Deepest Neandertal mtDNA split

The authors interpret the new result from HST as placing a lower boundary on an introgression from Africans to Neandertals at more than 290kya, which explains why Africans are genomically closer to Neandertals than to Denisovans.

Of course, when one looks at the mitochondrial phylogeny, it has the form:

(Denisovans, (Neandertals, Modern Humans))

Within the Modern Humans, Eurasians are a branch of a tree which is mostly African. This has been interpreted for decades as evidence for the Out of Africa hypothesis for the origin of Modern Humans. But, within the phylogeny as a whole, Modern Humans are a branch of the Eurasian tree. This has not (why?) in general been interpreted as evidence for Out of Eurasia for the common ancestor of Modern Humans and Neandertals.

It seems to me that this hypothesis, that Modern Humans and Neandertals stem from a non-African ancestor (a non-African population of H. heidelbergensis, for example), has much to recommend it.

Eurasia has twice the size of Africa and has been home to hominins for ~1.8 million years. It was inhabited by diverse hominins, and thanks to blind luck we discovered that as late as a few tens of thousands years ago, it also sported two of the populations that split off before anyone else: first H. floresiensis, and second Denisovans.

While a North African source of modern humans is plausible, the data seems to favor a Eurasian origin of the (Modern Human, Neandertal) ancestor.

Nature Communications 8, Article number: 16046 (2017) doi:10.1038/ncomms16046

Deeply divergent archaic mitochondrial genome provides lower time boundary for African gene flow into Neanderthals

Cosimo Posth, Christoph Wißing, Keiko Kitagawa, Luca Pagani, Laura van Holstein, Fernando Racimo, Kurt Wehrberger, Nicholas J. Conard, Claus Joachim Kind, Hervé Bocherens & Johannes Krause

Ancient DNA is revealing new insights into the genetic relationship between Pleistocene hominins and modern humans. Nuclear DNA indicated Neanderthals as a sister group of Denisovans after diverging from modern humans. However, the closer affinity of the Neanderthal mitochondrial DNA (mtDNA) to modern humans than Denisovans has recently been suggested as the result of gene flow from an African source into Neanderthals before 100,000 years ago. Here we report the complete mtDNA of an archaic femur from the Hohlenstein–Stadel (HST) cave in southwestern Germany. HST carries the deepest divergent mtDNA lineage that splits from other Neanderthals ∼270,000 years ago, providing a lower boundary for the time of the putative mtDNA introgression event. We demonstrate that a complete Neanderthal mtDNA replacement is feasible over this time interval even with minimal hominin introgression. The highly divergent HST branch is indicative of greater mtDNA diversity during the Middle Pleistocene than in later periods.

Link

Incipient Mongoloids (or elusive Denisovans) 105-125kya in China?

The authors claim that these archaic humans from China show parallels to both modern eastern Eurasians (Mongoloids) and to Neandertals. The relationship with the Neandertals makes them prime candidates for the elusive Denisovans who were a sister group to Neandertals but are morphologically unknown (since all we've got is a genome, teeth, and a pinky). The relationship with Mongoloids suggest an appearance of Mongoloid morphology pre-dating the transition to sapiens, and brings to mind past claims about incipient Caucasoid morphology in Neandertals. Did aspects of modern Eurasian morphology originate in pre-sapiens archaic Eurasians? Hopefully someone's studying DNA from these crania as we speak.

Science 03 Mar 2017: Vol. 355, Issue 6328, pp. 969-972 DOI: 10.1126/science.aal2482

Late Pleistocene archaic human crania from Xuchang, China 

Zhan-Yang Li et al.

Two early Late Pleistocene (~105,000- to 125,000-year-old) crania from Lingjing, Xuchang, China, exhibit a morphological mosaic with differences from and similarities to their western contemporaries. They share pan–Old World trends in encephalization and in supraorbital, neurocranial vault, and nuchal gracilization. They reflect eastern Eurasian ancestry in having low, sagittally flat, and inferiorly broad neurocrania. They share occipital (suprainiac and nuchal torus) and temporal labyrinthine (semicircular canal) morphology with the Neandertals. This morphological combination reflects Pleistocene human evolutionary patterns in general biology, as well as both regional continuity and interregional population dynamics.

Link

Denisovan ancestry in Oceanians (and some in South Asians)

Current Biology DOI: http://dx.doi.org/10.1016/j.cub.2016.03.037

The Combined Landscape of Denisovan and Neanderthal Ancestry in Present-Day Humans

Sriram Sankararaman et al.

Some present-day humans derive up to ∼5% [ 1 ] of their ancestry from archaic Denisovans, an even larger proportion than the ∼2% from Neanderthals [ 2 ]. We developed methods that can disambiguate the locations of segments of Denisovan and Neanderthal ancestry in present-day humans and applied them to 257 high-coverage genomes from 120 diverse populations, among which were 20 individual Oceanians with high Denisovan ancestry [ 3 ]. In Oceanians, the average size of Denisovan fragments is larger than Neanderthal fragments, implying a more recent average date of Denisovan admixture in the history of these populations (p = 0.00004). We document more Denisovan ancestry in South Asia than is expected based on existing models of history, reflecting a previously undocumented mixture related to archaic humans (p = 0.0013). Denisovan ancestry, just like Neanderthal ancestry, has been deleterious on a modern human genetic background, as reflected by its depletion near genes. Finally, the reduction of both archaic ancestries is especially pronounced on chromosome X and near genes more highly expressed in testes than other tissues (p = 1.2 × 10−7 to 3.2 × 10−7 for Denisovan and 2.2 × 10−3 to 2.9 × 10−3 for Neanderthal ancestry even after controlling for differences in level of selective constraint across gene classes). This suggests that reduced male fertility may be a general feature of mixtures of human populations diverged by >500,000 years.

Link

Neandertal and Denisovan DNA from Melanesians

Admixture models are out of control these days, with 4 inferred archaic introgressions into three groups of Eurasians (Europeans, East Asians, Melanesians). The model on the left has to be a simplification/incomplete/wrong in some way (Melanesians are not an outgroup to Europeans and East Asians; Europeans have "Basal Eurasian" ancestry via Early European Farmers; Denisovans have some kind of weird archaic ancestry that Neandertals don't, and according to a recent study, the Altai Neandertal also has some kind of weird Proto-Modern Human lineage). In any case, this may not matter much for the problem at hand which is excavating archaic DNA from Melanesian genomes.

But, if you combined all the admixtures inferred in the literature, you'd probably need something like 8 admixtures to  model 5 populations. Time and data will show which of them are real, and reveal news ones (e.g., in Africans, who remain blissfully simple in the absence of archaic African genomes).

Science DOI: 10.1126/science.aad9416

Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals

Benjamin Vernot et al.

Although Neandertal sequences that persist in the genomes of modern humans have been identified in Eurasians, comparable studies in people whose ancestors hybridized with both Neandertals and Denisovans are lacking. We developed an approach to identify DNA inherited from multiple archaic hominin ancestors and applied it to whole-genome sequences from 1523 geographically diverse individuals, including 35 new Island Melanesian genomes. In aggregate, we recovered 1.34 Gb and 303 Mb of the Neandertal and Denisovan genome, respectively. We leverage these maps of archaic sequence to show that Neandertal admixture occurred multiple times in different non-African populations, characterize genomic regions that are significantly depleted of archaic sequence, and identify signatures of adaptive introgression.

Link

Sima de los Huesos hominins were Proto-Neandertals

Nature (2016) doi:10.1038/nature17405

Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins

Matthias Meyer, Juan-Luis Arsuaga, Cesare de Filippo, Sarah Nagel, Ayinuer Aximu-Petri, Birgit Nickel, Ignacio Martínez, Ana Gracia, José María Bermúdez de Castro, Eudald Carbonell, Bence Viola, Janet Kelso, Kay Prüfer & Svante Pääbo

A unique assemblage of 28 hominin individuals, found in Sima de los Huesos in the Sierra de Atapuerca in Spain, has recently been dated to approximately 430,000 years ago1. An interesting question is how these Middle Pleistocene hominins were related to those who lived in the Late Pleistocene epoch, in particular to Neanderthals in western Eurasia and to Denisovans, a sister group of Neanderthals so far known only from southern Siberia. While the Sima de los Huesos hominins share some derived morphological features with Neanderthals, the mitochondrial genome retrieved from one individual from Sima de los Huesos is more closely related to the mitochondrial DNA of Denisovans than to that of Neanderthals2. However, since the mitochondrial DNA does not reveal the full picture of relationships among populations, we have investigated DNA preservation in several individuals found at Sima de los Huesos. Here we recover nuclear DNA sequences from two specimens, which show that the Sima de los Huesos hominins were related to Neanderthals rather than to Denisovans, indicating that the population divergence between Neanderthals and Denisovans predates 430,000 years ago. A mitochondrial DNA recovered from one of the specimens shares the previously described relationship to Denisovan mitochondrial DNAs, suggesting, among other possibilities, that the mitochondrial DNA gene pool of Neanderthals turned over later in their history.

Link

Are living Africans nested within Eurasian genetic variation (?)

The picture on the left (source) shows quite nicely that according to current understanding, Africans are nested within Eurasian genetic variation. The modern humans have the following structure:

(Early modern human lineage detected as admixture in the Altai Neandertal, ((Asians, Europeans), Africans)),

and then there are two deeper layers of Eurasian hominins (Neandertal/Denisovans) and the "Mystery hominin" that mixed into Denisovans.

