SCIENTIFIC AMERICAN
Human
Hybrids
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DNA analyses ind that early Homo sapiens mated with
other human species and hint that such interbreeding
played a key role in the triumph of our kind
By Michael F. Hammer
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t i s h a rd to i m agi n e to day, but for most of humankind ’ s
evolutionary history, multiple humanlike species shared the earth. As
recently as 40,000 years ago, Homo sapiens lived alongside several kindred forms, including the Neandertals and tiny Homo loresiensis. For
decades scientists have debated exactly how H. sapiens originated and
came to be the last human species standing. Thanks in large part to
genetic studies in the 1980s, one theory emerged as the clear front-runner. In this view, anatomically modern humans arose in Africa and spread out
across the rest of the Old World, completely replacing the existing archaic
groups. Exactly how this novel form became the last human species on the
earth is mysterious. Perhaps the invaders killed of the natives they encountered, or outcompeted the strangers on their own turf, or simply reproduced at
a higher rate. However it happened, the newcomers seemed to have eliminated their competitors without interbreeding with them.
IN BRIEF
A long-reigning theory of the origin of Homo sapiens holds that
our species arose in a single locale—sub-Saharan Africa—and replaced archaic human species, such as the Neandertals, without interbreeding with them.
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But recent studies of modern and ancient DNA indicate that these
modern humans from Africa did mate with archaic humans and
hint that this interbreeding helped H. sapiens thrive as it colonized
new lands.
Illustration by Brian Staufer
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SCIENTIFIC AMERICAN
This Recent African Replacement model, as it is known, has
essentially served as the modern human origins paradigm for
the past 30 or so years. Yet mounting evidence indicates that it
is wrong. Recent advances in DNA-sequencing technology have
enabled researchers to dramatically scale up data collection
from living people as well as from extinct species. Analyses of
these data with increasingly sophisticated computational tools
indicate that the story of our family history is not as simple as
most experts thought. It turns out that people today carry DNA
inherited from Neandertals and other archaic humans, revealing that early H. sapiens mated with these other species and
produced fertile ofspring who were able to hand this genetic
legacy down through thousands of generations. In addition to
upsetting the conventional wisdom about our origins, the discoveries are driving new inquiries into how extensive the interbreeding was, which geographical areas it occurred in and
whether modern humans show signs of beneiting from any of
the genetic contributions from our prehistoric cousins.
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MYSTERIOUS ORIGINS
to fully appreciate the efect of these recent genetic indings
on scientists’ understanding of human evolution, we must look
back to the 1980s, when the debate over the rise of H. sapiens was
heating up. Examining the fossil data, paleoanthropologists
agreed that an earlier member of our genus, Homo erectus, arose
in Africa some two million years ago and began spreading out of
that continent and into other regions of the Old World shortly
thereafter. Yet they disagreed over how the ancestors of H. sapiens transitioned from that archaic form to our modern one, with
its rounded braincase and delicately built skeleton—features that
appear in the fossil record at around 195,000 years ago.
Proponents of the so-called Multiregional Evolution model,
developed by Milford H. Wolpof of the University of Michigan
and his colleagues, argued that the transformation occurred
gradually among archaic populations wherever they lived
throughout Africa, Eurasia and Oceania because of a combination of migration and mating that allowed beneicial modern
traits to spread among all these populations. In this scenario, although all modern humans shared particular physical features
by the end of this transition, some regionally distinctive features inherited from archaic ancestors persisted, perhaps because these traits helped populations to adapt to their local environments. A variant of Multiregional Evolution put forward
by Fred Smith, now at Illinois State University, called the Assimilation model, acknowledges a greater contribution of modern
traits by populations from Africa.
In contrast, champions of the Replacement model (also known
as the Out of Africa model, among other names), including Christopher Stringer of the Natural History Museum in London, contended that anatomically modern humans arose as a distinct
species in a single place—sub-Saharan Africa—and went on to
completely replace all archaic humans everywhere without interbreeding with them. A looser version of this theory—the Hybridization model proposed by Günter Bräuer of the University
of Hamburg in Germany—allows for the occasional production
of hybrids between these modern humans and the archaic
groups they met up with as they pushed into new lands.
