Vol.2, No.6, 571-575 (2010) Natural Science
http://dx.doi.org/10.4236/ns.2010.26072
Evolution of Homo sapiens in Asia: an alternative
implication of the “Out-of-Africa” model based on
mitochondrial DNA data
Hiroto Naora
Research School of Biology, The Australian National University, Canberra, Australia;
Received 25 September 2009; revised 9 November 2009; accepted 14 January 2010.
ABSTRACT
Cann et al. [1] have claimed on the basis of mi-
tochondrial DNA (mtDNA) data that our direct
ancestral Homo sapiens evolved in the African
continent and spread to other continents, fol-
lowed by the total replacement of the indige-
nous population. Their “Out-of-Africa” model is
based on the assumption that mtDNA inheri-
tance is simply maternal. Recent findings sug-
gest the possibility that in between-population,
e.g. African and Asian, mating, the African pa-
ternal mtDNA was transferred to the egg cell of
an Asian together with Y-chromosomal DNA in
the human past. Considering that Y-chromos-
omal DNA and mtDNA sequences of African
origin coexist together with Asian X-chromos-
omal and autosomal DNA sequences in a cur-
rent Asian, the observations by Cann et al.
suggest the full/near full replacement of mtDNA
in the human past, but do not necessarily imply
the total replacement of indigenous populations
with African migrants.
Keywords: Out-of-Africa Model; Origin of Asian;
Paternal mtDNA Inheritance; mtDNA Transmission/
Recombination
1. INTRODUCTION
Evidence has accumulated that the Homo lineage origi-
nally appeared in Africa, followed by its successful glo-
bal expansion. The view of “Out-of-Africa” that our dir-
ect ancestral H. sapiens evolved in the African continent
and spread to other continents, has been popularly re-
ceived among researchers [1-8]. On the other hand, there
have been significant fossil records in non-African con-
tinents, supporting the “regional continuity” model [9].
This model claims that our direct ancestral H. sapiens
evolved locally in the widespread regions of major con-
tinents, e.g. Africa, Europe and Asia [10-12]. In fact,
morphological continuity in East Asian traits from East
Asian Homo erectus during the middle-late Pleistocene
transition can be seen in these fossil records [12-14].
However, most of these records have neither definitely
refuted nor supported one of the models for or against
the origin of H. sapiens, particularly in Asia. Further-
more, most genetic evidence, such as simulated dendro-
grams, genetic diversity and ancient DNA sequences can
argue for either model of human origin [15].
In 1987, a crucial observation was made by Cann et
al., who examined the human mitochondrial DNA (mt
DNA) diversity of globally dispersed populations. They
concluded that modern humans simply spread to other
continents, e.g. East Asia, from Eastern Africa around
200,000 years to 50,000 years (200 KY to 50 KY) ago,
followed by the total replacement of pre-inhabited in-
digenous populations [1,2]. The “Out-of-Africa” model,
reconstructed with mtDNA data, is primarily based on a
few assumptions. One of the key assumptions is that ani-
mal mtDNA does not undergo homologous recombina-
tion. This is because of past failure to observe the clear
cases of mtDNA recombination in natural populations.
However, recent findings have raised a new insight into
mtDNA inheritance and the behaviours of mtDNA in a
fertilised egg [16,17]. In this study, an attempt was made
to integrate the interdisciplinary information obtained in
the research fields, not only anthropology and mito-
chondrial genetics but also other areas, such as devel-
opmental biology, ecology and social sciences. A meta-
analysis of these findings has raised the need of careful
scrutiny in the interpretation of Cann et al. [1,2].
2. CRITICAL VIEW OF MITOCHONDRIAL
DNA INHERITANCE: STRICTLY
MATERNAL?
Two sibling bat species, European Myotis myotis and
newly migrated M. blythii to Europe from Asia, share

H. Naora / Natural Science 2 (2010) 571-575
572
multiple identical or very similar haplotype in mitocho-
ndrial genomes when they occur in sympasy. However,
they show a strikingly different pattern of nuclear DNA
diversity. On the other hand, allopatric M. blythii in Asia
possesses mtDNA divergent from those of two species in
Europe, postulating that the mtDNA of European M.
blythii has been replaced with that of M. myotis [18].