Africans are thus just a leaf of the Eurasian family tree, casting serious doubt -if this model is to be believed- to the position that H. sapiens originated in Africa and are descended from people who never left the continent. It seems much simpler to derive them from an early migration (~200kya?) from Asia which would nicely explain why the continent's first sapiens populations appear tentatively in the northeastern corner, and why they do not replace archaic hominins for most of the 200 thousand years until today. In a reversal of perspective it is not Skhul/Qafzeh that are the "migration that failed", but rather the Omo 1 outlier is.

One might argue that this is just a consequence of the fact that lots of ancient genomes have been published from Eurasia, but none from Africa. So, there are all these branches of deep archaic Eurasians simply because there are no genomes of deep archaic Africans.

But, this explanation does not really work. If Africans had any significant ancestry deeper than the split of "Early modern human lineage", then this lineage would be closer to (Asians, Europeans) than to Africans. However, Kulhwilm et al. assert that it is "equally related to present-day Africans and non-Africans". If they had any ancestry deeper than ((Denisovans, Neandertals), H. sapiens), then (Denisovans, Neandertals) would be closer to non-Africans than to Africans. Well, they are, but this is now satisfactorily explained by admixture from (Denisovans, Neandertals) into non-Africans, thanks to genomes like Ust Ishim, K14, and Oase which have big chunks of Neandertal ancestry that can't be explained any other way. No need to invoke any such lineage when a simpler well-documented alternative exists.

The presented phylogeny negates the possibility of the existence of collateral archaic African kin of the extant Africans that admixed with them, and leads to the conclusion that Africans are nested within Eurasian variation because they really are. This is, of course, incompatible with the statistically inferred archaic introgression into Africans which indeed postulates the existence of such archaic Africans and their contribution to extant ones.

I don't see any obvious flaw with Kulhwilm et al. but if its model is right, then it does lead to some rather extreme conclusions. It contradicts the evidence for archaic introgression; if Hsieh et al. is wrong (and I don't seen any evidence for that either), then Kulhwilm et al. can be saved, but only if Africans are really nested within several layers of Eurasian variation and did not admix at all with the morphologically diverse archaic Africans of the paleoanthropological record. This also doesn't seem right now that we know that sapiens-archaic admixture was a common occurrence in Eurasia. The reversal of perspective alluded to above may help here by removing the opportunity for admixture, but that too is, of course, an extraordinary claim.

In sum, I am rather convinced that the latest discoveries have muddled the origin story of our species and some major rethink is needed to evaluate the totality of the evidence.

Two more Denisovans (Sawyer, Renaud et al. 2015)

PNAS doi: 10.1073/pnas.1519905112

Nuclear and mitochondrial DNA sequences from two Denisovan individuals

Susanna Sawyer, Gabriel Renaud et al.

Denisovans, a sister group of Neandertals, have been described on the basis of a nuclear genome sequence from a finger phalanx (Denisova 3) found in Denisova Cave in the Altai Mountains. The only other Denisovan specimen described to date is a molar (Denisova 4) found at the same site. This tooth carries a mtDNA sequence similar to that of Denisova 3. Here we present nuclear DNA sequences from Denisova 4 and a morphological description, as well as mitochondrial and nuclear DNA sequence data, from another molar (Denisova 8) found in Denisova Cave in 2010. This new molar is similar to Denisova 4 in being very large and lacking traits typical of Neandertals and modern humans. Nuclear DNA sequences from the two molars form a clade with Denisova 3. The mtDNA of Denisova 8 is more diverged and has accumulated fewer substitutions than the mtDNAs of the other two specimens, suggesting Denisovans were present in the region over an extended period. The nuclear DNA sequence diversity among the three Denisovans is comparable to that among six Neandertals, but lower than that among present-day humans.

Link

In search of the source of Denisovan ancestry

bioRxiv http://dx.doi.org/10.1101/017475

Denisovan Ancestry in East Eurasian and Native American Populations.

Pengfei Qin , Mark Stoneking

Although initial studies suggested that Denisovan ancestry was found only in modern human populations from island Southeast Asia and Oceania, more recent studies have suggested that Denisovan ancestry may be more widespread. However, the geographic extent of Denisovan ancestry has not been determined, and moreover the relationship between the Denisovan ancestry in Oceania and that elsewhere has not been studied. Here we analyze genome-wide SNP data from 2493 individuals from 221 worldwide populations, and show that there is a widespread signal of a very low level of Denisovan ancestry across Eastern Eurasian and Native American (EE/NA) populations. We also verify a higher level of Denisovan ancestry in Oceania than that in EE/NA; the Denisovan ancestry in Oceania is correlated with the amount of New Guinea ancestry, but not the amount of Australian ancestry, indicating that recent gene flow from New Guinea likely accounts for signals of Denisovan ancestry across Oceania. However, Denisovan ancestry in EE/NA populations is equally correlated with their New Guinea or their Australian ancestry, suggesting a common source for the Denisovan ancestry in EE/NA and Oceanian populations. Our results suggest that Denisovan ancestry in EE/NA is derived either from common ancestry with, or gene flow from, the common ancestor of New Guineans and Australians, indicating a more complex history involving East Eurasians and Oceanians than previously suspected.

Link

Bias in estimators of archaic admixture

arXiv:1412.6691 [q-bio.PE]

Bias in Estimators of Archaic Admixture

Alan R. Rogers, Ryan J. Bohlender

(Submitted on 20 Dec 2014)

This article evaluates bias in one class of methods used to estimate archaic admixture in modern humans. These methods study the pattern of allele sharing among modern and archaic genomes. They are sensitive to "ghost" admixture, which occurs when a population receives archaic DNA from sources not acknowledged by the statistical model. The effect of ghost admixture depends on two factors: branch-length bias and population-size bias. Branch-length bias occurs because a given amount of admixture has a larger effect if the two populations have been separated for a long time. Population-size bias occurs because differences in population size distort branch lengths in the gene genealogy. In the absence of ghost admixture, these effects are small. They become important, however, in the presence of ghost admixture. Estimators differ in the pattern of response. Increasing a given parameter may inflate one estimator but deflate another. For this reason, comparisons among estimators are informative. Using such comparisons, this article supports previous findings that the archaic population was small and that Europeans received little gene flow from archaic populations other than Neanderthals. It also identifies an inconsistency in estimates of archaic admixture into Melanesia.

Link

Altitude adaptation in Tibetans came from Denisovans

This is somewhat strange given that Denisova cave is not at high altitude.

Nature (2014) doi:10.1038/nature13408

Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA

Emilia Huerta-Sánchez et al.

As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau1, 2, 3. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans4, 5, 6, 7, 8, 9, 10, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.

Link

Archaic admixture in Eurasians with hominins that diverged 0.9 and 3.5 million years ago?

One of the interesting stories of the Neandertal Genome Project is how earlier evidence of archaic introgression into Eurasians was later confirmed when the Neandertal genome was published. It is always trickier to make a case for archaic introgression in the absence of an actual archaic genome, so I expect this paper to be subjected to a high level of scrutiny. In any case, I'm glad that it's on the arXiv so that the scrutiny process can begin by anyone who cares about the subject.

arXiv:1404.7766 [q-bio.PE]

Genome-wide Scan of Archaic Hominin Introgressions in Eurasians Reveals Complex Admixture History

Ya Hu, Yi Wang, Qiliang Ding, Yungang He, Minxian Wang, Jiucun Wang, Shuhua Xu, Li Jin

Introgressions from Neanderthals and Denisovans were detected in modern humans. Introgressions from other archaic hominins were also implicated, however, identification of which poses a great technical challenge. Here, we introduced an approach in identifying introgressions from all possible archaic hominins in Eurasian genomes, without referring to archaic hominin sequences. We focused on mutations emerged in archaic hominins after their divergence from modern humans (denoted as archaic-specific mutations), and identified introgressive segments which showed significant enrichment of archaic-specific mutations over the rest of the genome. Furthermore, boundaries of introgressions were identified using a dynamic programming approach to partition whole genome into segments which contained different levels of archaic-specific mutations. We found that detected introgressions shared more archaic-specific mutations with Altai Neanderthal than they shared with Denisovan, and 60.3% of archaic hominin introgressions were from Neanderthals. Furthermore, we detected more introgressions from two unknown archaic hominins whom diverged with modern humans approximately 859 and 3,464 thousand years ago. The latter unknown archaic hominin contributed to the genomes of the common ancestors of modern humans and Neanderthals. In total, archaic hominin introgressions comprised 2.4% of Eurasian genomes. Above results suggested a complex admixture history among hominins. The proposed approach could also facilitate admixture research across species.

Link

IBD sharing between modern humans, Denisovans and Neandertals

bioRxiv doi:doi: 10.1101/003988

Sharing of Very Short IBD Segments between Humans, Neandertals, and Denisovans

Gundula Povysil, Sepp Hochreiter

We analyze the sharing of very short identity by descent (IBD) segments between humans, Neandertals, and Denisovans to gain new insights into their demographic history. Short IBD segments convey information about events far back in time because the shorter IBD segments are, the older they are assumed to be. The identification of short IBD segments becomes possible through next generation sequencing (NGS), which offers high variant density and reports variants of all frequencies. However, only recently HapFABIA has been proposed as the first method for detecting very short IBD segments in NGS data. HapFABIA utilizes rare variants to identify IBD segments with a low false discovery rate. We applied HapFABIA to the 1000 Genomes Project whole genome sequencing data to identify IBD segments which are shared within and between populations. Some IBD segments are shared with the reconstructed ancestral genome of humans and other primates. These segments are tagged by rare variants, consequently some rare variants have to be very old. Other IBD segments are also old since they are shared with Neandertals or Denisovans, which explains their shorter lengths compared to segments that are not shared with these ancient genomes. The Denisova genome most prominently matched IBD segments that are shared by Asians. Many of these segments were found exclusively in Asians and they are longer than segments shared between other continental populations and the Denisova genome. Therefore, we could confirm an introgression from Deniosvans into ancestors of Asians after their migration out of Africa. While Neandertal-matching IBD segments are most often shared by Asians, Europeans share a considerably higher percentage of IBD segments with Neandertals compared to other populations, too. Again, many of these Neandertal-matching IBD segments are found exclusively in Asians, whereas Neandertal-matching IBD segments that are shared by Europeans are often found in other populations, too. Neandertal-matching IBD segments that are shared by Asians or Europeans are longer than those observed in Africans. This hints at a gene flow from Neandertals into ancestors of Asians and Europeans after they left Africa. Interestingly, many Neandertal- or Denisova-matching IBD segments are predominantly observed in Africans - some of them even exclusively. IBD segments shared between Africans and Neandertals or Denisovans are strikingly short, therefore we assume that they are very old. This may indicate that these segments stem from ancestors of humans, Neandertals, and Denisovans and have survived in Africans.

