Mitochondrial Eve

Haplogroup Modern humans
Possible time of origin	99,000 – 234,000 BP
Possible place of origin	East Africa
Ancestor	n/a
Descendants	Mitochondrial macro-haplogroups L0, L1, and L5
Defining mutations	None

In human genetics, Mitochondrial Eve is the matrilineal most recent common ancestor (MRCA), in a direct, unbroken, maternal line, of all currently living humans, who is estimated to have lived approximately 100,000–200,000 years ago. This is the most recent woman from whom all living humans today descend, in an unbroken line, on their mother’s side, and through the mothers of those mothers, and so on, back until all lines converge on one person. Because all mitochondrial DNA (mtDNA) generally (but see paternal mtDNA transmission) is passed from mother to offspring without recombination, all mtDNA in every living person is directly descended from hers by definition, differing only by the mutations that over generations have occurred in the germ cell mtDNA since the conception of the original "Mitochondrial Eve".

Mitochondrial Eve is named after mitochondria and the biblical Eve. Unlike her biblical namesake, she was not the only living human female of her time. However, her female contemporaries, excluding her mother, failed to produce a direct unbroken female line to any living person in the present day.

Mitochondrial Eve is estimated to have lived between 99,000 and 200,000 years ago, most likely in East Africa, when Homo sapiens sapiens (anatomically modern humans) were developing as a population distinct from other human sub-species.

Mitochondrial Eve lived later than Homo heidelbergensis and the emergence of Homo neanderthalensis, but earlier than the out of Africa migration. The dating for "Eve" was a blow to the multiregional hypothesis and a boost to the theory of the origin and dispersion of modern humans from Africa, replacing more "archaic" human populations such as Neanderthals. As a result, a consensus emerged among anthropologists that the latter theory was more plausible.

Analogous to the Mitochondrial Eve is the Y-chromosomal Adam, the member of Homo sapiens sapiens from whom all living humans are descended patrilineally. The inherited DNA in the male case is his nuclear Y chromosome rather than the mtDNA. Mitochondrial Eve and Y-chromosomal Adam need not have lived at the same time. For example, Y-chromosomal Adam has been estimated to have lived during a wide range of times from 180,000 to 581,000 years ago, while a 2013 paper concluded that he lived between 120,000 and 156,000 years ago (however, this paper did not include some Cameroonians and one African American, who did not inherit their Y from that "Adam").

History

Scientific research

The idea that there is a "Mitochondrial Eve", a woman from whom all people inherit their mitochondrial DNA, hinges on the theory that mutations passed down to descendants can be organized into groups. The scientific work of determining the time and place of the last woman from whom we all inherit our mtDNA was carried out by Allan Wilson, of the University of California, Berkeley, with his doctoral students Mark Stoneking and Rebecca L. Cann, using a wave of advances in genetics. Wilson had earned a worldwide recognition with his molecular clock, the technique by which species divergence time can be estimated. Inspired by the discovery of mtDNA and its unique properties, he had been motivated to employ the novel field in the study of human origin. It came to reality when Wesley M. Brown joined him as a post-doc in 1978. Brown had developed a firm grasp of restriction enzyme digestion of mtDNA from University of California, San Francisco and California Institute of Technology. The merger of two different techniques with a similar goal proved to be fruitful. In 1979 they found that mutation in mtDNA was unexpectedly fast, exhibiting 0.02 substitution per base (1%) in a million years, which means 5-10 times faster than in nuclear DNA, forming an exception in humans when compared to those of other primates including Guinea baboon, rhesus macaque, and guenon. This was the first crucial step in understanding the usefulness of mtDNA in estimating evolutionary divergence and relationships, and they soon published a paper describing the evolutionary relationships among gorillas, chimpanzees (common chimpanzee and bonobo) and humans. Strictly on the evolution of modern humans, Brown studied mitochondrial fractions from 21 individuals (placentas from labour and delivery) of different ethnicity and geographic origin. In 1980, he discovered remarkable variations among humans, and by estimating the rate of mutation, he concluded that the modern human species originated as recently as 180,000 years ago. But the shortcomings were that medical records were disassociated and he didn't know about the actual donors' ethnic backgrounds.