Similar mtDNA (full/near-full/partial) replacement has
been observed in a wide variety of other species in an
animal kingdom, for example, nematodes [19], molluscs
[20], insects [21], fishes [22] and mammals other than
bats, such as vole [23]. As opposed to the popular belief,
all of these observations suggest that paternal mtDNA
inheritance occurs widely in the animal kingdom. In fact,
paternal mtDNA inheritance has been observed even in
humans [24,25]. At present, no specific information has
been reported, which strongly favours the notion that
these human cases were really exceptional and that hu-
man mtDNA replacement, similar to the cases of Myotis,
has never taken place in evolution when two “sibling”
human populations met and lived in sympasy. Further-
more, evidence has shown that the segregation and
transmission of mtDNA sequences [26-28] play a crucial
role in the inheritance of human mitochondrial diseases
[16].
Molecular and cellular events at an early stage of fer-
tilisation would also provide us with more information
which we can not ignore the view of paternal mtDNA
inheritance in human. During the process of fertilisation
in mammals, up to 100 sperm mitochondria actually
enter an egg cell, together with the sperm head [17,29,
30]. However, these paternal mtDNAs are soon de-
stroyed by a selective elimination mechanism, including
ubiquitination of paternal mitochondria [30]. However,
the elimination mechanism in the fertilised egg cell is
not always highly stringent and fails to destroy all of the
inserted paternal mitochondria, causing paternal leakage
[30]. Such leakage was observed in mice progeny at a
frequency of around one in 10,000 [31]. An interesting
observation was that when “non-self” paternal mitochon-
dria—in terms of the population/subspecies/species, to
which the mating partner belongs—are inserted into the
egg cell, such as in the mating between cow and gaur,
these mitochondria are not eliminated and remain active
in the fertilised egg cell [30]. In the mating between two
inbred mouse strains, Mus musculus and M. spretus, a
similar escape of paternal mitochondria through the eli-
mination mechanism was observed as well [32]. These
leakages would lead to a heteroplasmic offspring and
thereby enhance the opportunity of transmission or re-
combination. It has been shown that human mitochon-
drial particles are fully equipped with the toolkits re-
quired for recombination [33-35]. Furthermore, each
mitochondrial organelle holds the mechanisms, leading
from heteroplasmy to the transmission of mtDNA [16,
28]. The detailed molecular mechanisms for paternal
mtDNA inheritance and replacement might differ from
one case to the other [36] and, at present, remain to be
examined in each case.
3. THE POSSIBLE FULL/NEAR-FULL
REPLACEMENT OF MTDNA
SEQUENCES IN THE HUMAN
PAST
It is highly likely that the anatomically modern humans
that originated in Africa were different from those who
inhabited in allopasy in the Asian continent for a long
evolutionary period [37]. Furthermore, different popula-
tions have differing variation in biological responses
[38]. Therefore, African migrants and indigenous inhab-
itants in Asia were likely to show different recognition
responses to the partner’s paternal mitochondria in their
“between-population” mating although they were sibling
and hybridisable. Thus, the ubiquitin-tagged paternal
mitochondria, which were inserted in the egg cell, would
not be subject to stringent mitochondrial elimination and
could survive in the fertilised egg cell, as seen in the
case of cow and gaur pairing [30]. There would be a
huge difference in recognition response between Palaeo-
lithic African migrant and inhabited Asians, who had
never exposed to Africans and thus much more paternal
(African) mtDNA molecules might had remained active
without any damages in Asian egg cells in their “betw-
een-population” mating. Since current human populati-
ons have already mixed each other in some degree, I bel-
ieve that much more African paternal mtDNA molecules
had survived in Palaeolithic Asian egg cells than those
we suspect in current “between-population” mating.