Link

A Neandertal from the Altai Mountains (Prüfer et al. 2013)

There seems to have been a lot of inter-"species" sex during the Paleolithic (left), and that's just from a handful of Eurasian hominins sequenced so far.

Who knows what other Middle Paleolithic genomes might be in the works? My guess is that once all is said and done, the tree of Homo will fill up with "red" admixture edges, and those who argued for a single Homo lineage evolving over hundreds of thousands of years, with gene flow between regional populations, will have the upper hand.

An interesting finding is that the introgressing Neandertal (N.I.) was related to the Mezmaiskaya sample from the Caucasus rather than to the Vindija sample from Croatia or the new Altai Neandertal. It'd be great to have the genome of a bona fide "progressive" Near Eastern Neandertal.

UPDATE I (Dec. 19):

Reading the 249 pages of supplementary information is likely to reveal a lot of gems of new information.In SI 13 we see that:

We detect likely West Eurasian gene flow into the ancestors of Yoruba West Africans within the last ten thousand years, which indirectly contributed a small amount of Neandertal ancestry to Yoruba.

and:

These results mean that we have not identified any sub-Saharan African sample that we are confident has no evidence of back-to-Africa migration. Our best candidate at present is the Dinka but it is possible that with a phased genome or large sample sizes we would detect evidence of non-African ancestry in this population as well.

Nature (2013) doi:10.1038/nature12886

The complete genome sequence of a Neanderthal from the Altai Mountains

Kay Prüfer et al.

We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.

Link

400 thousand year old human mtDNA from Sima de los Huesos

It will come to no surprise to people who noticed an earlier paper on cave bear mtDNA from Atapuerca that the folks at the Max Planck Institute would try to do the same for the plentiful human remains found in the Pit of Bones.

A new paper in Nature reports their success, and overnight increases by an order of magnitude the time depth for which we now have human mtDNA from what is commonly designated as Homo heidelbergensis, from right in the middle of the Middle Pleistocene. Obviously, this opens new vistas for archaeogenetic research, making it possible to directly look at early pre-sapiens forms of humans, and not only on their final forms prior to their replacement, the Neandertals and Denisovans.

The most impressive aspect of the new paper is most likely the technical challenges that the researchers must've overcome to achieve this result. The cave bear DNA showed that this was possible, but human DNA adds an additional complication in the form of contamination by a closely related species, us.

But, the new evolutionary result which will interest those of us not interested in the minutiae of biomolecules will no doubt be the fact that the Sima hominin's mtDNA formed a clade with the much more recent Denisova girl.

Until now, we knew that Neandertal mtDNA grouped together and so did modern human mtDNA. The two groups shared a Middle Pleistocene common ancestor and a much more distant common ancestor (~1 million years) with the mtDNA found in Denisova. The new Sima specimen shares descent from Denisova. This is important because it shows that whatever archaic human population the Denisovan mtDNA belonged to also extended to western Europe. And, surprisingly, the Sima specimen did not group with Neandertals, as might be expected because of the incipient Neanderthaloid morphology of the Sima hominins which has been a matter of controversy as it pushes back the evolutionary lineage of H. neandertalensis deeper into the Middle Pleistocene that some researchers accept.

Before this paper, it was believed that H. heidelbergensis evolved somewhere (perhaps Near East or Africa), a subset of it evolved to H. sapiens in Africa, and a different subset evolved in Eurasia, leading up to H. neandertalensis in the west, and unknown forms in the east, of which the Denisova girl was a matrilineal descendant. The next question is: when did Neandertals and Neandertal mtDNA appear in Europe? 

It can now be hoped that such questions will be answered directly. The Sima individual studied in this paper is not some frozen specimen from the Arctic, preserved by a freak accident in pristine form for hundreds of thousands of years, but a person who lived in Southwestern Europe. I am fairly sure that this won't be the last really old human we see a paper about in the coming years. Human mtDNA used to present a simple picture at the time of the discovery of African mitochondrial Eve: the deepest splits were in Africa and Eurasians belonged to a subset of African variation. But, as more and more archaic Eurasian mtDNA is sampled, it now appears that modern human mtDNA is a subset of world human mtDNA whose deepest splits are in Eurasia, and the next deepest splits are in Africa. Obviously, this may be a consequence of the fact that archaic human mtDNA has only been sampled from Eurasia, for factors relating to DNA preservation. But, it is nonetheless interesting to wonder where on the tree the mtDNA of archaic Africans would fall.

Nature (2013) doi:10.1038/nature12788

A mitochondrial genome sequence of a hominin from Sima de los Huesos

Matthias Meyer et al.

Excavations of a complex of caves in the Sierra de Atapuerca in northern Spain have unearthed hominin fossils that range in age from the early Pleistocene to the Holocene1. One of these sites, the ‘Sima de los Huesos’ (‘pit of bones’), has yielded the world’s largest assemblage of Middle Pleistocene hominin fossils2, 3, consisting of at least 28 individuals4 dated to over 300,000 years ago5. The skeletal remains share a number of morphological features with fossils classified as Homo heidelbergensis and also display distinct Neanderthal-derived traits6, 7, 8. Here we determine an almost complete mitochondrial genome sequence of a hominin from Sima de los Huesos and show that it is closely related to the lineage leading to mitochondrial genomes of Denisovans9, 10, an eastern Eurasian sister group to Neanderthals. Our results pave the way for DNA research on hominins from the Middle Pleistocene.

Link

ESHE 2013 abstracts

219 pages worth of abstracts from the upcoming meeting of the European Society for the study of Human Evolution (pdf).

I will post some excerpts:

Evolutionary History And Biological Diversity Of Homo Sapiens In Southeast Asia: Contour Shape Analysis Of Modern Human Upper Molars:

The evolutionary history and the pattern of biological diversity of modern humans in Southeast Asia has long been regarded as resulting of two major migrations waves. In this hypothesis it is generally considered that a first wave of migration (generally referred as “Australo-Melanesians”) reached Australia around 60000 BP while the second wave (often referred as “Mongoloids”) is correlated to a demic diffusion of the Neolithic from a Southeast China homeland which started around mid-Holocene. ... Our results also bring very interesting perspectives concerning the detection of the signature of a possible Denisovan admixture in the phenotype of modern human populations. Indeed, past and recent modern human groups which are hypothetically sharing Denisovan ancestry have closer phenetic affinities with each other than with other populations.

Podium Presentation: Session 9, Sa (14:20) A fine scale survey of the worldwide similarity between humans and archaic hominids and its implication on the proposed admixture scenario 

Since the publications of Green et al. 2010 and Reich et al. 2010, several investigations have followed suit addressing the question regarding anatomically modern human and archaic hominin admixture. The genetic analyses of the Neanderthal draft genome and the Denisova genome concluded that these archaic hominins made a 1-4% contribution to non-African populations and 4-6% contribution to Melanesian populations, respectively. The argument of whether the observed genetic similarity is consistent with admixture or ancient substructure is still under debate. While observations have been consistent with an admixture scenario of Neanderthals and the ancestors of non-Africans coming into contact 50 – 80 kya in the Middle East, the lack of power in these experiments falter in providing reliable results. Here we look at the relationship between AMH and these archaic hominins on a fine-scale level by using several methods (including revised D-statistic) on the Neanderthal draft genome, Denisova high-coverage genome, and a collection of published and unpublished genotype and sequence data. We use our findings to clarify the proposed admixture scenario as well as discuss new findings in newly analyzed comparisons of African, South Asian and American populations with archaic hominins, Neanderthal and Denisova. Our results shed light on understanding the observed genetic similarity within and between humans (African and non-African) and archaic hominins, particularly in relevance to the admixture versus ancient substructure scenarios. 

How ‘modern’ are the earliest Homo sapiens? 