The study was advanced by doctoral student Rebecca L. Cann, who started collecting mtDNA in 1979 based on ethnicity. She collected samples from US hospitals from women (their placenta, to be precise) of diverse ethnic backgrounds, such as from Asia, South Pacific, Europe and Americans of African descent (she could not get samples from aboriginal Africans). Their initial observation of the mitochondrial genome of 100 individuals led them to resolve that it was possible to trace back individual female lineages back hundreds of generations thereby reaching the point of a common ancestor. However, in 1983, Cann and Wilson failed to show common ancestry from 112 individuals of different ethnic groups, and they had no indication of African samples as the oldest or the lineage of the common ancestor using an analysis called Fitch-Margoliash trees. Even in Cann's thesis in 1982, in which more elaborate estimates (including PAUP and Neighbor joining in addition to Fitch-Margoliash trees) were used, African origin of all humankind was not yet convincing, especially to Wilson, though the hunch was evident there. Prudence in Wilson was in part due to a publication of an eminent geneticist, Luigi Luca Cavalli-Sforza and his team in 1981 in which they concluded that mtDNA pointed most likely to human origin from Asia. In 1981, graduate student Mark Stoneking joined Wilson's lab for his PhD and immediately pursued Cann's work in collecting samples from aboriginal Australians and New Guineans from hospitals in Australia and New Guinea. By 1985, armed with mtDNA of 145 women of different populations, and of two cell lines, HeLa and GM 3043, derived from a Black American and a !Kung respectively, the reluctant Wilson became convinced. After more than 40 revisions of the draft, the manuscript was submitted to Nature in late 1985 or early 1986 The bombshell was eventually dropped on 1 January 1987 in Nature, in which their findings clearly showed that all current human mtDNA originated from a single population from Africa. The scientists' conclusion was that all living humans were descended from one specific woman, who lived between 140,000 and 200,000 years ago in Africa. The concept was a serious challenge to the prevailing multiregional theory, and is most parsimoniously explained by a recent African origin of modern humans, an underpinning of the so-called Out of Africa theory.

Origin of the name

Cann, Stoneking and Wilson did not use the term "Mitochondrial Eve" or even the name "Eve" in their original paper; it appears to be a catchy term popularised by the media. The name appeared in a 1987 article in Science by Roger Lewin, headlined "The Unmasking of Mitochondrial Eve." The biblical connotation was very clear from the start. The accompanying research news in Nature had the obvious title "Out of the garden of Eden." Wilson himself preferred the more euphemistic "Lucky Mother" and thought the use of the name Eve "regrettable." But the concept of Eve caught on with the public and was repeated in a Newsweek cover story (11 January 1988 issue featured a depiction of Adam and Eve on the cover, with the title "The Search for Adam and Eve"), and a cover story in Time on 26 January 1987.

Female and mitochondrial ancestry

Further information: Genetic genealogy (matrilineal), Mitochondrial DNA, and Human mitochondrial molecular clock

Through random drift or selection the female-lineage will trace back to a single female, such as Mitochondrial Eve. In this example over five generations colors represent extinct matrilineal lines and black the matrilineal line descended from mtDNA MRCA.

Simplified Human mitochondrial phylogeny

Without a DNA sample, it is not possible to reconstruct the complete genetic makeup (genome) of any individual who died very long ago. By analysing descendants' DNA, however, parts of ancestral genomes are estimated by scientists. Mitochondrial DNA (mtDNA) and Y-chromosome DNA are commonly used to trace ancestry in this manner. mtDNA is generally passed un-mixed from mothers to children of both sexes, along the maternal line, or matrilineally. Matrilineal descent goes back to our mothers, to their mothers, until all female lineages converge.