Most, if not all, of advocates for the “Out-of-Africa”
model based on mtDNA data often argue against the
alternative model of human origine on the following
basis: The alternative model has not based on the con-
clusive evidence showing the recombination/paternal
transmission of mtDNA in the human past. However, we
should realise that the “Out-of-Africa” model has been
standing on the shaky—recently much more shaky—
ground without any explicit and conclusive evidence,
showing that any recombination/paternal transmission of
mtDNA had not taken place in the human past. In fact,
Wilson [39] has mentioned that many puzzles have re-
mained between Y-chromosome and mtDNA data in the
conservative interpretation of the complex data in human
migration. In the present paper, I have already men-
tioned the new findings, which include the paternal
mtDNA behaviours in the fertilised eggs and the recom-
bination/paternal transmission of mtDNA in the wide

H. Naora / Natural Science 2 (2010) 571-575
573
573
range of animal kingdom. In fact, taking all of these new
findings into consideration, it is much more difficult to
prepare a reasonable explanation for the notion that a
series of the events, leading to the replacement of ma-
ternal mtDNA with the paternal DNA, had never taken
place in the human past. As already mentioned, the
transmission or recombination of mtDNA in the animal
kingdom has occurred more frequently and more widely
than we have previously suspected. Therefore, the lim-
ited human cases that have been currently reported so far
on the replacement of mtDNA should not be claimed
against the argument for the possible replacement events
in the human past.
Cann et al. [1] have shown that the mtDNA itself of
current humans in the Asian continent is really of Afri-
can origin. However, their claim that indigenous inhabi-
tants in Asia became completely extinct and were totally
replaced with African migrants is confusing. As will be
discussed in the next section, the present meta-analysis
shows that ironically, their result together with chromo-
somal DNA sequences can nicely account for the possi-
ble paternal mtDNA inheritance in the human past. Thus,
this novel view does not necessarily imply the extinction
of Asian indigenous inhabitants, followed by the total
replacement of the human population in Asia.
4. DISCUSSION AND CONCLUSION
The estimated ages of the most recent common ancestor
(MRCA) of Y-chromosomal DNA sequences, such as
several sites on SRY and YAP regions, were around 150
KY ago [40]. Current non-African men carry the M168
mutation, which arose in Africa during the period of 89
KY to 35 KY ago [41-43]. All of these sequences on
Y-chromosome were much younger than those (1,860
KY to 535 KY ago) of X-chromosomal DNA sequences,
e.g. gene coded for pyruvate dehydrogenase E1α [44]
and non-coding sequences Xq [45], and autosomal DNA
sequences, e.g. gene coded for β-globin [46] and non-co-
ding sequences on chromosome 22 [47]. It should be
noted that the MRCA ages of Y-chromosomal DNA
sequences roughly correspond to the time (200 KY-100
KY ago) of human migration to Asia and thus that the
Y-chromosomal and mtDNA sequences were likely to
arise in the ancestor who lived in Africa around < 200
KY ago [2]. On the other hand, the DNA sequences on
X-chromosome and autosomes could be traced back to
the era of H. erectus in Asia [10,48-50]. Therefore, these
results clearly suggest that the current Asians would be
the offspring of the hybrids resulting from the mating
between migrated Africans and indigenous Asian in-
habitants. However, it appears likely that African mi-
grants brought only African Y-chromosomal and mt D-
NA sequences to Asia [51] and most of Asian X-chro-
mosomal and autosomal DNA sequences remained in
the hybrid offspring. The most plausible scenario of the
event in Palaeolithic Asia would be as follows: In the
“between-population” mating, African Y-chromosomal
DNA entered an Asian egg cell, accompanying with his
mtDNA. The newly inserted paternal mtDNA remained
intact without any significant damage/elimination in the
fertilised egg cell and then formed heteroplasmy in the
hybrid. After a series of transmission or recombination
processes, the maternal mtDNA of Asian origin was
fully/near-fully replaced with the paternal (African)
mtDNA. Considering the possibility that the dilution-out
and/or selective sweep of African X-chromosomal and
autosomal DNA sequences might have occurred for
evolutionary advantage, the X-chromosomal and auto-
somal DNA sequences of Asian origin would tend to be
preserved more often and finally would be maintained as
a major component in the East Asian population [52].
