Denisovan Ancestry in Papua New Guinea (PNG)

An excavation in Denisova cave in Siberia, Russia, where remains of Denisovan hominins were first discovered.

The first Neanderthal1 and the Denisovan2 genome sequences revolutionized the study of ancient human history, not least because they showed that these groups interbred with anatomically modern humans, contributing to the genetic diversity of many people alive today. All humans whose ancestry originates outside of Africa owe about 2% of their genome to Neanderthals; and certain populations living in Oceania, such as Papua New Guineans and Australian Aboriginals, got about 4% of their DNA from interbreeding between their ancestors and Denisovans, who are named after the cave in Siberia’s Altai Mountains where they were discovered. The cave contains remains deposited there between 30,000 and 50,000 years ago. Those conclusions however were based on low-quality genome sequences, riddled with errors and full of gaps, David Reich, an evolutionary geneticist at Harvard Medical School in Boston, Massachusetts said at the meeting. His team, in collaboration with Svante Pääbo at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, have now produced much more complete versions of the Denisovan and Neanderthal genomes — matching the quality of contemporary human genomes. The high-quality Denisovan genome data and new Neanderthal genome both come from bones recovered from Denisova Cave.


Proportion of alleles shared with the Neandertal and Denisovan genomes for the Tianyuan and present-day individuals. The x axis shows the percent of alleles that match the Neandertal and Denisovan genomes at sites where both of these differ from seven Africans, and the y axis indicates the percent of alleles that match the Denisovan genome where this differs from the Neandertal as well as from the seven Africans.

The new Denisovan genome indicates that this enigmatic population got around: Reich said at the meeting that they interbred with Neanderthals and with the ancestors of human populations that now live in China and other parts of East Asia, in addition to Oceanic populations, as his team previously reported. Most surprisingly, Reich said, the new genomes indicate that Denisovans interbred with another extinct population of archaic humans that lived in Asia more than 30,000 years ago, which is neither human nor Neanderthal. The meeting was abuzz with conjecture about the identity of this potentially new population of humans. “We don’t have the faintest idea,” says Chris Stringer, a paleoanthropologist at the London Natural History Museum, who was not involved in the work. He speculates that the population could be related to Homo heidelbergensis, a species that left Africa around half a million years ago and later gave rise to Neanderthals in Europe. “Perhaps it lived on in Asia as well,” Stringer says.

Nature doi:10.1038/nature.2013.14196



PCA of archaic ancestry under a serial founder model with (or without) archaic admixture. PCA was performed by projecting hypothetical extant humans onto the variation of a hypothetical chimpanzee and two hypothetical archaic hominins that shared a recent history with modern humans ∼400 kya. (A) A model with no admixture between colonizing and archaic populations. (B) A model with two separate admixture events: from archaic population A into colony 25 (forward in time, 2.5% of colony 25 is replaced) and from archaic population B into colony 97 (forward in time, 5% of colony 97 is replaced). This model is similar to the model suggested in ref. 24 (Fig. 1A). (C) A model with the two admixture events in B and an additional admixture event from archaic population B into colony 75 (forward in time, 1% of colony 75 is replaced). D–F show PCA results from models A, B, and C, respectively. G–I show PCA results for models A, B and C, respectively, but with SNPs with minor allele frequency (MAF) < 5% excluded. In D–I, we display the mean PC loading of 10 samples from each colony numbered and colored according to distance from the founding population. The model in C produced the qualitatively most similar result compared with the empirical data in Fig. 1B.

We recovered the previously reported (24) pattern—that extant human variation is largely organized in three clusters corresponding to Africans, Oceanians, and other non-Africans, respectively (Fig. 1B and Fig. S1). In the worldwide collection of extant populations, we used Procrustes superimposition (45) to compare PC1 and PC2 with geographic coordinates (longitude and latitude) for each population and found that sampling location was mirrored, to some extent, by archaic ancestry (individuals: Procrustes correlation = 0.127, P << 10−6; population means: Procrustes correlation = 0.309, P < 0.01). This pattern was expected given a model with two episodes of archaic gene flow involving non-Africans and Oceanians (Fig. 2B) (23, 24). However, PC1 and PC2 were also correlated with geography in a region comprising Eurasia and the Americas (individuals: Procrustes correlation = 0.104, P < 10−4; population means: Procrustes correlation = 0.335, P = 0.017), which seemed incompatible with previously suggested admixture scenarios postulating that archaic ancestry is homogeneous in people of European, Asian, and Native American descent (23, 24).