Branches are identified by one or more unique markers which give a mitochondrial "DNA signature" or "haplotype" (e.g. the CRS is a haplotype). Each marker is a DNA base-pair that has resulted from an SNP mutation. Scientists sort mitochondrial DNA results into more or less related groups, with more or less recent common ancestors. This leads to the construction of a DNA family tree where the branches are in biological terms clades, and the common ancestors such as Mitochondrial Eve sit at branching points in this tree. Major branches are said to define a haplogroup (e.g. CRS belongs to haplogroup H), and large branches containing several haplogroups are called "macro-haplogroups".

The mitochondrial clade which Mitochondrial Eve defines is the species Homo sapiens sapiens itself, or at least the current population or "chronospecies" as it exists today. In principle, earlier Eves can also be defined going beyond the species, for example one who is ancestral to both modern humanity and Neanderthals, or, further back, an "Eve" ancestral to all members of genus Homo and chimpanzees in genus Pan. According to current nomenclature, Mitochondrial Eve's haplogroup was within mitochondrial haplogroup L because this macro-haplogroup contains all surviving human mitochondrial lineages today, and she must predate the emergence of L0.

The variation of mitochondrial DNA between different people can be used to estimate the time back to a common ancestor, such as Mitochondrial Eve. This works because, along any particular line of descent, mitochondrial DNA accumulates mutations at the rate of approximately one every 3,500 years per nucleotide. A certain number of these new variants will survive into modern times and be identifiable as distinct lineages. At the same time some branches, including even very old ones, come to an end, when the last family in a distinct branch has no daughters.

Mitochondrial Eve is the most recent common matrilineal ancestor for all modern humans. Whenever one of the two most ancient branch lines dies out, the MRCA will move to a more recent female ancestor, always the most recent mother to have more than one daughter with living maternal line descendants alive today. The number of mutations that can be found distinguishing modern people is determined by two criteria: firstly and most obviously, the time back to her, but secondly and less obviously by the varying rates at which new branches have come into existence and old branches have become extinct. By looking at the number of mutations which have been accumulated in different branches of this family tree, and looking at which geographical regions have the widest range of least related branches, the region where Eve lived can be proposed.

Common misconceptions

Not the only woman

One misconception surrounding mitochondrial Eve is that since all women alive today descended in a direct unbroken female line from her, she must have been the only woman alive at the time. However, nuclear DNA studies indicate that the size of the ancient human population never dropped below tens of thousands. Other women living during Eve's time have descendants alive today but at some point in the past, each of their lines of descent did not produce a female who reproduced, thereby breaking the mitochondrial DNA lines of descent.

Not a fixed individual over time

The definition of mitochondrial Eve is fixed, but the person in prehistory who will fit this definition can change, not only because of new discoveries, but also because of unbroken mother-daughter lines coming to an end by chance. It follows from the definition of Mitochondrial Eve that she had at least two daughters who both have unbroken female lineages that have survived to the present day. In every generation mitochondrial lineages end – when a woman with unique mtDNA dies with no daughters. When the mitochondrial lineages of daughters of mitochondrial Eve die out, then the title of "Mitochondrial Eve" shifts forward from the remaining daughter through her matrilineal descendants, until the first descendant is reached who had at least two daughters who both have living, matrilineal descendants. Once a lineage has died out it is irretrievably lost and this mechanism can thus only shift the title of "Mitochondrial Eve" forward in time.

Because mtDNA mapping of humans is very incomplete, the discovery of living mtDNA lines which predate our current concept of "Mitochondrial Eve" could result in the title moving to an earlier woman. This happened to her male counterpart, "Y-chromosomal Adam," when older Y lines from Africa were discovered.

