . Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation . Human Mutation . 30 . 2 . E386–94 . February 2009 . 18853457 . 10.1002/humu.20921. 27566749 . free .
2. Maier P, Runfeldt G, Estes R, Vilar M . African mitochondrial haplogroup L7: a 100,000-year-old maternal human lineage discovered through reassessment and new sequencing . Nature . 2022 . 12 . 1 . 10747 . 10.1038/s41598-022-13856-0 . 250021505 . free . 35750688 . 9232647 . 2022NatSR..1210747M .
3. Correcting for Purifying Selection: An Improved Human Mitochondrial Molecular Clock Supplementary . 2009. 82–83 [89] . Cell . dead. https://web.archive.org/web/20091229152305/http://download.cell.com/AJHG/mmcs/journals/0002-9297/PIIS0002929709001633.mmc1.pdf . 2009-12-29.
4. Disuniting Uniformity: A Pied Cladistic Canvas of mtDNA Haplogroup H in Eurasia. Richard. Villems. Esien. Usanga. Ilia. Mikerezi. Mukaddes. Gölge. Mireille. Claustres. Emmanuel N.. Michalodimitrakis. Kalliopi I.. Pappa. Nicholas P.. Anagnou. André. Chaventré. Jean-Paul. Moisan. Christelle. Richard. Elena. Grechanina. Elena V.. Balanovska. Pavao. Rudan. Valery. Puzyrev. Vadim. Stepanov. Elsa K.. Khusnutdinova. Vladislava. Gusar. Oleg P.. Balanovsky. Marijana. Peričić. Lovorka. Barać. Maria. Golubenko. Arina. Lunkina. Sirle. Laos. Erwan. Pennarun. Jüri. Parik. Helle-Viivi. Tolk. Maere. Reidla. Kristiina. Tambets. Ene. Metspalu. Toomas. Kivisild. Miroslava V.. Derenko. Boris A.. Malyarchuk. Urmas. Roostalu. Eva-Liis. Loogväli. November 1, 2004. Molecular Biology and Evolution. 21. 11. 2012–2021. academic.oup.com. 10.1093/molbev/msh209. 15254257. free.
5. 2013-06-12 . Miriam . Capri . Gastone . Castellani . Claudio . Franceschi . Laura . Lomartire . Federica . Sevini . Dario . Vianello . HAPLOFIND: a new method for high-throughput mtDNA haplogroup assignment . 1189-1194 . Human Mutation . 1098-1004 . 34 . 9.
6. 2010-10-19 . Robert . Binna . Anita . Kloss-Brandstätter . Florian . Kronenberg . Dominic . Pacher . Sebastian . Schönherr . Günther . Specht . Hansi . Weissensteiner . HaploGrep: a fast and reliable algorithm for automatic classification of mitochondrial DNA haplogroups . 25-32 . Human Mutaton: Variation, Informatics, and Disease . 1098-1004 . 32 . 1.
7. 2023-04-23 . Florian . Kronenberg . Lukas . Forer . Sebastian . Schönherr . Hansi . Weissensteiner . Haplogrep 3 - an interactive haplogroup classification and analysis platform . 263-268 . Nucleic Acids Research . 1362-4962 . 51 . 1.
8. 2021-10-15 . received 2021-08-04 . Victor . García-Olivares . etal . A benchmarking of human mitochondrial DNA haplogroup classifiers from whole-genome and whole-exome sequence data . Scientific Reports . 2045-2322 . 11 . 20510.
9. 2020-04-23 . Dong-han . Kim . Kijeong . Kim . Kyung-yong . Kim . Yoonyeong . Kim . Chulhwan . Kwon . Haplotracker: a web application for simple and accurate mitochondrial haplogrouping using short DNA fragments . 10.1101/2020.04.23.057646v1.
10. 2008-10-13 . Manfred . Kayser . Mannis . van Oven . Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation . 386-394 . 10.1002/humu.20921 . Human Mutation . 1098-1004 . 30 . 2. free .
11. Web site: 2017-05-30 . Various . Rosenblatt's ancient DNA map . Anthrogenica.
12. 2018-09-24 . Maciej . Chyleński . Edvard . Ehler . Anna . Juras . Ondřej . Moravčík . Jiří . Novotný . Jan . Pačes . AmtDB: a database of ancient human mitochondrial genomes . 29-32 . Nucleic Acids Research . 1362-4962 . 47 . D1.
13. 1996-01-01 . Michael D. . Brown . Andreas M. . Kogelnik . Marie T. . Lott . Shamkant B. . Navathe . Douglas C. . Wallace . MITOMAP: A Human Mitochondrial Genome Database . 177-179 . Nucleic Acids Research . 1362-4962 . 24 . 1.