Gene 627 (2017) 473–476

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Gene
journal homepage: www.elsevier.com/locate/gene

Review

A phylogenetic view of the Out of Asia/Eurasia and Out of Africa hypotheses MARK
in the light of recent molecular and palaeontological finds
Úlfur Árnason
Department of Brain Surgery, Faculty of Medicine, University of Lund, Lund, Sweden

A R T I C L E I N F O A B S T R A C T

Keywords: The substantiality of the Out of Africa hypothesis was addressed in the light of recent genomic analysis of extant
Human evolution humans (Homo sapiens sapiens, Hss) and progress in Neanderthal palaeontology. The examination lent no support
Human dispersal to the commonly assumed Out of Africa scenario but favoured instead a Eurasian divergence between
Askur/Embla hypothesis Neanderthals and Hss (the Askur/Embla hypothesis) and an Out of Asia/Eurasia hypothesis according to which
Out of Asia/Eurasia hypothesis, OOEH
all other parts of the world were colonized by Hss migrations from Asia. The examination suggested furthermore
Out of Africa hypothesis, OOAH
that the ancestors of extant KhoeSan and Mbuti composed the first Hss dispersal(s) into Africa and that the
Hss, Homo sapiens sapiens
Neanderthals ancestors of Yoruba made up a later wave into the same continent. The conclusions constitute a change in
Genomics paradigm for the study of human evolution.
Palaeontology
LCA, last common ancestor

1. Introduction 2. The phylogenies behind OOEH and OOAH

The Out of Africa hypothesis (OOAH), which proclaims that modern
humans (Homo sapiens sapiens, Hss) originated in Africa, is a common
assumption in the discussion of the evolution and dispersal of Hss.
Temporal estimates linked to the hypothesis have even been used to
redefine the nature of palaeontological finds related to Hss evolution.
OOAH was examined recently on the basis of palaeontology and
molecular data (Árnason, 2016). This study did not support OOAH,
proposing instead a scenario according to which Hss originated in an
Asian/Eurasian biogeographic region from which Africa was later co-
lonized. Here the Into Africa scenario is readdressed, primarily in the
light of the age and location of Neanderthal (Hsn) fossils and newly
presented genomic relationships within Hss that were not previously
available.
The Out of Asia/Eurasia hypothesis (OOEH) presented here reverses
the prevalent assumptions of Hss evolution and dispersal although the
trees underlying OOEH and OOAH are superficially the same despite
the different messages that emerge when they are examined according
to phylogenetic approaches.
It follows from the OOEH scenario that all other parts the world
were colonized by Hss populations that had their roots in Asia.
The phylogenetic Hss trees of nuclear DNA (nuDNA) and complete
mitochondrial DNA (mtDNA) molecules are generally consistent with
each other. Fig. 1 shows the main characteristics of the nuDNA tree of
Hs (Homo sapiens). The nomenclature follows Árnason (2016). Re-
garding the depicted phylogeny it should be noted that analysis of
complete mtDNAs of Neanderthals (Green et al., 2008) and Denisova
(Krause et al., 2010) place Denisova as a sister-group to a branch that
encompasses Hss and Neanderthals proper (Hsnn). The time of the di-
vergence between Hsn and Hss is commonly placed in the range of
400,000–450,000 YBP (e.g. Krause et al., 2010; Meyer et al., 2012)
relative to a Pan/Homo divergence set at 6–6.5 MYBP. In comparison
estimates based on the common external calibration point A/C-60 place
the Pan/Homo divergence at ≈7.5 MYBP (Árnason et al., 2008), re-
sulting in an Hsn/Hss divergence at ≈500,000 YBP. The estimated time
of the deepest divergence among extant humans, that between
KhoeSan/Mbuti and remaining humans, is about half that of the Hsn/
Hss split, i.e. ≈ 250,000 YBP.
An Hsn/Hss divergence ≈500,000 YBP is upheld by palaeontolo-
gical finds in Sima de los Huesos, Spain, which show that derived
Neanderthal morphological features had developed as early as
430,000 YBP (Arsuaga et al., 2014, 2015; see also the Hsn nuDNA

Abbreviations: A/C-60, the molecular calibration point implying the divergence between ruminant artiodactyls and cetaceans (whales) set at 60 million years before present; Hs, H.
sapiens, the ancestor of Hss and Hsn; Hss, H. sapiens sapiens, modern humans; Hsn, H. sapiens neanderthalensis, Neanderthals + Denisovans; Hsnd, d for Denisovans; Hsnn, n for
Neanderthals; LCA, last common ancestor; mtDNA, mitochondrial deoxyribonucleic acid; nuDNA, nuclear DNA; MYBP, million years before present; OOAH, Out of Africa hypothesis;
OOEH, Out of Asia/Eurasia hypothesis; YBP, years before present
E-mail address: ulfur.arnason@med.lu.se.

http://dx.doi.org/10.1016/j.gene.2017.07.006
Received 21 December 2016; Received in revised form 16 May 2017; Accepted 2 July 2017
Available online 05 July 2017
0378-1119/ © 2017 Published by Elsevier B.V.
Ú. Árnason Gene 627 (2017) 473–476

Table 1
Estimates of the ages of population divergences related to the OOEH scenario.