With only the fossil evidence to go on, the debate seemed
locked in a stalemate. Genetics changed that situation. With the
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advent of DNA technology, scientists developed methods for
piecing together the past by analyzing genetic variation in contemporary human populations and using it to reconstruct evolutionary trees for individual genes. By studying a gene tree, researchers could infer when and where the last common ancestor
of all the variants of a given gene existed, thus yielding insights
into the population of origin for the ancestral sequence.
In a landmark study published in 1987, Allan C. Wilson of the
University of California, Berkeley, and his colleagues reported
that the evolutionary tree for the DNA found in mitochondria—
the energy-producing components of cells—traced back to a female ancestor who lived in an African population around
200,000 years ago. (Mitochondrial DNA, or mtDNA, is passed
down from mother to child and treated as a single gene in ancestry studies.) These indings it the expectations of the Replacement model, as did subsequent studies of small sections of nuclear DNA, including the paternally inherited Y chromosome.
Further genetic support for the Replacement model came a
decade later, when Svante Pääbo, now at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and
his colleagues succeeded in extracting and analyzing a fragment
of mtDNA from Neandertal bones. The study found that the
Neandertal mtDNA sequences were distinct from those of contemporary humans and that there was no sign of interbreeding
between them—a result that subsequent studies of mtDNA from
additional Neandertal specimens conirmed.
To many researchers, these ancient mtDNA indings put the
nail in the coin of the Multiregional Evolution and Assimilation
models. Others, however, maintained that their reasoning suffered from a fundamental problem. The absence of a signal for
interbreeding in any single independent region of the genome,
such as in mtDNA, does not necessarily mean that other regions
of the genome also lack signs of interbreeding. Further, any particular region of the genome that is tested could lack signs of interbreeding even if interbreeding did occur because DNA from
other species (introgressed DNA) that provided no survival advantage to H. sapiens would tend to disappear from the gene
pool over time by chance.
The best way to approach the question of whether H. sapiens
interbred with archaic species, such as the Neandertals, is thus
to compare many regions of their genomes or, ideally, their entire genomes. Yet even before such data became available for archaic humans, some early genetic studies of modern human
DNA bucked the majority trend and found data contrary to the
Replacement model. One clear example came from a 2005 study
led by Daniel Garrigan, then a postdoctoral researcher in my laboratory. Garrigan looked at DNA sequences from a nonfunctional region of the X chromosome known as RRM2P4. Analyses of
its reconstructed tree pointed to an origin for the sequence, not
in Africa but in East Asia around 1.5 million years ago, implying
that the DNA came from an archaic Asian species that intermixed with the H. sapiens originally from Africa. Similarly, that
same year our lab discovered variation in another nonfunctional
region of the X chromosome, Xp21.1, with a gene tree showing
two divergent branches that had probably been evolving in complete isolation from each other for around a million years. One of
these branches was presumably introduced into anatomically
modern populations by an archaic African species. The RRM2P4
and Xp21.1 evidence thus hinted that anatomically modern hu-
SCIENTIFIC AMERICAN
COMPETING THEORIES
Sourcing Homo sapiens
Scientists have long debated how anatomically modern humans
(dark brown lines) evolved from their archaic predecessors (light
brown lines). In the theories depicted here, modern humans
originated in Africa. According to the Replacement model, they
then replaced archaic human species throughout the Old World
without interbreeding with them. The Assimilation model, in
contrast, holds that beneicial modern features from Africa spread
among these archaic groups by a combination of steady migration
Replacement
Non-Africans
Africans
and mating among individuals known as gene low (green arrows).
The Hybridization model, for its part, posits that populations of
modern humans interbred, or hybridized (red arrows), on rarer
occasions with smaller groups of archaic species as they
encountered them. The African Multiregional Evolution model
focuses exclusively on the archaic-to-modern transition period in
Africa and argues for gene low and hybridization between
distinctive archaic groups there.