By comparing the geographic locations of individuals from different regions with the archaic ancestry signal (PC1 values), East Asian (two-sided t test: P < 10−6) and Native American (P < 10−8) populations were found to be more similar to archaic hominins compared with European and Central/South Asian populations (Fig. 1B and Table S1). In addition, the archaic ancestry signal was positively correlated with distance from East Africa (individuals: Spearman's rank correlation coefficient rs = 0.189, P < 10−9; population means: rs = 0.600, P < 10−4) (Fig. 1C). Because it is well-known that PCs of modern human genetic variation capture geography to some extent (35, 46), we also computed PCs using modern human genetic variation in Eurasia (SI Results) and found that the top two PCs of differentiation between Europe and East Asia were correlated with the archaic ancestry signal (PC1: rs = 0.138, P < 10−5; PC2: rs = 0.090, P = 0.002). This result suggests that, if separated along the major axes of differentiation between Europe and East Asia, individuals on the eastern end of the spectrum tend to be more similar to archaic human genomes. In contrast, after correction for multiple tests, we found no correlations between the archaic ancestry signal and intraregional PCs within Europe, and we did not find patterns of variation in archaic ancestry within Africa and America that could not be explained by more recent admixture with non-African populations (SI Results and Table S2).


Fig.1E: Interpolated spatial distribution of the frequency of Denisova alleles at SNPs where Denisova is different from chimpanzee and Neandertal. Sample localities are indicated with rectangles.

To disentangle the signal of Denisova admixture from the signal of Neanderthal admixture, we investigated the distribution of PC2, which separated Denisovans and Neandertals, and found that proximity to Neandertal increases with distance from Africa (individuals: rs = 0.078, P = 0.010). However, East Asians were an exception to this trend in that they were significantly closer to Denisovans compared with Europeans (P = 0.003), all West/Central Eurasians (P = 0.006), and Americans (P < 10−4). In a spatial interpolation of log-transformed PC2 values, the affinity to the Denisova genome seemed to be strongest in Southern China and Southeast Asia (Fig. 1D), which is noteworthy considering the supposed East Eurasian distribution of Denisovans (24). To investigate this geographical pattern using an alternative approach, we identified SNPs in chimpanzees and Neandertals that shared the ancestral allele, and Denisova had the derived allele; we computed the frequency of the derived Denisova allele in global modern human populations. Using the same method of spatial interpolation, we found that East Asian populations, particularly Southeast Asian populations, had, on average, a greater frequency of the derived Denisova allele compared with other populations (except for Oceanians) (Fig. 1E). For example, although the greatest Denisova allele frequency was found in Papuans (53.5%), Yizu from Southern China had a greater frequency of the Denisova allele than Melanesians from Bougainville (53.0% vs. 52.9%) (Table S3).

www.pnas.org/content/108/45/18301.full

About one percent of the genetic makeup of people from southern China and the surrounding region comes from an extinct group of humans dubbed the Denisovans, a new study says. Considered by some to be a sort of sister species to the Neanderthals, the Denisovans—who may have represented an entirely separate human species—are largely a mystery, though they're thought to have had big teeth. The latest find suggests that the two human types mated and bore offspring, and their descendants are still alive today in mainland Asia.

According to the "continuity with hybridization" theory, the hominins in Asia are descendants of H. erectus and they interbred with migrant groups from Africa and other parts of Eurasia. Many Western scientists think that Chinese nationalism is behind Chinese palaeontologists who support this hypothesis and they cannot accept the idea that H. sapiens evolved in Africa. It's quite possible that the Denisovans had a tiny proportion of H. erectus genes, which may be still part of some people's genetic makeup in Southeast Asia and China. The Denisovans contributed between 3 to 5 percent of their genetic material to the genomes of Melanesians.


Fig. 1. Modern human genetic variation projected on axes of variation defined by chimpanzee, Denisova, and Neandertal. (A) A model of hominin evolutionary history suggested in the work in ref. 24 with putative admixture events indicated by arrows. (B) Population means for each of 62 populations. (C) PC1 in individuals from Eurasia and America as a function of distance from East Africa (kilometers). (D) Interpolated spatial distribution of PC2 [transformed for visualization as (−1) × log10 (x + C), where x is the PC loading and C = 0.04231] in individuals from Eurasia, Oceania, and America. (E) Interpolated spatial distribution of the frequency of Denisova alleles at SNPs where Denisova is different from chimpanzee and Neandertal. Sample localities are indicated with rectangles.

To disentangle the signal of Denisova admixture from the
signal of Neanderthal admixture, we investigated the distribution
of PC2, which separated Denisovans and Neandertals, and found
that proximity to Neandertal increases with distance from Africa
(individuals: rs = 0.078, P = 0.010). However, East Asians were
an exception to this trend in that they were significantly closer to
Denisovans compared with Europeans (P = 0.003), all West/
Central Eurasians (P = 0.006), and Americans (P < 10−4).
In a spatial interpolation of log-transformed PC2 values, the affinity
to the Denisova genome seemed to be strongest in Southern
China and Southeast Asia (Fig. 1D), which is noteworthy considering
the supposed East Eurasian distribution of Denisovans
(24). To investigate this geographical pattern using an alternative
approach, we identified SNPs in chimpanzees and Neandertals
that shared the ancestral allele, and Denisova had the derived
allele; we computed the frequency of the derived Denisova allele
in global modern human populations. Using the same method
of spatial interpolation, we found that East Asian populations,
particularly Southeast Asian populations, had, on average,
a greater frequency of the derived Denisova allele compared
with other populations (except for Oceanians) (Fig. 1E). For
example, although the greatest Denisova allele frequency was
found in Papuans (53.5%), Yizu from Southern China had
a greater frequency of the Denisova allele than Melanesians
from Bougainville (53.0% vs. 52.9%) (Table S3).