Not necessarily a contemporary of "Y-chromosomal Adam"

Sometimes mitochondrial Eve is assumed to have lived at the same time as Y-chromosomal Adam, from whom all living people are descended patrilineally, perhaps even meeting and mating with him. Even if this were true, which is currently regarded as highly unlikely, this would only be a coincidence. Like mitochondrial "Eve", Y-chromosomal "Adam" probably lived in Africa. A recent study (March 2013) concluded however that "Eve" lived much later than "Adam" – some 140,000 years later. (Earlier studies considered, conversely, that "Eve" lived earlier than "Adam".) More recent studies indicate that mitochondrial Eve and Y-chromosomal Adam may indeed have lived around the same time.

Not the most recent ancestor shared by all humans

Main article: Most recent common ancestor

Mitochondrial Eve is the most recent common matrilineal ancestor, not the most recent common ancestor. Since the mtDNA is inherited maternally and recombination is either rare or absent, it is relatively easy to track the ancestry of the lineages back to a MRCA; however, this MRCA is valid only when discussing mitochondrial DNA. An approximate sequence from newest to oldest can list various important points in the ancestry of modern human populations:

• The human MRCA. All humans alive today share a surprisingly recent common ancestor, perhaps even within the last 5,000 years, even for people born on different continents.
• The identical ancestors point. Just a few thousand years before the most recent single ancestor shared by all living humans was the time at which all humans who were then alive either left no descendants alive today or were common ancestors of all humans alive today. In other words, "each present-day human has exactly the same set of genealogical ancestors" alive at the "identical ancestors point" in time. This is far more recent than when Mitochondrial Eve lived.
• Mitochondrial Eve, the most recent female-line common ancestor of all living people.
• "Y-chromosomal Adam", the most recent male-line common ancestor of all living people.

Not the biblical Eve

Owing to its figurative reference to the first woman in the Biblical Book of Genesis, the Mitochondrial Eve theory initially met with enthusiastic endorsement from some young earth creationists, who viewed the theory as a validation of the biblical creation story. Some even went so far as to claim that the Mitochondrial Eve theory disproved evolution. However, the theory does not suggest any relation between biblical Eve and Mitochondrial Eve because Mitochondrial Eve:

• is not a fixed individual
• had a mother
• was not the only woman of her time, and
• Y-chromosomal Adam is unlikely to have been her sexual partner, or indeed to have been contemporaneous to her.

Criticism and new evidence

Soon after the watershed publication, some population geneticists criticised the analytical method as flawed, and also criticised some of the secondary conclusions while some claimed the interpretation as dubious. Alan Templeton asserted that the study did "not support the hypothesis of a recent African origin for all of humanity following a split between Africans and non-Africans 100,000 years ago" and also did "not support the hypothesis of a recent global replacement of humans coming out of Africa." This criticism was popularised into a general conception that human mtDNA analysis and the hypothesis of recent African origin are false.

Although the original research did have analytical limitations, DNA tests among African residents suggest the "Out of Africa" hypothesis still could be accurate. However they should be interpreted, estimates of the age of the last common mitochondrial ancestor continue to be refined. A recent estimate (March 2013) from the Max Planck Institute for Evolutionary Anthropology shows that Mitochondrial Eve lived about 160,000 years ago (within the reserved estimate of the original research) and also that the non-African humans were separated from Africans about 95,000 years ago. In August 2013, a study led by Stanford University School of Medicine geneticists reported the age of Mitochondrial Eve to be between about 99,000 and 148,000 years, and the Y-MRCA to have lived between 120,000 and 156,000 years ago, based on genome sequencing of 69 people from 9 different populations.

Implications of dating and placement of Eve

Further information: Multiregional origin of modern humans and Recent African origin of modern humans

There was initial resistance among some scientists to the Mitochondrial Eve hypothesis, in part because it challenged the widely accepted multiregional evolution hypothesis held by some leading paleoanthropologists, such as Milford Wolpoff. This prevailing theory held that the evolution of humanity from the beginning of the Pleistocene (2.5 million years ago) to the present day has been within a single, continuous human species, evolving worldwide to modern Homo sapiens. More resistance came from those who argued that there was too little time between Homo erectus and modern Homo sapiens to allow for another new species, and others who argued the regional evolution from archaic hominin forms into modern ones. Consequently, the finding of a recent maternal ancestor for all humans in Africa was very controversial.