Therefore, the male offspring, including a current Asian
male, would not necessarily be the direct descendant of a
replaced African, but would be the hybrid offspring
possessing the mitochondrial and Y-chromosomal DNA
sequences of African origin, together with Asian X-chr-
omosomal and autosomal DNA sequences. The seque-
nce data, if possible, of chromosomal DNA and mtDNA
of Palaeolithic Asian remains and the comparison with
those of current humans in different populations should
give a brighter view on this issue. The view raised in this
paper would open a new research field of biological in-
teractions, particularly in “between-population” repro-
duction in the human past.
5. ACKNOWLEDGEMENTS
I thank Prof. D. Clark-Walker (The Australian National University) and
Dr. A. Thorne (The Australian National University) for their critical
reading of the manuscript, and valuable suggestions and conversations.
REFERENCES
[1] Cann, R.L., Stoneking, M. and Wilson, A.C. (1987) Mi-
tochondrial DNA and human evolution. Nature, 325
(6099), 31-36.
[2] Cann, R. (2001) Genetic clues to dispersal in human
populations: Retracing the past from the present. Science,
291(5509), 1742-1748.
[3] Ingman, M., Kaessmann, H., Pääbo, S., et al. (2000)
Mitochondrial genome variation and the origin of mod-
ern humans. Nature, 408(6813), 708-713.
[4] Stringer, C. (2003) Human evolution: Out of Ethiopia.
Nature, 423(6941), 692-695.
[5] White, T., Asfaw, B., de Gusta, D., et al. (2003) Pleisto-
cene Homo sapiens from Middle Awash, Ethiopia. Na-
ture, 423(6941), 742-747.

H. Naora / Natural Science 2 (2010) 571-575
574
[6] McDougall, I., Brown, F. and Fleagll, J. (2005) Strati-
graphic placement and age of modern humans from Kish,
Ethiopia. Nature, 433(7027), 733-736.
[7] Manica, A., Amos, W., Balloux, F. et al. (2007) The ef-
fect of ancient population bottle necks on human pheno-
typic variation. Nature, 448(7151), 346-349.
[8] Gibbons, A. (2009) Africans’ deep genetic roots reveal
their evolutionary story. Science, 324(5927), 575.
[9] Thorne, A.G. and Wolpoff, M.H. (1991) Conflict over
modern human origins. Search, 22, 175-177.
[10] Brooks, A.S. and Wood, B. (1990) The Chinese side of
the story. Nature, 344(6264), 288-289.
[11] Frayer, D.W., Wolpoff, M.H., Thorne, A.G., et al. (1993)
Theories of modern human origins: The palaeontological
test. American Anthropologist, 95(1), 73-96.
[12] Shang, H., Tong, H., Zhang, S., et al. (2007) An early
modern human from Tianyuan Cave, Zhoukoudian,
China. Proceedings of the National Academy of Sciences,
USA, 104(16), 6573-6578.
[13] Etler, D.A. (1994) The Chinese Hominidae: New find-
ings, new interpretations. The Ph. D. thesis, submitted to
the Graduate Division of the University of California at
Berkeley.
[14] Wu, X. and Poirier, F.E. (1995) Human evolution in
China: A metric description of the fossils and a review of
the sites. Oxford University Press, New York.
[15] Eller, E., Hawks, J. and Relethford, J.H. (2004) Local
extinction and recolonization, species effective popula-
tion size and modern human origins. Human Biology,
76(5), 689-709.
[16] Howell, N., Chinnery, P.F., Ghosh, S.S., et al. (2000)
Transmission of the human mitochondrial genome. Hu-
man Reproduction, 15(Suppl 2), 235-245.
[17] Rokas, A., Ladoukakis, E. and Zouros, E. (2003) Animal
mitochondrial DNA recombination revisited. Trends in
Ecology and Evolution, 18(8), 411-417.