Previous research (reviewed in Trinkaus, 2005) has suggested that the African and western Asian contemporaries of Neandertals, generally considered to be the earliest Homo sapiens, are not particularly ‘modern’ looking in their cranial anatomy. Here we test whether the dental morphological ‘signal’ agrees with this assessment. We examined and recorded dental morphological variation in the earliest H. sapiens and asked: how ‘modern’ are they dentally? We used a Bayesian statistical approach to classifying individuals into two possible groups based on dental non-metric traits. e classification was based on dental trait frequencies and sample sizes for two ’known’ samples of 120 Neandertals and 106 Upper Paleolithic H. sapiens individuals. A cross- validation test of these individuals resulted in a correct classification rate of 95%, which is even better than the results of a previous study using the same method based on fewer individuals (Bailey et al 2009). Our early H. sapiens sample included 41 individuals from Southern Africa (Die Kelders, Klasies River Mouth and Equus Cave), Northern Africa (Temara, El Harhoura, Dar es Soltan) and the Levant (Qafzeh, Skhul). We treated our early H. sapiens individuals as ‘unknown’ and calculated the probability that each belonged to either the Upper Paleolithic or Neandertal sample. While understanding that technically these individuals did not belong to either group, we hypothesized that if the earliest H. sapiens were already dentally modern then, when forced into a group, they should fall into the Upper Paleolithic H. sapiens group. We also hypothesized that if there had been significant admixture in the Levant during the initial dispersal out of Africa - as has been sometimes proposed based on paleontological - and more recently on genetic - evidence (Green et al 2010) that these samples would have the largest proportion of individuals classified as Neandertal. Our results indicated that this was not the case. While a surprising number (27%) of early H. sapiens did classify as Neandertal, the smallest proportion of these came from the Levant (7% - one out of 14 individuals). The African sample was more of a ‘mixed bag’. None of the individuals from Die Kelders or Klaises River Mouth classified as Neandertal, while four out of five of the individuals from Equus Cave did. Moreover, 6 out of 13 (46%) of the Northern African individuals were classified as Neandertal. An inspection of the individual specimens that classified as Neandertals revealed that in most cases it is the predominance of primitive features, rather than derived Neandertal traits, that is driving the classification. We conclude (1) by the time the earliest H. sapiens dispersed from Africa they had already attained a more-or-less ‘modern’ dental pattern; (2) in the past, as is the case today, Late Pleistocene Africans were not a homogeneous group, some retained primitive dental traits in higher proportions than others. Furthermore, we acknowledge that while our method is an excellent tool for discriminating between Upper Paleolithic H. sapiens and Neandertals, it may not be appropriate for testing Neandertal – H. sapiens admixture because all traits (primitive and derived) are weighed equally. 

The potential for catastrophic impact of the Campanian Ignimbrite (CI) tephra on human evolution: new data from the Lower Danube loess steppe:

Here we investigate an unexpectedly thick CI tephra deposit at Urluia in the southeast Romanian loess steppe, 1200 km from the super-eruption vent in Italy. Existing models suggest that the CI tephra thickness might reach a maximum 5-10 cm in Eastern Europe; the Urluia ash deposit is up to 100 cm thick. Additional, recently discovered Lower Danube sites also reveal substantially thicker than modelled CI ash beds. 

Radiocarbon dating the extinction of European Neanderthals

The transitional industries and their makers:

The demonstration of modern settlements pre-dating the earliest Aurignacian in Europe has important implications (Hublin 2012). It is consistent with a patchy pattern of modern colonization, with some significant chronological overlap between Neandertals and modern humans on a continental scale. In this model innovations observed in the Neandertal world around or after 50 ka cal BP may have resulted from cultural diffusion triggered by these influxes of populations into western Eurasia.

The Upper Paleolithic of the Ikh Tulberin Gol (Northern Mongolia): new excavations at the Tolbor 16 open-air site:

Numerous questions remain regarding the timing and the context of Upper Paleolithic emergence in Northeast Asia. Available data allow the recognition of a form of Initial Upper Paleolithic (IUP) (Brantingham et al, 2001) documented in the Altai circa 45-40 ka uncal BP (Goebel et al., 1993, Derevianko et al, 2000, Zwyns et al., 2012), in the Cis- and Transbaikal around 40 ka uncal BP (Lbova, 2008) ...

New data on the radiocarbon chronology of the Stretleskayan at Kostenki (Voronezh, Central Russia) :

It concerns cultural layer III at Kostenki 12 and cultural layer V at Kostenki I, respectively previously dated 36,280±360 and 34,900 ±350 BP in Groningen (Damblon et al., 1996). ... Remaining material of the charcoal sample from cultural layer III at Kostenki 12, previously dated 36,280 ±250 BP, was also submitted for dating to Oxford with ABOx-SC pretreatment. the results show that the two Groningen dates and the three Oxford dates are in good agreement and fit within a time interval of 1 millennium, but provide ages several millennia older than the ages obtained previously. Taking into account this new chronology, the appearance of the Stretleskayan at Kostenki will be compared with the chronological background of the Early Aurignacian, Szeletian and Bohunician occurrences in the MiddleDanube sequence, also based on ABA and ABOx-SC cross-dating (Haesaerts et al., 2013). 

Two Waves of Paleolithic Settlers Migrations to North West Beringia in Pleistocene End (End of Karginsky Interstadial) :

Way of 1st wave is marked by sites Afontova Gora V, Ust-Kova on Angara, than along Lena river up to Central Ykut plain, turn Aldan (Ikhine I etc), than round Kolyma plain to Chukotka, where they left abt 30 Ka Orlovka II site in North of West and Kymyneykey site in North of East Chukotka. In Aldan basin migration slowly down. Its reason could be glaciation of Verkhoyansk and Chersky ranges. During this delay “technical re-equipment” happened of migrations. Orlovka II and Kymyney artefacts are clear Aldan. 2nd wave migration was abt 29-28 Ka during final karginsky (middle: würm, wisconsin) warming, when paleoclimate along all northern outskirts of Asia was like to recent or more warm (Drozdov and Laukhin, 2010). Migrants of 2nd wave went to Yana mouth and left here site. Artifacts of this site don’t have Aldanian traditions, but are very close to Yeniseisk. There were little of favorable niches to North of South Mountain Belt; and their demographic capacity were nor big. 

Modern human dispersal into Eurasia: Preliminary results of the multi-disciplinary project on the replacement of Neanderthals by modern humans (RNMH)

Both the chronometric dating and the geographic distribution of archaeological entities indicate that modern human populations equipped themselves with blade products based on the Levallois method, a technology that emerged in North Africa (Taramsan) around 60 ka and then dispersed into the Eastern Mediterranean Levant (Emiran) between 49 and 48 ka. Blade technology further expanded into Eastern and Central Europe (Bachokirian and Bohunician) between 48 and 45 ka and into Southern Siberia (Kara-Bom horizons 6 and 5) at around 47 ka. The rapid expansion of modern humans into Western and Eastern Eurasia followed by the demise of archaic populations in these regions may imply technological and cognitive advantages of modern humans. 

ASHG 2013 abstracts

Feel free to point me to more interesting abstracts than the ones I noticed during my "first pass".

Morphometric and ancient DNA study of human skeletal remanants in Indian Subcontinent.
N. Rai et al.

Recovery and sequencing of mtDNA from ancient human remnants is a daunting task but provides valuable information about human migrations and evolution. Our present study is the first to recover, amplify and sequence (HVR and coding regions of mtDNA) inadequately preserved and highly degraded (1.5 Ky to ≤1.0 Ky ago) hominids mitochondrial DNA of three most intriguing and indigenous ancient population of South and South-East Asia (Myanmar=20 Buried individuals, Nicobar Islands=15 and Andaman Island=6). Following all parameters and to avoid the chance of contamination we independently extracted and sequenced the DNA in two different labs and measured the cranial variability in all hominid skulls using 128 cranial landmarks, compiled 3D morphometrics, genetic data of ancient DNA samples and analyzed the admixture and genetic affinities of above three populations. Results showed the predominant frequency of F1a1 and complete absence of 9bp deletion in ancient Nicobarese. Unlike in previous reports on modern Nicobarese, the high frequency of F1a1 haplogroup in ancient Nicobarese show the probable migration of Nicobarese from South East Asia and the complete absence of 9bp deletion suggests the different events of settlement. This study failed to detect genetic affinities of Burmese with Nicolbarese even though their phenotype and language appears to be same. We first time report any kind of population study on Burmese populations and with the genetic affinity of Burmese with East Asian, East Indian (Including Gadhwal region of Himalaya) and Bangladeshi populations, we found significant admixture with West Eurasians. Our study strongly supports the West Eurasian and East Asian route of migration and settlement of early Burmese population. The three populations in the present study are quite different in their genetic structure but 3D morphometric study using huge number of landmarks explains a close homology among these populations and this can be explained by the role of climatic signature on these populations.

 Y chromosomes of ancient Hunnu people and its implication on the phylogeny of East Asian linguistic families. 
LL. Kang et al.

The Hunnu (Xiongnu) people, also called Huns in Europe, were the largest ethnic group to the north of Han Chinese until the 5th century. The ethno-linguistic affiliation of the Hunnu is controversial among Yeniseian, Altaic, Uralic, and Indo-European. Ancient DNA analyses on the remains of the Hunnu people had shown some clues to this problem. Y chromosome haplogroups of Hunnu remains included Q-M242, N-Tat, C-M130, and R1a1. Recently, we analyzed three samples of Hunnu from Barköl, Xinjiang, China, and determined Q-M3 haplogroup. Therefore, most Y chromosomes of the Hunnu samples examined by multiple studies are belonging to the Q haplogroup. Q-M3 is mostly found in Yeniseian and American Indian peoples, suggesting that Hunnu should be in the Yeniseian family. The Y chromosome diversity is well associated with linguistic families in East Asia. According to the similarity in the Y chromosome profiles, there are four pairs of congenetic families, i.e., Austronesian and Tai-Kadai, Mon-Khmer and Hmong-Mien, Sino-Tibetan and Uralic, Yeniseian and Palaesiberian. Between 4,000-2,000 years before present, Tai-Kadai, Hmong-Mien, Sino-Tibetan, and Yeniseian languages transformed into toned analytic languages, becoming quite different from the rest four. Since Hunnu was in the Yeniseian family, all these four toned families were distributed in the inland of China during the transformations. There must be some social or biological factors induced the transformations at that time, which is worth doing more linguistic and genetic researches.