Cann, Stoneking & Wilson (1987)'s placement of a relatively small population of humans in sub-saharan Africa, lent appreciable support for the recent Out of Africa hypothesis. The current concept places between 1,500 and 16,000 effectively interbreeding individuals (census 4,500 to 48,000 individuals) within Tanzania and proximal regions. Later, Tishkoff et al. (2009) using data from many loci (not just mitochondrial DNA) extrapolated that the Angola-Namibia border region near the Atlantic Ocean is likely to be near the geographical point of origin of modern human genetic diversity. In its relatively southern origin proposals, this autosomal study was considered by the authors to be broadly consistent with previous mitochondrial DNA studies, including one by some of the same authors who associated the origins of mitochondrial haplogroups L0 and L1 with "click languages" in southern and eastern Africa.

To some extent the studies have already revealed that the archaic Homo sapiens present in Northwest Africa (Jebel Irhoud) were not likely part of the contiguous modern human population. Better defined is the genetic separation among Neanderthals, Flores hobbit, Java man, and Peking man. In 1999 Krings et al. eliminated problems in molecular clocking postulated by Nei, 1992 when it was found that the mtDNA sequence for the same region was substantially different from the MRCA relative to any human sequence. Currently there are 6 fully sequenced Neanderthal mitogenomes, each falling within a genetic cluster less diverse than that for humans, and mitogenome analysis in humans has statistically markedly reduced the TMRCA range so that it no longer overlaps with Neandertal/human split times. Of all the non-African hominids, European archaics most closely resembled humans, indicating a wider genetic divide with other hominids.

Since the multiregional evolution hypothesis (MREH) revolved around a belief that regional modern human populations evolved in situ in various regions (Europe: Neandertals to Europeans, Asia: Homo erectus to East Asians, Australia: Sumatran erectines to indigenous Australians), these results demonstrated that a pure MREH hypothesis could not explain one important genetic marker.

In popular science

• Newsweek reported on Mitochondrial Eve based on the Cann et al. study in January 1988, under a heading of "Scientists Explore a Controversial Theory About Man's Origins". The edition sold a record number of copies.
• The Seven Daughters of Eve presents the theory of human mitochondrial genetics to a general audience.
• In River Out of Eden, Richard Dawkins discusses human ancestry in the context of a river of genes and shows that Mitochondrial Eve is one of the many common ancestors we can trace back to via different gene pathways.
• The Discovery Channel produced a documentary entitled The Real Eve: 6 Billion People ... from ONE Woman (or Where We Came From in the United Kingdom), based on the book The Real Eve: Modern Man's Journey Out of Africa" by Stephen Oppenheimer.

See also

• Archaeogenetics
• Coalescent theory
• Eurasian Adam
• Genealogical DNA test
• Genetic genealogy
• Haplogroup L0 (mtDNA)
• Human evolution
• Human mitochondrial DNA haplogroups
• Last universal ancestor

• Macro-haplogroup L (mtDNA)
• Mitochondrial genome
• Monogenism
• Neutral theory of molecular evolution
• Single origin hypothesis
• Timeline of evolution
• Timeline of human evolution
• Y-chromosomal Aaron
• Y-chromosomal Adam

Evolutionary tree of human mitochondrial DNA (mtDNA) haplogroups

Mitochondrial Eve (L)

L0

L1–6

L1

L2

L3

L4

L5

L6

M

N

CZ

D

E

G

Q

O

A

S

R

I

W

X

Y

C

Z

B

F

R0

pre-JT

P

U

HV

JT

K

H

V

J

T

Further reading

• *

External links

Listen to this article (info/dl)

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More spoken articles

• Krishna Kunchithapadam, "What, if anything, is a Mitochondrial Eve?" a simple explanation
• The Real Eve: Modern Man's Journey Out of Africa – by Stephen Oppenheimer – Discovery Channel, 2002