Assimilation
Non-Africans
Hybridization
Africans
Non-Africans
Africans
Extinction
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Time
African Multiregional Evolution
Modern
Archaic
Bidirectional gene flow
Unidirectional gene flow
Hybridization (introgression)
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mans mated with archaic humans from Asia and Africa, respectively, rather than simply replacing them without interbreeding.
SOURCE: MICHAEL F. HAMMER
OUR ARCHAIC DNA
more recently, advances in sequencing technology have enabled scientists to quickly sequence entire nuclear genomes—including those of extinct humans, such as Neandertals. In 2010
Pääbo’s group reported that it had reconstructed the better part
of a Neandertal genome, based on DNA from several Neandertal
fossils from Croatia. Contrary to the team’s expectations, the
work revealed that Neandertals made a small but signiicant contribution to the modern human gene pool: non-Africans today
exhibit a 1 to 4 percent Neandertal contribution to their genomes
on average. To explain this result, the researchers proposed that
interbreeding between Neandertals and the ancestors of all nonAfricans probably occurred during the limited period when these
two groups overlapped in the Middle East, perhaps 80,000 to
50,000 years ago.
Hot on the heels of the Neandertal genome announcement,
Pääbo’s team revealed an even more startling discovery. The researchers had obtained an mtDNA sequence from a piece of an
approximately 40,000-year-old inger bone found in Denisova
Cave in the Altai Mountains in Siberia. Although researchers
could not determine from the anatomy of the bone what species
Graphic by Jen Christiansen
it represented, the genome sequence showed that this individual
belonged to a population that was slightly more closely related to
Neandertals than it or Neandertals were to our species. Further,
after comparing the Denisovan sequence with its counterpart in
modern populations, the team found a signiicant amount of
DNA from a Denisovan-like population—a contribution of 1 to
6 percent—in Melanesians, Aboriginal Australians, Polynesians,
and some related groups in the western Paciic but not in Africans or Eurasians.
To explain this increasingly complex pattern of DNA sharing,
researchers proposed two interbreeding events between modern human and archaic populations: the irst, with Neandertals,
when anatomically modern humans initially migrated out of Africa; and the second, with Denisovan-like humans, when the descendants of these initial migrants made their way to Southeast
Asia. The most recent evidence, however, supports several additional interbreeding occurrences—for example, between early
modern non-Africans in the Near East that introduced genes
into the ancestors of a subset of Neandertals, and other cases in
which genes were exchanged between diferent archaic populations. The evidence also points to at least one additional event
that boosted the Neandertal contribution to contemporary populations now living in East Asia. And the previously inferred
gene low from a Denisovan-like population into modern hu-
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FINDINGS
Evidence for Interbreeding
T
The fossil record indicates that H. sapiens originated in Africa by around 200,000 years ago. DNA studies
suggest that these anatomically modern humans mated with archaic humans during migrations within
Africa and out into the rest of the Old World (gray arrows). The map shows possible ranges of archaic
species (including one identiied through a inger bone from Denisova
Cave in Siberia) and regions where interbreeding with
moderns may have occurred (ellipses). The
DNA evidence implies that several
interbreeding events left a
Denisovan
Neandertal-Denisovan
interbreeding with
signature on the genomes
interbreeding
undetermined
Neandertal
of present-day humans
species
Denisova
interbreeding
and various archaic
Cave
forms, some of which
are known to have
existed only because
of their DNA in
our gene pool.
H
Denisovan-like
Denisovan
interbreeding
interbreeding
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Archaic African
African
interbreeding
hominin interbreeding
Exact
location
uncertain
O
Possible Ranges
of Archaic Forms
R
Neandertal
Y
Denisovan or related population
Archaic African
O
H. erectus
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man populations in Melanesia is now believed to have left a
more widespread DNA signature in present-day East Asian and
Native America populations.