Genomic scans for haplotypes of Denisova and Neanderthal ancestry in modern human populations.
F. L. Mendez, M. F. Hammer University of Arizona, Tucson, AZ., USA.

Evidence of archaic introgression into modern humans has accumulated in recent years. While most efforts to characterize the introgression process have relied on genome averages, only a small number of introgressive haplotypes have been shown to have an archaic origin after rejection of the alternative hypothesis of incomplete lineage sorting. Accurate identification of introgressive haplotypes is crucial both to characterize potentially functional consequences of archaic admixture and to quantify more precisely the genomic impact of archaic introgression. We perform two independent genomic scans for haplotypes of Denisova and of Neanderthal origin in a geographically diverse sample of complete genome sequences. These scans are based on the local sharing of polymorphisms and linkage disequilibrium, respectively. The analysis of concordance between the methods is then used to estimate the power and to compare demographic inference when performed using either all the data or just the genomic regions with no evidence of introgression. Moreover, we evaluate the extent to which Denisova haplotypes are observed in non-Melanesian populations, and investigate whether the presence of such haplotypes is better explained by their persistence in the population since introgression or by more recent gene flow from Melanesians.

Admixture Estimation in a Founder Population. 

Y. Banda1 et al.

Admixture between previously diverged populations yields patterns of genetic variation that can aid in understanding migrations and natural selection. An understanding of individual admixture (IA) is also important when conducting association studies in admixed populations. However, genetic drift, in combination with shallow allele frequency differences between ancestral populations, can make admixture estimation by the usual methods challenging. We have, therefore, developed a simple but robust method for ancestry estimation using a linear model to estimate allele frequencies in the admixed individual or sample as a function of ancestral allele frequencies. The model works well because it allows for random fluctuation in the observed allele frequencies from the expected frequencies based on the admixture estimation. We present results involving 3,366 Ashkenazi Jews (AJ) who are part of the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort and genotyped at 674,000 SNPs, and compare them to the results of identical analyses for 2,768 GERA African Americans (AA). For the analysis of the AJ, we included surrogate Middle Eastern, Italian, French, Russian, and Caucasus subgroups to represent the ancestral populations. For the African Americans, we used surrogate Africans and Northern Europeans as ancestors. For the AJ, we estimated mean ancestral proportions of 0.380, 0.305, 0.113, 0.041 and 0.148 for Middle Eastern, Italian, French, Russian and Caucasus ancestry, respectively. For the African Americans, we obtained estimated means of 0.745 and 0.248 for African and European ancestry, respectively. We also noted considerably less variation in the individual admixture proportions for the AJ (s.d. = .02 to .05) compared to the AA (s.d.= .15), consistent with an older age of admixture for the former. From the linear model regression analysis on the entire population, we also obtain estimates of goodness of fit by r2. For the analysis of AJ, the r2 was 0.977; for the analysis of the AA, the r2 was 0.994, suggesting that genetic drift has played a more prominent role in determining the AJ allele frequencies. This was confirmed by examination of the distribution of differences for the observed versus predicted allele frequencies. As compared to the African Americans, the AJ differences were significantly larger, and presented some outliers which may have been the target of selection (e.g. in the HLA region on chromosome 6p).

Admixture in the Pre-Columbian Caribbean. 
J. C. Martinez-Cruzado et al.

The biological origin of the Caribbean aborigines that greeted Columbus is one of the most controversial issues regarding the population history of this region. Genome studies suggest an Equatorial-Tucanoan origin, consistent with the Arawakan language spoken by most natives of the region. However, the archaeological evidence suggests an early arrival from Mesoamerica, and their admixture with the more recent Arawak-speaking group stemming from the Amazon remains a possibility. The lineages comprehending most Puerto Rican samples belonging to haplogroups B1 and C1, which in turn encompass 44% of all Native American mtDNAs in the island, have an unambiguous South American origin. However, none of those belonging to haplogroup A2, encompassing 52% of all Native American mtDNAs, have been related to South America or any other continental region. To augment the scarce data from Mesoamerican countries other than Mexico, we present the complete mtDNA sequence of 6 Honduran samples belonging to distinct control region lineages in addition to 3 from the Dominican Republic and 3 from Puerto Rico. Interestingly, maximum likelihood phylogenetic reconstruction including 40 published haplogroup A2 sequence haplotypes from Mesoamerica, Central America and South America clusters 8 out of 10 Mesoamerican and Andean haplotypes in a deep rooted group, separate from, and excluding all Costa Rican, Panamian and Brasilian haplotypes, suggesting a relatively recent origin for Chibchan-Paezan and Amazonian groups. Furthermore, 4 of the 5 Greater Antillean A2 haplotypes are included in the deeply rooted Mesoamerican-Andean cluster. Moreover, the only Cuban haplotype in the literature and the remaining A2 haplotype from the Dominican Republic form even more deeply rooted private branches. Similarly, the only haplogroup C1d sample sequenced from the Dominican Republic forms a private branch with the deepest root in a maximum likelihood tree containing 19 additional C1d haplotypes from Mexico to Brasil plus the CRS. In conclusion, our preliminary results suggest that a substantial proportion of the Native American mtDNA lineages from the Greater Antilles do not share an Amazonian origin with the language their people spoke in 1492. Furthermore, the position of two Dominican lineages at the earliest split in both their respective trees suggests an early origin that could be explained by extensive lineage extinctions in Mesoamerica and the Andes or an origin in North America.

 The possible role of social selection in the distribution of the "Proto-Mongolian" haplotype in Kazakhs, Kyrgyz, Mongols and other Eurasian populations.
M. Zhabagin et al.

Social factors may be important contributors to reproductive success and determination of the selective survival of individuals. Therefore, social selection and other social factors are important for understanding population structure and its formation. The role of social selection on the distribution and formation of Y-chromosomal gene pool has been studied. There is a strong connection between social selection and birth rate of the descendants, whose fathers had achieved high social status during the expansion of the Mongol Empire and associated historical events. A total of 783 haplotypes, including 687 newly obtained and 96 retrieved from the literature were assigned to the haplogroup C3*-M217 (xM48) based on genotyping 17 Y-chromosomal STR markers. These haplotypes represent 11 populations of Eurasia: Kazakhs, Mongols, Kyrgyz, Telengits, Circassians, Balkar, Temirgoys, Karachai, Evenki, Kizhi and the Pashtuns. As the result, a major haplotype 13-16-25-15-16-18-14-10-22-11-10-11-13-10-21 (DYS389a-DYS389b-DYS390-DYS456-DYS19-DYS458-DYS437-DYS438-DYS448-GATA4-DYS391-DYS392-DYS393-DYS439-DYS635, N=94) was found to have 12.00% frequency within haplogroup C3*. This haplotype includes and extends the previously described “star-cluster” haplotype. Noteworthy, the frequency of this major haplotype within haplogroup C3* was 16.80% in Kazakhs, 10.13% in Mongols and 2.63% in Kirgiz who are not considered as direct descendants of Genghis Khan. 35.10% of the major haplotype was represented by Kazakh tribe Ashamayly-Kerey, 17.02% by the Khalkh Mongols and 7.44% by the Barguts. Therefore, we suppose this major ancestral haplotype to be the "proto-Mongolian haplotype", inherited by Genghis Khan and his descendants. It is important to mention that Temujin belongs to Kiyat-Borjigin tribe that in turn is a branch of the bigger Borjigin tribe, part of the Khalkh Mongols. Thus, Genghis Khan might be considered as a carrier rather than founder of the star-cluster haplotype. He and his descendants are the ones who contributed to a positive effect of social selection in the distribution of this haplotype. Other examples are the Barguts, who had Genghis Khan’s credit and were granted with a number of privileges, or the Kerey, based on the fact that Temujin had been brought up at the court of the Togrul Khan, belonging to the Kerey tribe.

Y-chromosomal variation in native South Americans: bright dots on a gray canvas.
M. Nothnagel et al.

While human populations in Europe and Asia have often been reported to reveal a concordance between their extant genetic structure and the prevailing regional pattern of geography and language, such evidence is lacking for native South Americans. In the largest study of South American natives to date, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other. We observed virtually no structure for the extant Y-chromosomal genetic variation of South American males that could sensibly be related to their inter-tribal geographic and linguistic relationships, augmented by locally confined Y-STR autocorrelation. Analysis of repeatedly taken random subsamples from Europe adhering to the same sampling scheme excluded the possibility that this finding was due to our specific scheme. Furthermore, for the first time, we identified a distinct geographical cluster of Y-SNP lineages C-M217 (C3*) in South America, which are virtually absent from North and Central America, but occur at high frequency in Asia. Our data suggest a late introduction of C3* into South America no more than 6,000 years ago and low levels of migration between the ancestor populations of C3* carrier and non-carriers. Our findings are consistent with a rapid peopling of the continent, followed by long periods of isolation in small groups, and highlight the fact that a pronounced correlation between genetic and geographic/cultural structure can only be expected under very specific conditions.

The timing and history of Neandertal gene flow into modern humans. 

