Human mitochondrial DNA haplogroup

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.^[2]

Phylogeny

This phylogenetic tree is based Van Oven (2009).^[4] In June 2022, an alternative phylogeny for haplogroup L was suggested^[5]

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

Haplogroup	Est. time of origin (kya)^[6]	Possible place of origin
L	200	Africa
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	East Africa, West Asia or South Asia
R	60	South Asia or Southeast Asia
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.^[7]

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.^[8]
HaploGrep: VCF based tool.^[9]^[10]
Haplocheck: Mitoverse's tool for both WGS and WES.^[11]
Haplotracker: A short fragment tool.^[12]
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).^[13]
HIP: Haplogroup trees.

Maps

Ancient

HIP Haplomap: Ancient uniparental map.
AH DNA: Nicky Rosenblatt's ancient uniparental map.^[14]
Ancient DNA: An aDNA map made with Map Maker.

Modern

HRAS mtDNA: A heatmap generator.

Databases

Ancient

AmtDB: An database of ancient mtDNA samples.^[15]
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.^[16]

References

^ Rishishwar L, Jordan IK (2017). "Implications of human evolution and admixture for mitochondrial replacement therapy". BMC Genomics. 18 (1): 140. doi:10.1186/s12864-017-3539-3. PMC 5299762. PMID 28178941.
^ Loogvali, Eva-Liis; Kivisild, Toomas; Margus, Tõnu; Villems, Richard (2009), O'Rourke, Dennis (ed.), "Explaining the Imperfection of the Molecular Clock of Hominid Mitochondria", PLOS ONE, 4 (12): e8260, Bibcode:2009PLoSO...4.8260L, doi:10.1371/journal.pone.0008260, PMC 2794369, PMID 20041137
^ Kivisild T (2015). "Maternal ancestry and population history from whole mitochondrial genomes". Investig Genet. 6: 3. doi:10.1186/s13323-015-0022-2. PMC 4367903. PMID 25798216.
^ ^a ^b van Oven M, Kayser M (February 2009). "Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation". Human Mutation. 30 (2): E386–94. doi:10.1002/humu.20921. PMID 18853457. S2CID 27566749.
^ Maier P, Runfeldt G, Estes R, Vilar M (2022). "African mitochondrial haplogroup L7: a 100,000-year-old maternal human lineage discovered through reassessment and new sequencing". Nature. 12 (1): 10747. Bibcode:2022NatSR..1210747M. doi:10.1038/s41598-022-13856-0. PMC 9232647. PMID 35750688. S2CID 250021505.
^ "Correcting for Purifying Selection: An Improved Human Mitochondrial Molecular Clock Supplementary" (PDF). Cell: 82–83 [89]. 2009. Archived from the original (PDF) on 2009-12-29.
^ Villems, Richard; Usanga, Esien; Mikerezi, Ilia; Gölge, Mukaddes; Claustres, Mireille; Michalodimitrakis, Emmanuel N.; Pappa, Kalliopi I.; Anagnou, Nicholas P.; Chaventré, André; Moisan, Jean-Paul; Richard, Christelle; Grechanina, Elena; Balanovska, Elena V.; Rudan, Pavao; Puzyrev, Valery; Stepanov, Vadim; Khusnutdinova, Elsa K.; Gusar, Vladislava; Balanovsky, Oleg P.; Peričić, Marijana; Barać, Lovorka; Golubenko, Maria; Lunkina, Arina; Laos, Sirle; Pennarun, Erwan; Parik, Jüri; Tolk, Helle-Viivi; Reidla, Maere; Tambets, Kristiina; Metspalu, Ene; Kivisild, Toomas; Derenko, Miroslava V.; Malyarchuk, Boris A.; Roostalu, Urmas; Loogväli, Eva-Liis (November 1, 2004). "Disuniting Uniformity: A Pied Cladistic Canvas of mtDNA Haplogroup H in Eurasia". Molecular Biology and Evolution. 21 (11): 2012–2021. doi:10.1093/molbev/msh209. PMID 15254257 – via academic.oup.com.
^ Capri, Miriam; Castellani, Gastone; Franceschi, Claudio; Lomartire, Laura; Sevini, Federica; Vianello, Dario (2013-06-12). "HAPLOFIND: a new method for high-throughput mtDNA haplogroup assignment". Human Mutation. 34 (9): 1189–1194. eISSN 1098-1004.
^ Binna, Robert; Kloss-Brandstätter, Anita; Kronenberg, Florian; Pacher, Dominic; Schönherr, Sebastian; Specht, Günther; Weissensteiner, Hansi (2010-10-19). "HaploGrep: a fast and reliable algorithm for automatic classification of mitochondrial DNA haplogroups". Human Mutaton: Variation, Informatics, and Disease. 32 (1): 25–32. eISSN 1098-1004.
^ Kronenberg, Florian; Forer, Lukas; Schönherr, Sebastian; Weissensteiner, Hansi (2023-04-23). "Haplogrep 3 - an interactive haplogroup classification and analysis platform". Nucleic Acids Research. 51 (1): 263–268. eISSN 1362-4962.
^ García-Olivares, Victor; et al. (2021-10-15) [received 2021-08-04]. "A benchmarking of human mitochondrial DNA haplogroup classifiers from whole-genome and whole-exome sequence data". Scientific Reports. 11 (20510). eISSN 2045-2322.
^ Kim, Dong-han; Kim, Kijeong; Kim, Kyung-yong; Kim, Yoonyeong; Kwon, Chulhwan (2020-04-23). "Haplotracker: a web application for simple and accurate mitochondrial haplogrouping using short DNA fragments". bioRxiv 10.1101/2020.04.23.057646v1.
^ Kayser, Manfred; van Oven, Mannis (2008-10-13). "Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation". Human Mutation. 30 (2): 386–394. doi:10.1002/humu.20921. eISSN 1098-1004.
^ Various (2017-05-30). "Rosenblatt's ancient DNA map". Anthrogenica.
^ Chyleński, Maciej; Ehler, Edvard; Juras, Anna; Moravčík, Ondřej; Novotný, Jiří; Pačes, Jan (2018-09-24). "AmtDB: a database of ancient human mitochondrial genomes". Nucleic Acids Research. 47 (D1): 29–32. eISSN 1362-4962.
^ Brown, Michael D.; Kogelnik, Andreas M.; Lott, Marie T.; Navathe, Shamkant B.; Wallace, Douglas C. (1996-01-01). "MITOMAP: A Human Mitochondrial Genome Database". Nucleic Acids Research. 24 (1): 177–179. eISSN 1362-4962.