[18] Berthier, P., Excoffier, L. and Ruedi, M. (2006) Reccur-
rent replacement of mtDNA and cryptic hybridization
between two sibling species Myotis myotis and Myotis
blythii. Proceedings of the Royal Society B, 273(1605),
3101-3109.
[19] Lunt, D.H. and Hyman, B.C. (1997) Animal mitochon-
drial DNA recombination. Nature, 387(6630), 247.
[20] Ladoukakis, E.D. and Zouros, E. (2001) Direct evidence
for homologous recombination in mussel (Mytilus gallo-
provincialis) mitochondrial DNA. Molecular Biology
and Evolution, 18(7), 1168-1175.
[21] Powell, J.R. (1983) Interspecific cytoplasmic gene flow
in the absence of nuclear gene flow: Evidence from
Drosophila. Proceedings of the National Academy of
Sciences, USA, 80(2), 492-495.
[22] Bernatchez, L., Glemet, H., Wilson, C.C., et al. (1995)
Introgression and fixation of arctic char (Salvelinus
alpinus) mitochondrial genome in an allopatric popula-
tion of brook trout (Salvelinus fontinalis). Canadian
Journal of Fishery and Aquatic Sciences, 52(1), 179-185.
[23] Telgelström, H. (1987) Transfer of mitochondrial DNA
from northern red-backed vole (Clethrionomys rutilus) to
bank vole (C. glareolus). Journal of Molecular Evolution,
24(3), 218-227.
[24] Hagelberg, E., Goldman, N., Liό, P., et al. (1999) Evi-
dence for mitochondrial DNA recombination in a human
population of island Melanesia. Proceedings of the Royal
Society B, London, 266(1418), 485-492.
[25] Schwartz, M. and Visssing, J. (2002) Paternal inheritance
of mitochondrial DNA. New England Journal of Medi-
cine, 347(8), 576-580.
[26] Birky, Jr, C.W., Acton, A.R., Dietrich, R., et al. (1982)
Mitochondrial transmission genetics: replication, recom-
bination and segregation of mitochondrial DNA and its
inheritance in crosses. In: Stonimski, P., Borst, P. and At-
tardi, G., Eds., Mitochondrial genes. Cold Spring Harbor
Laboratory, Cold Spring Harbor, 333-348.
[27] Hauswirth, W.W. and Laipis, P.J. (1982) Rapid variation
in mammalian mitochondrial genotypes: Implications for
the mechanism of maternal inheritance. In: Stonimski, P.,
Borst, P. and Attardi, G., Eds., Mitochondrial genes. Cold
Spring Harbor Laboratory, Cold Spring Harbor, 137-141.
[28] Hauswirth, W.W. and Laipis, P.J. (1985) Transmission
genetics of mammalian mitochondria: A molecular model
and experimental evidence. In Quagliariello, E., Slater,
E.C., Palmieri, F., Saccone, C. and Kroon, A.M., Eds.,
Achievement and perspectives of mitochondrial research.
Vol. 2: Biogenesis, Elsevier Scientific Publishers, Am-
sterdam, 49-59.
[29] Ankel-Simons, F. and Cummins, J.M. (1996) Misconcep-
tions about mitochondria and mammalian fertilization:
implications for theories on human evolution. Proceed-
ings of the National Academy of Sciences, USA, 93(4),
13859-13863.
[30] Sutovsky, P., Moreno, R.D., Ramalho-Santos, J., et al.
(2000) Ubiquitinated sperm mitochondria, selective pro-
teolysis and the regulation of mitochondrial inheritance
in mammalian embryo. Biology of Reproduction, 63(2),
582-590.
[31] Gyllensten, U., Wharton, D., Josefsson, A. et al. (1991)
Paternal inheritance of mitochondrial DNA in mice. Na-
ture, 352(6332), 255-257.
[32] Shibata, H., Hayashi, J.-I., Takahama, S., et al. (1998)
Maternal inheritance of mouse mtDNA in interspecific
hybrids: Segregation of the leaked paternal mtDNA fol-
lowed by the prevention of subsequent paternal leakage.
Genetics, 148(2), 851-857.