S. Sankararaman et al.

   Previous analyses of modern human variation in conjunction with the Neandertal genome have revealed that Neandertals contributed 1-4% of the genes of non-Africans with the time of last gene flow dated to 37,000-86,000 years before present. Nevertheless, many aspects of the joint demographic history of modern humans and Neandertals are unclear. We present multiple analyses that reveal details of the early history of modern humans since their dispersal out of Africa.
   1.We analyze the difference between two allele frequency spectra in non-Africans: the spectrum conditioned on Neandertals carrying a derived allele while Denisovans carry the ancestral allele and the spectrum conditioned on Denisovans carrying a derived allele while Neandertals carry the ancestral allele. This difference spectrum allows us to study the drift since Neandertal gene flow under a simple model of neutral evolution in a panmictic population even when other details of the history before gene flow are unknown. Applying this procedure to the genotypes called in the 1000 Genomes Project data, we estimate the drift since admixture in Europeans of about 0.065 and about 0.105 in East Asians. These estimates are quite close to those in the European and East Asian populations since they diverged, implying that the Neandertal gene flow occurred close to the time of split of the ancestral populations. 
   2.Assuming only one Neandertal gene flow event in the common ancestry of Europeans and East Asians, we estimate the drift since gene flow in the common ancestral population. We show that an upper bound on this shared drift is 0.018. Because this is far less than the drift associated with the out-of-Africa bottleneck of all non-African populations, this shows that the Neandertal gene flow occurred after the out-of-Africa bottleneck. 
   3.We use the genetic drift shared between Europeans and East Asians, in conjunction with the observation of large regions deficient in Neandertal ancestry obtained from a map of Neandertal ancestry in Eurasians, to estimate the number of generations and effective population size in the period immediately after gene flow. These analyses suggest that only a few dozen Neandertals may have contributed to the majority of Neandertal ancestry in non-Africans today.

Genetic characterisation of two Greek population isolates. 

K. Hatzikotoulas et al.

   Genetic association studies of low-frequency and rare variants can be empowered by focusing on isolated populations. It is important to genetically characterize population isolates for substructure and recent admixture events as these may give rise to spurious associations. Under the auspices of the HELlenic Isolated Cohorts study (HELIC; www.helic.org) we have collected >3,000 samples from two isolated populations in Greece: the Pomak villages (HELIC Pomak), a set of religiously-isolated mountainous villages in the North of Greece; and Anogia and surrounding mountainous villages on Crete (HELIC MANOLIS). All samples have information on anthropometric, cardiometabolic, biochemical, haematological and diet-related traits. 1,500 individuals from each population isolate have been typed on the Illumina OmniExpress and Human Exome Beadchip platforms. Multidimensional scaling analysis with the 1000 Genomes Project data shows similarities of the two population isolates with Mediterranean populations such as the Tuscans from Italy and Iberians from Spain. We also observe evidence for structure within the isolates, with the Kentavros village in the Pomak strand demonstrating high levels of differentiation. To characterise the degree of isolatedness in these populations we estimated the proportion of individuals with at least one “surrogate parent” (using only the subset of samples with pairwise pi-hat<0 .2="" 707="" adolescents="" an="" and="" at="" attica="" compared="" comprises="" district.="" find="" for="" from="" genome="" greek="" in="" individuals="" is="" isolate="" least="" manolis="" of="" one="" outbred="" parent="" population="" proportion="" random="" regions="" study="" surrogate="" teenage="" that="" the="" this="" to="" unrelated="" we="" which="" with="">60% and in the Pomak isolate is >65% compared to ~1% in the outbred Greek population. Our results establish these populations as isolates and provide some insights into the genomic architecture of Greek populations, which have not been previously characterised.

Efficient and Accurate Whole-Genome Human Phasing.
T. Blauwkamp et al.

   High throughput DNA sequencing allows whole human genomes to be resequenced rapidly and inexpensively producing a comprehensive list of variants relative to the reference genome. However, short read sequencing technologies are limited in their ability to determine phasing information, thus resulting in heterozygous calls being represented as the average of the maternal and paternal chromosomes. Phasing information is of critical importance to personal medicine as it provides a better linkage between genotype and phenotype, permitting new advances in our understanding of compound heterozygote linked diseases, pharmacogenomics, HLA typing, and prenatal genome sequencing. Here, we describe a new sample prep method that enables whole human genome haplotyping at high accuracy using only 30Gb of sequence data. Genomic DNA was fragmented into ~10Kb fragments, end repaired, and ligated to adapters. Hundreds of aliquots with approximately 50MB of DNA in each were amplified, fragmented and converted into individual shotgun libraries. The pooled libraries were sequenced in a single lane of a HiSeq2500 at 2x100bp to generate ~30Gb of sequence. The resulting sequence information was analyzed to obtain a set of long blocks of ~10Kb, covering multiple heterozygous SNPs, allowing phasing of these SNPs relative to each other. An HMM-based phasing algorithm was used to compute the most likely phase and confidence intervals based on the observed coverage and sequencer quality scores. Phasing of those blocks relative to each other was done by another HMM-based algorithm which uses a panel of previously phased genomes. Comparing our results with phase information inferred by transmission from the parents, we found that over 98% of heterozygous SNPs were phased within long blocks (N50=500kb) at a switch error rate below 1 switch per megabase of phased sequence. We present results obtained from multiple cell lines and human samples. This new library prep method and data analysis pipeline enables whole human genome phasing with only 30Gb of raw sequence, which represents only ~30% more sequencing than current 30x baseline run for human sequencing. Compared to other published reports, this method is capable of phasing a greater fraction of SNPS with ~75% less sequencing. Coupling our higher percentage of SNPs phased with high accuracy and the lowest sequencing requirement, this new technology is the most affordable approach to generating completely phased whole human genomes.

 Inference of Natural Selection and Demographic History for African Pygmy Hunter-Gatherers.
P. H. Hsieh et al.

   African Pygmies are hunter-gatherers primarily inhabiting the Central African rainforests, where they are exposed to high temperatures, high humidity, and a pathogen and parasite-enriched woody habitat. These factors undoubtedly influenced their evolutionary history as they adapted to this environment. Many Pygmy populations have historically been in socio-economic contact with neighboring Niger-Kordofanian speaking farmer populations, particularly since the agriculture expansion in sub-Saharan Africa that began five thousand years ago (kya). To look for the true signatures of adaptation to the rainforest habitat of pygmies we must control for this complex demographic history. We sequenced and combined 40x whole genome sequence data from 3 Baka pygmies from Cameroon, 4 Biaka pygmies from the Central African Republic, and 9 Niger-Kordofanian speaking Yoruba farmers from Nigeria. We used ?a?i, a model-based demographic inference tool, to infer the history of these populations. Our best-fit model suggests that the ancestors of the farmer and pygmy populations diverged 150 kya and remained isolated from each other until 40 kya. This divergence is more ancient than estimated by previous studies that included fewer loci, but is consistent with a PSMC analysis, a separate inference tool that uses different aspects of the genomic data than ?a?i. Interestingly, our analysis shows that models with bi-directional asymmetric gene flow between farmers and pygmies are statistically better supported than previously suggested models with a single wave of uni-directional migration from farmers to pygmies. To identify possible targets of positive selection, we conducted a genomic scan using complementary methods, including the frequency-spectrum based G2D test, the population differentiation based XP-CLR test, and the haplotype based iHS test. We performed 10,000 simulations based on the above best-fit demographic model in order to assign statistical significance to each reported target of natural selection. Our results reveal that genes involved in cell adhesion, cellular signaling, olfactory perception, and immunity were likely targeted by natural selection in the pygmies or their recent ancestors. Our analysis also shows that genes involved in the function of lipid binding are enriched in highly differentiated non-synonymous mutations, suggesting that this function may have acted differently on the Pygmies and farmers after their divergence from their common ancestor.

Population demography and maternal history of Oceania.
A. T. Duggan et al.

   We present a large-scale study of mtDNA diversity across Near and Remote Oceania with whole-genome mtDNA sequencing and a sample collection of more than 1,300 individuals spanning from the Bismarck Archipelago in the west to the Cook Islands in the east. As the location of at least two major migration events (initial colonization over 40,000 years ago, followed by an expansion of Austronesian-speaking migrants around 3,500 years ago), Oceania provides a unique opportunity to study the effects of population admixture. Our results support the idea of sex-biased admixture between the resident populations and the migrants of the Austronesian expansion. We find that haplogroups of putative Asian origin which are thought to have spread with the Austronesian expansion are found at high frequency in all but two populations and, in general, we see little evidence of distinction between Papuan and Austronesian speaking populations. Santa Cruz, which is part of the Solomon Islands but geographically distinct from the main island chain and considered part of Remote Oceania, has long been considered a linguistic oddity and is now accepted to represent a very deep branch in the Oceanic language family. We find that it is also a genetic outlier, with potential direct connections to the Bismarck Archipelago not evident in the main Solomon Islands chain. In this expanded dataset, we find additional evidence of instability and increased heteroplasmy at the ‘Polynesian motif’ position 16247, further confirming previous findings restricted to the Solomon Islands. 

 Reconstructing Austronesian population history. 
M. Lipson et al.

   Present-day populations that speak Austronesian languages are spread across half the globe, from Easter Island in the Pacific Ocean to Madagascar in the Indian Ocean. Evidence from linguistics and archaeology suggests that the "Austronesian expansion," a vast cultural and linguistic dispersal that began 4--5 thousand years ago, had its origin in Taiwan. However, genetic studies of Austronesian ancestry have been inconclusive, with some finding affinities with aboriginal Taiwanese, others advancing an autochthonous origin within Island Southeast Asia, and others proposing a model involving multiple waves of migration from Asia. Here, we analyze genome-wide data from a diverse set of 31 Austronesian-speaking and 25 other groups typed at 18,412 overlapping single nucleotide polymorphisms (SNPs) to trace the genetic origins of Austronesians. We use a recently developed computational tool for building phylogenetic models of population relationships incorporating the possibility of admixture, which allows us to infer ancestry proportions and sources of genetic material for 26 admixed Austronesian-speaking populations. Our analysis provides strong confirmation of widespread ancestry of Taiwanese origin: at least a quarter of the genetic material in all Austronesian-speaking populations that we studied---including all of the Asian ancestry in populations from eastern Indonesia and Oceania---is more closely related to aboriginal Taiwanese than to any populations we sampled from the mainland. Surprisingly, we also show that western Austronesian-speaking populations have inherited substantial proportions of their Asian ancestry from a source that falls within the variation of present-day Austro-Asiatic populations in Southeast Asia. No Austro-Asiatic languages are spoken in Island Southeast Asia today, although there are some linguistic and archaeological suggestions of an early connection between mainland and island populations. The most plausible explanation for these findings, in light of the historical evidence, is that western Island Southeast Asia was settled by Austronesian groups who had previously mixed with Austro-Asiatic speakers on the mainland.