Formal Test for Archaic Admixture. To test the hypothesis of Denisovan
ancestry in East Asians using an alternative approach, we
performed 4-population tests (23, 24, 40, 47, 48) on diploid genotype
data from different regions. Note that using population
allele frequencies is confounded by demographic effects (48) but
may also provide more power and a more diverse set of samples
compared with using low-coverage shotgun sequences from a
smaller set of individuals (23, 24). To investigate fine-scale geographical
patterns suggested by the PC analyses (Fig. 1 D and E),
we divided the East Asian populations in our dataset into two
groups, South and North of Beijing (with the North subgroup including
Beijing and Japan). We then tested the hypothesis of no
gene flow in the population topology (Denisova, chimpanzee),
(Northeast Asians, Southeast Asians) and found that allele frequencies
in the Southeastern Asian group were significantly more
similar to the Denisova data (D = 0.55 ± 0.23% SE, Z = 2.40)
(Table S4). In addition, we found that allele frequencies in the
Southeastern Asian group were significantly more similar to the
Denisova genome compared with the Neandertal genome (D =
0.66 ± 0.30%, Z = 2.22). This differentiation is not predicted by
the effects of ascertainment bias, which was observed in our simulations,
because ascertainment bias is expected to artificially increase
similarity to Neandertal under the model suggested by
previous studies (23, 24). Indeed, the only other pairwise regional
comparisons for which we see a strong pattern of similarity to
Denisova compared with both chimpanzee and Neandertal include
Oceanians (Fig. 3 and Table S4).


Fig. 2. PCA of archaic ancestry under a serial founder model with (or without) archaic admixture. 

An alternative explanation for the observed pattern would be
that the signal is caused by gene flow from the ancestors of
Oceanians (and/or East Asians) into the ancestors of the Denisovan
individual. Such gene flow would be expected to cause
a general affinity between Denisova and anatomically modern
human populations correlated with relatedness to the source
population of admixture. For example, if ancestors of the extant
Oceanian population contributed genetic material to the ancestry
of the Denisovan individual, it could be expected that Southeast
Asians would be genetically more similar to Denisova than other
human populations followed by Northeast Asians and Americans.
However, differences in the fraction of derived alleles
shared with Africans indicate that at least some of the gene flow
was into the ancestors of Oceanians (24). Moreover, the age
(>50,000 B.P.) and location (Altai, Siberia) of the Denisovan
individual (24) suggest that gene flow from the ancestors of extant
Oceanians into the descent of the Denisovan individual is a
less parsimonious hypothesis than a small fraction of Denisovan
related ancestry in extant East Asian populations, especially
because Denisova ancestry has been found in Oceania (24).
Although this Denisova ancestry in Southeast Asians could
possibly have been introduced by gene flow from indigenous
Oceanian populations after the introduction of Denisova-related
genetic variants in Oceanians, evidence for such large-scale migration
has not been found (56, 57). Moreover, this gene flow
would have had to be substantial enough not to dilute the
Denisova ancestry present in Oceanians beyond detection. Assuming
∼5% Denisova-related ancestry in Oceanians (24), any
fraction of Denisova-related ancestry in Southeast Asia would
require a ∼20 times as large contribution from Oceanian populations
to be explained solely by modern human gene flow.
Quantitative estimation of the precise fraction of Denisova-related
ancestry in Southeast Asian populations based on genotype
data are unfortunately sensitive to ascertainment bias and genetic
drift, and such estimates will require genome sequence data that
are currently unavailable. However, both the PCA results (Fig. 1B)
and the approximately six times lower absolute values of the D
statistic in tests between Northeast Asians and Southeast Asians
compared with tests between Northeast Asians and Oceanians
(Table S4) indicate a relatively low fraction of Denisova-related
ancestry. Thus, the fraction is likely to be smaller than both the
∼5% fraction of Denisova-related ancestry present in Oceanians
and the ∼2.5% fraction of Neandertal ancestry present in nonAfricans
(23, 24), perhaps around 1%.

The lack of evidence of Denisova ancestry in other Eurasian
populations indicates that this genetic material was introduced
into the ancestral population of Southeast Asians after the time
of divergence from Europeans, a date that has been estimated to
23–45 kya (58, 59) but could also have occurred considerably
earlier (27, 28, 30). The apparent absence of Denisova ancestry
in Native Americans in our study could be influenced by the
biased affinity to the Neandertal genome that is expected because
of ascertainment bias and genetic drift, but analyses of unascertained
low-coverage shotgun sequence data from a single Native
American individual resulted in a similar conclusion (24). If absent
in America, the Denisova component must have appeared in
the ancestors of East Asians after their divergence from Native
Americans, which has been dated to ∼14–30 kya (58, 60, 61).

Skoglund, Pontus, and Mattias Jakobsson. "Archaic human ancestry in East Asia." Proceedings of the National Academy of Sciences 108.45 (2011): 18301-18306.