Although discussion of interbreeding in human evolution
typically focuses on mating between anatomically modern humans and Neandertals in Europe or other archaic forms in Asia,
the greatest opportunity for interspecies coupling would have
been in Africa, where anatomically modern humans and various
archaic forms coexisted for much longer than they did anywhere else. Unfortunately, the tropical environments of the African rain forest do not favor the preservation of DNA in ancient
remains. Without an African ancient DNA sequence to reference, geneticists are currently limited to scouring the genomes
of modern-day Africans for signs of archaic interbreeding.
To that end, PingHsun Hsieh in my laboratory aimed to test
the hypothesis of interbreeding between archaic and modern
humans in Africa without using ancient DNA from archaic human fossils. We analyzed whole genome sequence data from
two contemporary Central African Pygmy hunter-gatherer populations and identiied more than 250 genetic loci with strong
archaic DNA signals. Our inferences provided evidence for
more than a single mixing event between unidentiied African
48 | SCIENTIFIC AMERICAN | SPECIAL EDITION | AUTUMN 2016
archaic forms and anatomically modern Africans, with at least
one such event occurring within the last 30,000 years.
Another genetic hint of archaic interbreeding in Africa has
come from a study of an unusual Y chromosome sequence obtained from an African-American man living in South Carolina
whose DNA was submitted to a direct-to-consumer genetic
testing company for analysis. His particular variant had never
been seen before. Comparing his Y sequence against those of
other humans, as well as chimpanzees, my team determined
that his sequence represents a previously unknown Y chromosome lineage that increased the age of the common ancestor of
contemporary Y chromosomes. We then searched a database of
nearly 6,000 African Y chromosomes and identiied 11 matches—all of which came from men who lived in a very small area
of western Cameroon. Recently, Fernando Mendez and his
Stanford collaborators re-estimated the age of the time to the
most recent common Y chromosome ancestor at 275,000 years,
signiicantly older than the time of appearance of anatomically
modern fossils in Africa. The presence of this very ancient lineage in contemporary people is a possible sign of interbreeding
between H. sapiens and an unknown archaic species in western
Central Africa.
Map by XNR Productions
SOURCE: “GENOMIC DATA REVEAL A COMPLEX MAKING OF HUMANS,”
BY ISABEL ALVES ET AL., IN PLOS GENETICS, VOL. 8, NO. 7; JULY 19, 2012
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Recently the fossil record, too, has yielded support for the
possibility of interbreeding within Africa. Just after the publication of our results in 2011, a group of paleontologists working at
the Iwo Eleru site in Nigeria reanalyzed remains that exhibit
cranial features intermediate between those of archaic and
modern humans and determined that they date to just 13,000
years ago—long after anatomically modern H. sapiens had debuted. These results, along with similar indings from the Ishango site in the Democratic Republic of the Congo, suggest that
the evolution of anatomical modernity in Africa may have been
more complicated than any of the leading models for modern
human origins have envisioned. Either archaic humans lived
alongside modern ones in the recent past, or populations with
both modern and archaic features interbred over millennia.
genomes of people today seem to derive mostly from African
ancestors—contributions from archaic Eurasians are smaller
than either the Multiregional Evolution or Assimilation models predict.
A number of researchers now favor Bräuer’s Hybridization
model, which holds that mating between H. sapiens and archaic
species was limited to a few isolated instances. However, given
the current picture both inside and outside Africa, I favor models
in which interbreeding was more common in the history of our
species. Given the complexity of the African fossil record, which
indicates that a variety of transitional human groups, with a mosaic of archaic and modern features, lived over an extensive geographic area from Morocco to South Africa between roughly
200,000 and 35,000 years ago, I lean to a model that involves interspecies mating during the archaic-toBENEFICIAL CONTRIBUTIONS?