[33] Thyagarajan, B., Padua, R.A. and Campbell, C. (1996)
Mammalian mitochondria possess homologous DNA re-
combination activity. Journal of Biological Chemistry,
271(44), 27536-27543.
[34] Lakshmipathy, U. and Campbell, C. (1999) Double
strand break rejoining by mammalian mitochondrial ex-
tracts. Nucleic Acids Research, 27(4), 1198-1204.
[35] Lakshmipathy, U. and Campbell, C. (1999) The human
DNA ligases III gene encodes nuclear and mitochondrial
proteins. Molecular and Cellular Biology, 19(5), 3869-
3876.
[36] Zhao, X., Li, N., Guo, W., et al. (2004) Further evidence
for paternal inheritance of mitochondrial DNA in the
sheep (Ovis aries). Heredity, 93(4), 399-403.
[37] Oppenheimer, S. (2003) Out of Eden. The peopling of
the world. Constable and Robinson, London.
[38] Ashcroft, R. (2006) Race in medicine: From probability
to categorical practice. In: Ellison, G.T.H. and Goodman,
A.H., Eds., The nature of difference: Science, society and
human biology. CRC press, Boca Raton, 135-153.
[39] Wilson, J.A.P. (2008) A new perspective on later migra-

H. Naora / Natural Science 2 (2010) 571-575
575
575
tion(s). The possible recent origin of some native Ameri-
can halotypes. Critique of Anthropology, 28(3), 267-278.
[40] Hammer, M.F., Karafet, T., Rasanayagam, A., et al.
(1998) Out of Africa and back again: Nested cladistic
analysis of human Y chromosome variation. Molecular
Biology and Evolution, 15(4), 427-441.
[41] Underhill, P.A., Shen, P., Lin, A.A., et al. (2000) Y chro-
mosome sequence variation and history of human popu-
lation. Nature Genetics, 26(3), 358-361.
[42] Ke, Y., Su, B., Song, X., et al. (2001) African origin of
modern humans in East Asia: A tale of 12,000 Y chro-
mosomes. Science, 292(5519), 1151-1153.
[43] Balter, M. (2001) Anthropologists duel over modern
human origins. Science, 291(5509), 1728-1729.
[44] Harris, E. and Hey, J. (1999) X-chromosome evidence
for ancient human histories. Proceedings of the National
Academy of Sciences, USA, 96(6), 3320-3324.
[45] Kaessmann, H., Heissig, F., von Haeseler, A., et al. (1999)
DNA sequence variation in non-coding region of low re-
combination on the human X-chromosome. Nature Ge-
netics, 22(1), 78-81.
[46] Harding, R.M., Fullerton, S.M., Griffiths, R.C., et al.
(1997) Archaic African and Asian lineage in the genetic
ancestry of modern humans. American Journal of Human
Genetics, 60(4), 772-789.
[47] Zhao, Z., Jin, L., Fu, Y.-X., et al. (2000) World wide
DNA sequence variation in a 10-kilobase noncoding re-
gion on human chromosome 22. Proceedings of the Na-
tional Academy of Sciences, USA, 97(21), 11354-11358.
[48] Zhu, R.X., Potts, R., Xie, F., et al. (2004) New evidence
on the earliest human presence at high northern latitudes
in northeast Asia. Nature, 430(6999), 559-566.
[49] Dennell, R. and Roebroeks, W. (2005) An Asian perspec-
tive on early human dispersal from Africa. Nature,
438(7071), 1099-1104.
[50] Shen, G., Gao, X., Gao, B., et al. (2009) Age of Zoukou-
dian Homo erectus determined with 26Al/10B burial dat-
ing. Nature, 458(7235), 198-200.
[51] Zhang, F., Su, B., Zhang, Y.-P., et al. (2007) Genetic
studies of human diversity in East Asia. Philosophical
Transactions of Royal Society B, 362(1482), 987-995.
[52] Naora, H. (2007) Morphological variation and sexual
behaviour in the human past. II. The origin of East
Asians and their sexual behaviour. Dokkyo Journal of
Medical Sciences, 34(2), 141-151.