Population pairs 25% 50% 75%

Non-Africans/KhoeSan 82,000 131,000 173,000

Non-Africans/Mbuti 66,000 112,000 171,000
Non-Africans/Yoruba 45,000 63,000 123,000
Yoruba/KhoeSan 58,000 87,000 120,000
Yoruba/Mbuti 32,000 56,000 84,000

The estimates (Mallick et al., 2016) show the times at which 25%, 50% and 75% of the
lineages in each pair of populations coalesced into a common ancestral population. In the
context of the OOEH phylogeny shown in Fig. 2b the estimates are consistent with an
early KhoeSan/Mbuti dispersal into Africa followed by a corresponding migration of the
ancestors of Yoruba. The figures related to KhoeSan/Yoruba and Mbuti/Yoruba suggest
genetic exchange (probably in Asia) between Yoruba and Mbuti at a scale that exceeded
that between Yoruba and KhoeSan.

China as early as 120,000 years ago (Liu et al., 2015) also suggests that
Fig. 1. A phylogenetic tree of Homo sapiens (Hs), based on nuclear DNA. The tree includes modern humans migrated early out of Africa. Thus, early modern hu-
taxa that have particular significance for the evaluation of the Out of Africa and Out of
mans may have had the opportunity to admix with archaic hominins
Asia/Eurasia hypotheses (OOAH and OOEH). Hs encompasses the subspecies
before the migration of the modern human ancestors of present-day
Neanderthals (Homo sapiens neanderthalensis, Hsn) and modern humans (Homo sapiens
sapiens, Hss). Neanderthals proper (Hsnn) and Denisovans (Hsnd) constitute sister-groups non-Africans.”
within Hsn. KhoeSan and Yoruba represent African Hss populations, while French, Han Pagani et al. (2016) in an extensive analysis of 483 human genomes
(Chinese) and PNG (Papua-New Guinea) represent non-African taxa. The topology of the (379 new) followed Kuhlwilm et al. (2016) regarding the inclusion of
tree carries no information that allows distinction between OOAH and OOEH. Branch an Hss population that had left Africa and became extinct prior to the
lengths are not in accord with a temporal scale. The ages of the divergences between Hsn
successful expansion of Hss into Eurasia. In accord with this under-
and Hss (≈ 0.5 MYBP) and KhoeSan and its sister group (≈0.25 MYBP) have been
standing the authors concluded that > 2% of the genomes of recent
marked.
Papuans could be traced to an early Hss exodus from Africa.
Also Mallick et al. (2016) adhered to OOAH in another compre-
results of Meyer et al., 2016). The temporal limits related to the site
hensive genomic analysis that was based on 142 extant Hss populations.
might be earlier still (Bischoff et al., 2007). The exclusive occurrence of
The study included a series of pairwise comparisons related to basal Hss
Neanderthals in Europa and Asia and their absence from Africa restricts
divergences. These results have particular significance for the ex-
their origin to Eurasia (Árnason, 2016). As a consequence the origin of
amination of OOEH and OOAH, as they present an opportunity for a
their sister-group, Hss, should be placed in the same continent, i.e.
direct evaluation of the two hypotheses.
Eurasia (the Askur/Embla hypothesis, Árnason, 2016), in compliance
The study of Mallick et al. (2016) showed that the ancestral Hss
with the LCA (last common ancestor) understanding that the LCA(s) of
population had begun to develop genetic substructures > 200,000 YBP,
any two sister groups cannot be separated, neither in time nor space.
an age that is compatible with the commonly accepted estimates of the
The Eurasian palaeontological record of Hss is sparse compared to
basal divergence of extant Hss. Furthermore, the analysis demonstrated
that of Hsn. Therefore the results of Liu et al. (2015), who described the
that the basal divergence among extant Hss fell between non-Africans
presence of humans with fully modern morphologies in southern China
(as represented by a French genome) and Africans (as represented by
≈ 90,000–120,000 YBP, were highly unexpected for the adherents of
KhoeSan and Mbuti). The authors presented also estimates of several
OOAH. The authors, Liu et al. (2015), expressed in two sentences the
Hss divergences that involved Yoruba, the African population that is
essence of their findings regarding Hss evolution: “The Daoxian sample
commonly taken as constituting the founder of non-Africans. Regarding
is more derived than any other modern humans, resembling middle-to-
a potential connection between Papuans and an early OOAH dispersal
late Late Pleistocene specimens and even contemporary humans. Our
Mallick et al. (2016) concluded that indigenous Australians, New Gui-
study shows that fully modern morphologies were present in China
neans and Andamanese had the same ancestry as other non-Africans.
30,000–70,000 years earlier than in the Levant and Europe”.
Fig. 2 summarizes the phylogenies behind OOAH (2a) and OOEH
The Daoxian finds were inconsistent with OOAH, as that hypothesis
(2b) with African taxa marked in red and Eurasian in blue. The trees are
prescribed that Hss finds of this age could not exist outside Africa. The
presented in an open-book display in order to facilitate the comparison
location of the samples was also challenging as OOAH predicted that
between the two hypotheses. It can be seen that the topologies and
the Hss colonization of Eurasia should go eastward from Africa and not
taxon contents of the two trees are the same but their phylogenetic
westward from easterly Asia as maintained by Liu et al. (2015).
messages are diametrically opposed.
Kuhlwilm et al. (2016), in their comprehensive molecular study, con-
Fig. 2a is consistent with the acknowledged African split between
cluded the following regarding these palaeontological circumstances:
Hss and Hsn and an early Hsn exodus into Eurasia. This divergence was
“The recent demonstration that modern humans may have been in