modern transition. Sometimes called AfriTHE ROOTS OF
detailed studies of dna regions inherited
can Multiregional Evolution, this scenario
MODERN HUMANS
from archaic ancestors will help tackle the
allows for the possibility that some of the
TRACE BACK TO NOT traits that make us anatomically modern
question of whether interbreeding (and
subsequently genetic variation) conferred
were inherited from transitional forms beJUST A SINGLE
an adaptive advantage to early H. sapiens.
fore they went extinct. To my mind, African
ANCESTRAL
Indeed, there are now several examples inMultiregional Evolution best explains gePOPULATION IN
volving archaic gene regions closely related
netic and fossil data to date.
to Neandertal and Denisovan genomes that
Before scientists can assess this model
AFRICA BUT TO
are found at particularly high frequency in
for modern human origins fully, we will
POPULATIONS
contemporary human populations. Apneed to better understand which genes
THROUGHOUT THE
proximately 10 percent of people from Eurcode for anatomically modern traits and
OLD WORLD.
asia and Oceania carry the Neandertal-like
decipher their evolutionary history. Furvariant of STAT2, which is involved in the
ther analysis of both archaic and modern
body’s irst line of defense against viral pathogens. Interesting- genomes should aid researchers in pinpointing when and
ly, it occurs at a roughly 10-fold higher frequency in Melanesia where mixing occurred—and whether the archaic genes that
than in East Asia. Analysis suggests that this DNA segment rose entered the modern human gene pool beneited the populato high frequency through positive natural selection (that is, tions that acquired them. This information will help us evalubecause it aided reproductive success or survival) rather than ate the hypothesis that interbreeding with archaic populations
merely by chance, implying that it beneited the anatomically that were well adapted to their local environments lent traits to
modern populations of Melanesia. It is not surprising to ind H. sapiens that spurred its rise to global preeminence. The
archaic contributions containing genes that function to in- sharing of genes through occasional interspecies mating is one
crease immunity. It is easy to imagine that the acquisition of a way that evolutionary novelties arise in many species of anigene variant that is adapted to fending of pathogens in non-Af- mals and plants, so it should not be surprising if the same prorican environments would immediately beneit human ances- cess occurred in our own past.
tors as they expanded from Africa into new habitats.
Many loose ends remain. Yet one thing is clear: the roots of
Perhaps the most dramatic example of shared gene variants modern humans trace back to not just a single ancestral populainvolves the gene EPAS1, involved in the body’s response to low tion in Africa but to populations throughout the Old World. Aloxygen levels. DNA sequence variants at this gene were initially though archaic humans have often been seen as rivals of modshown to confer adaptation to high altitude in Tibetans; subse- ern humans, scientists now must seriously consider the possiquently these variants were found to be inherited from a Den- bility that they were the secret of H. sapiens’ success.
isovan-like ancestor. Other examples of adaptively introgressed
genetic variants include genes involved in hair and skin biology Michael F. Hammer is a population geneticist at the University of Arizona. He studies
and lipid metabolism. Interestingly, genetic variation inherited patterns of genetic variation in modern-day populations to gain insights into the evolutionary
from Neanderthals may raise the risk of human diseases, in- origins of Homo sapiens.
cluding those associated with psychiatric, neurological, immunological and dermatological conditions.
M O R E TO E X P L O R E
In light of the accumulating evidence for interbreeding between anatomically modern H. sapiens and archaic humans
A High-Coverage Genome Sequence from an Archaic Denisovan Individual.
Matthias Meyer et al. in Science, Vol. 338, pages 222–226; October 12, 2012.
both inside Africa and beyond its conines, the Replacement
An African American Paternal Lineage Adds an Extremely Ancient Root to the
model is no longer tenable. Modern and archaic species of
Human Y Chromosome Phylogenetic Tree. Fernando L. Mendez et al. in American
Homo were able to produce viable hybrid ofspring. Thus, arJournal of Human Genetics, Vol. 92, No. 3, pages 454–459; February 28, 2013.
chaic forms could go extinct while still leaving behind their ges c i e n t i f i c a m e r i c a n . c o m /m a g a z i n e /s a
netic footprints in the modern human genome. That said, the
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