 No significant differences in the accumulation of deleterious mutations across diverse human populations. 
R. Do et al.

   Differences in demographic history across populations are expected to cause differences in the accumulation of deleterious mutations because natural selection works less efficiently when population sizes are small. Surprisingly, however, the relative burden of deleterious mutations has never been directly measured across human populations on a per-haploid genome basis, despite the fact that this is what matters biologically in the absence of dominance and epistasis. Here we empirically measure the relative accumulation of deleterious mutations in 13 diverse populations (Yoruba, Mandenka, San, Mbuti, Dinka, Australian, French, Sardinian, Han, Dai, Mixe, Karitiana and Papuan) along with one archaic population (Denisova). All the present-day populations have statistically indistinguishable accumulations of coding mutations. We highlight two examples. First, we find no evidence for a lower mutational load in West Africans than in Europeans despite the approximately 30% higher genetic diversity in West Africans: the accumulation of nonsynonymous mutations in West Africans is 1.01±0.02 times that in Europeans, and for “probably damaging” mutations, the ratio is 1.03±0.04. Second, we find no evidence for a lower mutational load in populations that have experienced agriculture-related expansions over the last 10,000 years and those that have not: the ratio in Chinese to Karitiana hunter gatherers from Brazil is 0.99±0.07. We determined that these null results are not an artifact of insensitivity of our method to differences in demographic history. As a positive control, we also analyzed archaic Denisovans who are known to have had a small population size for hundreds of thousands of years since separation from modern humans. We show that the Denisovan lineage has accumulated “probably damaging” mutations 1.33±0.06 times more rapidly than modern humans since they split. These analyses are important because of the new constraints they place on the distribution of selection coefficients in humans. Given the currently estimated demographic histories of West Africans and Europeans, combined with the fact that we do not detect a lower accumulation of deleterious mutations in West Africans than Europeans, we can conclude that only a small proportion of nonsynonymous mutations have selection coefficients in the range s=-0.01 to -0.001, which is the range of selection coefficients which would be expected to show a lower accumulation in West Africans than in Africans.

Deep coverage Bedouin genomes reveal Bedouin haplotypes shared among worldwide populations in the 1000 Genomes Project. 
J. L. Rodriguez-Flores et al.

   The 1000 Genomes Project (1000G) has sampled and sequenced over 2500 genomes that are representative of the genetic diversity in populations worldwide. The Arabian Peninsula has not been previously included in 1000G, hence the connections between genetic variation in the indigenous Bedouin people and worldwide populations is unknown. We have sampled genomes from Bedouin individuals in the nation of Qatar as a window into the genetic variation in this understudied region. Our goal was to use this sample to assess the hypothesis that there is detectable shared ancestry between Bedouin and Southern European populations resulting from the history of empires that spanned both the Mediterranean and Arabian regions and the hypothesis that there is shared ancestry between Bedouin and contemporary Latin American populations, since the majority of European settlers in Latin America from the past half millennia are primarily from Southern European countries. We selected 60 Qataris with over 95% Bedouin ancestry and at least 3 generations of ancestry in Qatar for deep coverage genome sequencing. Genomes were sequenced by the Illumina Genome Network using TruSeq DNA PCR-free sample preparation, generating over 120 gigabases of paired-end 100 base pair reads per genome on a HiSeq 2500, yielding over 30x depth and genotypes for >96% of the genome using both the ELAND/CASAVA and BWA/GATK pipelines. Using these genotypes, we inferred haplotypes using SHAPEIT for Bedouin Qataris and for 1000G populations on a set of sites polymorphic in both 1000G and Bedouins. We used admixture analysis to assess shared ancestry between our Bedouin sample and 1000G populations using the ancestry deconvolution method SUPPORTMIX. Given the lack of appropriate ancestral populations, we conducted a leave-one-out approach, where for each population (1000G + Bedouin = n), we removed the population and used the remaining n-1 populations as an ancestral reference panel. Using this approach, we observed up to 15% Bedouin ancestry in European, South Asian, and American populations. Likewise, we observed ancestry from Europe, South Asia, and America in the Bedouin. For individuals from the Americas, the analysis identified a considerable number of segments shared with Bedouins previously classified as European ancestry. 

Using a haplotype-based model to infer Native American colonization history.
C. Lewis et al.

   We apply a powerful haplotype-based model (described in Lawson et al. 2012) to infer the population history of 410 individuals from ~50 Native American groups, using data interrogated at >470,000 genome-wide autosomal Single-Nucleotide-Polymorphisms (SNPs). The model matches haplotype patterns among individuals' chromosomes to infer which individuals share recent common ancestry at each location of the genome, an approach that has previously been demonstrated to increase power substantially over widely-used alternative approaches that consider SNPs independently. We apply this methodology to 1861 samples described in Reich et al. (2012), incorporating 263 additional samples from 32 relevant world-wide regions collated from other publicly available resources and currently unavailable data. We utilize these methodology and data in two ways. First, we infer intermixing (i.e. "admixture") events among different Native American groups by identifying the groups that share the most haplotype segments. Using additional unpublished techniques, we determine the dates of these intermixing events, the proportions of DNA contributed, and the precise genetic make-up of the groups involved. These unique characteristics set this methodology apart from all presently available software, allowing us to place these mixing events into a clear historical context and thus identify the factors (e.g. the rise or fall of various Native American empires) that have contributed most to the genetic architecture of present-day Native American groups. Second, we match DNA patterns from each Native American group to a set of over 30 populations from Siberia and East Asia, describing each Native American group as a mixture of DNA from these regions. This enables us to shed light on the widely debated number of distinct migrations into the Americas during the initial colonization across the Bering Strait, comparing our results to previous inference from the literature. Our application demonstrates the power gained by using rich haplotype information relative to approaches that ignore this information.

Using Ancient Genomes to Detect Positive Selection on the Human Lineage. 

K. Prüfer et al.

   At least two distinct groups of archaic hominins inhabited Eurasia before the arrival of modern humans: Neandertals and Denisovans. The analysis of the genomes of these archaic humans revealed that they are more closely related to one another than they are to modern humans. However, since modern and archaic humans are so closely related, only about 10% of the archaic DNA sequences fall outside the present-day human variation whereas for 90% of the genome, Neandertal or Denisova DNA sequences are more closely related to some humans than to others. The fact that the archaic sequence often falls within the diversity of modern humans can be used to detect selective sweeps that affected all modern humans after their split from archaic humans since such sweeps will result in genomic regions where both the Neandertal and Denisova genomes fall outside the modern human variation. The genetic lengths of such external regions are proportional to the strength of selection, since stronger selection will lead to faster sweeps allowing less time for recombination to decrease their size. We have implemented a test for such external regions as a hidden Markov model. At each polymorphic position the model emits ancestral or derived based on whether the tested archaic genome carries the ancestral or derived variant of SNPs observed in present-day humans. The model was applied to 185 African genomes from the 1000 genomes phase 1 data. We identified thousands of external regions using the Neandertal and Denisova genomes, separately. Approximately one third of the regions are overlapping between the two genomes. These regions are significantly longer than regions only identified in only one of the archaic genomes. Based on this excess of overlap for long regions, we devise a measure to identify a set of regions that are candidates for selective sweeps on the human lineage since the split from Neandertal and Denisova.

Pulling out the 1%: Whole-Genome In-Solution (WISC) capture for the targeted enrichment of ancient DNA sequencing libraries. 

C. D. Bustamante et al.

   The very low levels of endogenous DNA remaining in most ancient specimens has precluded the shotgun sequencing of many interesting samples due to cost. For example, ancient DNA (aDNA) libraries derived from bones and teeth often contain <1 b="" by="" capacity="" dna.="" dna="" endogenous="" environmental="" is="" majority="" meaning="" of="" sequencing="" taken="" that="" the="" up=""> We will present a method for the targeted enrichment of the endogenous component of human aDNA sequencing libraries. Using biotinylated RNA baits transcribed from genomic DNA libraries, we are able to significantly enrich for human-derived DNA fragments. This approach, which we call whole-genome in-solution capture (WISC), allows us to obtain genome-wide ancestral information from ancient samples with very low endogenous DNA contents. We demonstrate WISC on libraries created from four Iron Age and Bronze Age human teeth from Bulgaria, as well as bone samples from seven Peruvian mummies and a Bronze Age hair sample from Denmark. Prior to capture, shotgun sequencing of these libraries yielded an average of 1.2% of reads mapping to the human genome (including duplicates). After capture, this fraction increased dramatically, with up to 59% of reads mapped to human and folds enrichment ranging from 5X to 139X. Furthermore, we maintained coverage of the majority of fragments present in the pre-capture library. Intersection with the 1000 Genomes Project reference panel yielded an average of 50,723 SNPs (range 3,062-147,243) for the post-capture libraries sequenced with 1 million reads, compared with 13,280 SNPs (range 217-73,266) for the pre-capture libraries, increasing resolution in population genetic analyses. We will also present the results of performing WISC on other aDNA libraries from both archaic human and non-human samples, including ancient domestic dog samples. Our capture approach is flexible and cost-effective, allowing researchers to access aDNA from many specimens that were previously unsuitable for sequencing. Furthermore, this method has applications in other contexts, such as the enrichment of target human DNA in forensic samples.