Fig. 2. The phylogenies behind OOAH and OOEH.

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Ú. Árnason Gene 627 (2017) 473–476

Fig. 3. A simplified view of Hss migrations. The shaded area signifies an undefined Asian(Eurasian) area from which Hss dispersed. The red track shows the potential routes of KhoeSan,
Mbuti and Yoruba outside the Hsnn range. KhoeSan and Mbuti may have diverged before their migration into Africa. The arrow-headed lines between Mbuti and Yoruba mark potential
genetic exchange. The green track represents the common Asian origin of indigenous Australians, Papuans-New Guineans and the Andamanese (Mallick et al., 2016). The track marks also
Hsnd admixture. The blue track marks Hsnn input in European and Asian populations. Altai shows the location of the genetic contribution of Hss into Hsn (Kuhlwilm et al., 2016) and
Daoxian Cave the location of the palaeontological Hss finds described by Liu et al. (2015). (For interpretation of the references to color in this figure legend, the reader is referred to the
web version of this article.)

followed later by an African Hss divergence between KhoeSan/Mbuti
and a branch that signifies Yoruba as the ancestor of non-Africans. The
support for an African divergence between Hsn and Hss is hypothetical,
however, considering the absence of any palaeontological or archae-
ological Hsn finds in Africa. The molecular problems related to OOAH
are of a similar nature as these results have been interpreted just in
accord with the preconception of a basal Hss divergence in Africa, a
supposition that automatically followed the hypothetical placement of
the Hsn/Hss divergence in that continent.
Fig. 2b is in accord with OOEH, showing an Asian(Eurasian) di-
vergence between Hss and Hsn and a basal Asian(Eurasian) Hss diver-
gence between KhoeSan/Mbuti and a resident Hss population. The
crucial phylogenetic characteristic of the relationships is the unin-
terrupted connection (blue) between Hss and non-Africans, with the
ancestors of KhoeSan, Mbuti and Yoruba migrating to Africa. The
Eurasian placement of the divergence between Hsn and Hss is consistent
with Eurasian Neanderthal palaeontology (Arsuaga et al., 2014, 2015)
and the Askur/Embla hypothesis (Árnason, 2016).
3. The (re)orientation of early human dispersal
OOEH reverses the direction of early Hss dispersal vis-à-vis that
postulated by OOAH. The basis of OOEH is the topology shown in
Fig. 2b and the phylogenetic significance of the undisrupted connection
from the Hss branch to the non-African taxa (French, Han and PNG) as
compared to the OOAH topology in Fig. 2a.
Table 1 includes the coalescence estimates of Mallick et al. (2016)
that are connected directly to basal Hss divergences and the evaluation
of OOEH and OOAH. When these estimates are considered in light of
the phylogeny in Fig. 2b they underline that KhoeSan/Mbuti made up
the first lineage that split from the Asian(Eurasian) Hss population and
that Yoruba represents a later divergence from the same population.
The estimates in Table 1 show consistency between the deepest
estimates (estimated age of 75% coalescence) related to the divergence
between non-Africans (French) and KhoeSan (173,000 YBP) and non-
Africans and Mbuti (171,000 YBP). This agreement has become erased
at the next mark (50% coalescence) as it shows instead a non-Africans/
KhoeSan estimate of 131,000 YBP and a non-Africans/Mbuti estimate
of 112,000 YBP. These estimates indicate a markedly reduced genetic
admixture between non-Africans and KhoeSan compared to that be-
tween non-Africans and Mbuti. The same pattern emerges with respect
to the estimates of Yoruba/KhoeSan (120,000 YBP) and Yoruba/Mbuti
(84,000 YBP). Taken together the two sets of estimates suggest that
KhoeSan and Mbuti separated well before the estimated age,
131,000 YBP, of the 50% coalescence mark. The disparity between the
estimates related to KhoeSan and Mbuti may suggest that they left Asia
for Africa at different times.
Fig. 3 depicts a scenario of Hss dispersal that complies with the
phylogeny shown in Fig. 2b. The shaded area indicates the Asian pre-
sence of Hss without maintaining that a particular part of this area
should be the core of Hss distribution. The divergence between KhoeSan
and Mbuti is placed in Asia in agreement with the occurrence of genetic
admixture between Yoruba and Mbuti that is not paralleled by a cor-
responding admixture between Yoruba and KhoeSan.
The absence of Hsn contribution to the genomes of recent Africans
implies that early KhoeSan, Mbuti and Yoruba lived south of the wide
Eurasian Hsn range and that the three populations entered Africa from
the Arabian Peninsula without admixing with Hsn. The exodus from
Asia may have taken place either via a northern (Sinai) route or by
crossing the southern Red Sea at sea levels that remained low until
≈ 135,000–130,000 YBP at the end of the 2nd last glacial period (Petit
et al., 1999; Biton et al., 2008). For marking the two possibilities the
exodus of KhoeSan into Africa has been placed tentatively via a
southern route across Bab el Mandeb and that of Mbuti and Yoruba

475
Ú. Árnason
along a Sinai path. Whether KhoeSan and Mbuti took different routes
into Africa remains unknown but the estimates of Mallick et al. (2016)
may suggest that their exoduses were not contemporary.
Pagani et al. (2016) and Mallick et al. (2016) presented different
hypotheses for the origin of indigenous Australians, New Guineans and
Andamanese. Thus, Pagani et al. (2016) connected their origin with an
early exodus from Africa of a population akin to the ghost lineage in-
troduced by Kuhlwilm et al. (2016), while Mallick et al. (2016) placed
the origin with that of other non-Africans. When the two views are
considered in the context of OOEH (Fig. 2b) the lineage of indigenous
Australians, New Guineans and Andamanese becomes placed with that
of other non-Africans, as according to OOEH there was no Yoruba
coming from Africa to contribute to the ancestry of the three popula-
tions.
4. Conclusions
The existence of a continuous Hss population in Asia/Eurasia, as
shown in Fig. 2b, fits well with the palaeontological results of Liu et al.
(2015). Thus OOEH does not require the introduction of a hypothetical
out of Africa population that became extinct as proposed by Kuhlwilm
et al. (2016) as an explanation to the finds of Liu et al. (2015).
OOEH, with Asia/Eurasia as the core of Hss origin and evolution,
also widens the temporal window for accommodating the admixing of
Hss with Neanderthals and Denisovans, which is demonstrated in a
series of comprehensive molecular studies (e.g. Green et al., 2010;
Reich et al., 2010, 2011; Meyer et al., 2012; Prüfer et al., 2014; Vernot
and Akey, 2015; Sankararaman et al., 2016; Mallick et al., 2016; Vernot
et al., 2016). The hypothesis similarly extends the timespan for the
Eurasian existence of Hss and Hsn (both Hsnn and Hsnd), thereby
drawing attention to the Diring Yuriakh studies of Yuri Mochanov (e.g.
Waters et al., 1997; Carlson, 2001) with their potential early Hss and/or
Hsn presence in northern Asian regions.
The relevance of OOEH to the origin and dispersal of Hss should
promote its inclusion as an alternative to OOAH in the examination and
discussion of topics ranging from evolution, genetics and medicine, to
palaeontology, anthropology and history.
Conflict of interests
The author declares no conflict of interest.
Acknowledgments
The author thanks Prof. Eric H. Harley, Cape Town, Prof. Axel
Janke, Frankfurt am Main, Prof. Mark A. Jobling, Leicester, and Prof.
Kent Larsson, Lund, for valuable consultations during the writing of the
paper, and Mr. Stefan Andersson, Lund, for artwork. The financial
support of The Royal Physiographic Society in Lund is acknowledged,
as is also the administrative assistance of the Department of Brain
Surgery, Faculty of Medicine, University of Lund.
476
Gene 627 (2017) 473–476
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