Insights into population history from a high coverage Neandertal genome. 

D. Reich1, for.the. Neandertal Genome Consortium2 

   We have sequenced to about 50-fold coverage a genome sequence from about 40 mg of a bone found in Denisova Cave in Southern Siberia. The genome of this female is much more closely related to the low-coverage Neandertal genomes from Croatia, Spain, Germany and the Caucasus than to the genome of archaic Denisovans, a sister group of Neandertals, and provides unambiguous evidence that both Neandertals and Denisovans inhabited the Altai Mountains in Siberia. The high-coverage Neandertal genome, combined with our earlier sequencing of a high quality Denisova genome, allows novel insights about the population history of archaic humans:
    •We document recent inbreeding in this Altai Neandertal. The inbreeding coefficient of about 1/8 corresponds to about the homozygosity that would be expected from a mating of half siblings. 
    •The Altai Neandertal genome shares almost seven percent more derived alleles with present-day Africans than does the Denisova genome. This means that the Denisovans derived a proportion of their ancestry from a very archaic human lineage, and the amount of this ancestry they inherit is larger than in Neandertals. 
    • The Denisovan genome is affected by major recent gene flow from an Altai-related Neandertal. 
    • To further characterize the variation among Neandertals we sequenced the genome of a Neandertal from the Caucasus to about 0.5-fold coverage. Comparisons to present-day genomes show that the Neandertals who contributed genes to present-day non-Africans were more closely related to this Caucasian Neandertal than to the Neandertals we sequenced from the Altai. 
    •We built a map of Neandertal ancestry in modern humans, using data from all non-Africans in the 1000 Genomes Project. We show that the average Neandertal ancestry on chromosome X of present-day non-Africans is about a fifth of the genome average. It is known that hybrid incompatibility loci concentrate on chromosome X. Thus, this observation is consistent with a model of hybrid incompatibility in which Neandertal variants that introgressed into modern humans were rapidly selected away due to epistatic interactions with the modern human genetic background.

Inferring complex demographies from PSMC coalescent rate estimates: African substructure and the Out-of-Africa event.
S. Gopalakrishnan et al.

   Human population history is an intriguing and complex story with many events like population growth, bottlenecks, time-dependent/non-homogeneous migration, population splits and mixtures. Estimating complete demographies with population sizes, rates of gene flow and population split times has proven to be a challenging endeavor. We propose a framework for jointly estimating the demography parameters, especially gene-flow rates and split times, for a large number of populations. We use coalescent rate estimates obtained from Pairwise Sequentially Markovian Coalescent (PSMC) as the starting point for our analysis. Since PSMC works on only two chromosomes at a time, we apply PSMC to all pairs of individuals to obtain the pairwise coalescent rates for lineages from every pair of sampled populations. Using a mathematical model for calculating coalescent probabilites given population parameters, we estimate demography using the parameters that best fit the observed coalesecent rates.
   In this study, we focus on two aspects of African population genetics, 1. the nature of population structure in Africa going back in time and 2. the timing of the Out-of-Africa event. To address these questions, we assembled a dataset with whole genome sequences from 162 individuals using both in-house sequencing and publicly available sources. These samples span 22 populations worldwide. These include eleven African populations which we use to dissect the population substructure in Africa. In addition, we also have 2 Middle Eastern, 5 European and 4 East/Central Asian populations which inform the population split time estimates for the Out-of-Africa event and the European-Asian split.
   We find extensive population structure in Africa extending back to before the Out-of-Africa event. The Ethiopian populations, Amhara and Oromo, show evidence of mixing beyond 15 kya. The Maasai and Luhye merge with the Ethiopian populations to form a panmictic East African population ~40kya. We find evidence for extensive mixing between east and west African populations before 50kya. Among the pygmy populations, we see recent gene flow between the Batwa and Mbuti. All African populations except the San merge into a single population around 110 kya. The San exchange migrants with the other African populations beginning ~120 kya. We estimate the Out-of-Africa event to have occurred ~75kya and the European-Asian split to ~25kya.

Out of Africa, which way? 
L. Pagani et al.

While the African origin of all modern human populations is well-established, the dynamics of the diaspora that led anatomically modern humans to colonize the lands outside Africa are still under debate. Understanding the demographic parameters as well as the route (or routes) followed by the ancestors of all non-Africans could help to refine our understanding of the selection processes that occurred subsequently, as well as shedding light on a landmark process in our evolutionary history. Of the three possible gateways out of Africa (via Morocco across the Gibraltar strait, via Egypt through the Suez isthmus or via the Horn of Africa across Bab el Mandeb strait) only the latter two are supported by paleoclimatic and archaeological evidence. Furthermore, recent studies (Pagani et al. 2012) showed that, although the modern Ethiopian populations might be good candidates for the descendants of the source population of such a migration, modern Egyptians could be an even better candidate. Unfortunately, however, only a few Egyptian samples have been genotyped and, as yet, none have been fully sequenced. Here, we have generated 125 Ethiopian and 100 Egyptian whole genome sequences (Illumina HiSeq, 8x average depth). The genomes were partitioned using PCAdmix (Brisbin et al. 2012) to account for the confounding effects of recent introgression from neighboring non-African populations. To explore the genetic legacy of migration routes out of Africa, and in particular to test whether the observed genetic data support one route over another, the African components of Egyptians and Ethiopians were then compared to a panel of available non-African populations from the 1000 Genomes Project (1000 Genomes Project Consortium, 2012). The high resolution provided by whole genome sequencing allows us to shed new light on the paths followed by our ancestors as they left Africa, as well as refining the current knowledge of the demographic history of the populations analyzed.

The Saudi Arabian Genome Reveals a Two Step Out-of-Africa Migration. 

J. J. Farrell et al.

   Here we present the first high-coverage whole genome sequences from a Middle Eastern population consisting of 14 Eastern Province Saudi Arabians. Genomes from this region are of interest to further answer questions regarding “Out-of-Africa” human migration. Applying a pairwise sequentially Markovian coalescent model (PSMC), we inferred the history of population sizes between 10,000 years and 1,000,000 years before present (YBP) for the Saudi genomes and an additional 11 high-coverage whole genome sequences from Africa, Asia and Europe.
   The model estimated the initial separation from Africans at approximately 110,000 YBP. This intermediate population then underwent a long period of decreasing population size culminating in a bottleneck 50,000 YBP followed by an expansion into Asia and Europe. The split and subsequent bottleneck were thus two distinct events separated by a long intermediate period of genetic drift in the Middle East. The two most frequent mitochondria haplogroups (30% each) were the Middle Eastern U7a and the African L. The presence of the L haplogroup common in Africa was unexpected given the clustering of the Saudis with Europeans in the phylogenetic tree and suggests some recent African admixture. To examine this further, we performed formal tests for a history of admixture and found no evidence of African admixture in the Saudi after the split. Taken together, these analyses suggest that the L3 haplogroup found in the Saudi were present before the bottleneck 50,000 YBP. Given the TMRCA estimates for the L3 haplogroup of approximately 70,000 YBP and the timing of the Out-of-Africa split, these analyses suggest that L3 haplogroup arose in the Middle East with a subsequent back migration and expansion into Africa over the Horn-of-Africa during the lower sea levels found during the glacial period bottleneck.
    These results are consistent with the hypothesis that modern humans populated the Middle East before a split 110,000 YBP, underwent genetic drift for 60,000 years before expanding to Asia and Europe as well as back-migration into Africa. Examination of genetic variants discovered by Saudi whole genome sequencing in ancestral African populations and European/Asian populations will contribute to the understanding human migration patterns and the origin of genetic variation in modern humans.

 Geographic Population Structure (GPS) of worldwide human populations infers biogeographical origin down to home village
E. Elhaik et al.

The search for a method that utilizes biological information to predict human’s place of origin has occupied scientists for millennia. Modern biogeography methods are accurate to 700 km in Europe but are highly inaccurate elsewhere, particularly in Southeast Asia and Oceania. The accuracy of these methods is bound by the choice of genotyping arrays, the size and quality of the reference dataset, and principal component (PC)-based algorithms. To overcome the first two obstacles, we designed GenoChip, a dedicated genotyping array for genetic anthropology with an unprecedented number of ~12,000 Y-chromosomal and ~3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPs carefully chosen to study ancestry without any known health, medical, or phenotypic relevance. We also 615 individuals from 54 worldwide populations collected as part of the Genographic Project and the 1000 Genomes Project. To overcome the last impediment, we developed an admixture-based Geographic Population Structure (GPS) method that infers the biogeography of worldwide individuals down to their village of origin. GPS’s accuracy was demonstrated on three data sets: worldwide populations, Southeast Asians and Oceanians, and Sardinians (Italy) using 40,000-130,000 GenoChip markers. GPS correctly placed 80%; of worldwide individuals within their country of origin with an accuracy of 87%; for Asians and Oceanians. Applied to over 200 Sardinians villagers of both sexes, GPS placed a quarter of them within their villages and most of the remaining within 50 km of their villages, allowing us to identify the demographic processes that shaped the Sardinian society. These findings are significantly more accurate than PCA-based approaches. We further demonstrate two GPS applications in tracing the poorly understood biogeographical origin of the Druze and North American (CEU) populations. Our findings demonstrate the potential of the GenoChip array for genetic anthropology. Moreover, the accuracy and power of GPS underscore the promise of admixture-based methods to biogeography and has important ramifications for genetic ancestry testing, forensic and medical sciences, and genetic privacy.