Neandertal admixture in modern humans: some of it adaptive, some selected-against (Sankararaman et al. 2014)

From this paper, this should be of interest for those who argue if they are .1 or .2% more/less Neandertal than others based on commercial testing results:

Fourth, the standard deviation in Neanderthal ancestry among individuals from within the same population is 0.06–0.10%, in line with theoretical expectation (Supplementary Information section 3), showing that Neanderthal ancestry calculators that estimate differences on the order of a per cent18 are largely inferring statistical noise.

Also of interest, showing that while overall Neandertal ancestry in Eurasians is low (1+%), this average includes region where it is much higher, and indeed the majority:

The Neanderthal introgression map reveals locations where Neanderthal ancestry is inferred to be as high as 62% in east-Asian and 64% in European populations (Fig. 1b and Extended Data Fig. 2).

Finally:

We have shown that interbreeding of Neanderthals and modern humans introduced alleles onto the modern human genetic background that were not tolerated, which probably resulted in part from their contributing to male hybrid sterility. The resulting reduction in Neanderthal ancestry was quantitatively large: in the fifth of the genome with highest B, Neanderthal ancestry is 1.5460.15 times the genomewide average (Extended Data Table 4 and Supplementary Information section 9)22. If we assume that this subset of the genome was unaffected by selection, this implies that the proportion of Neanderthal ancestry shortly after introgression must have been >3%rather than the approximately 2% seen today. 

One of the lingering questions about Neandertal admixture is why there are no Neandertal Y-chromosomes or mtDNA in modern Eurasians. The disappearance of Neandertal mtDNA seems unlikely according to one study, but might be explained if negative selection was at play.

A different question is whether hybrid sterility was actually noticed by modern humans/Neandertals during the period of admixture. Modern societies have historically frowned upon mixture between diverged sapiens populations, even though there is no evidence that the offspring of, say, an African and a European are biologically disadvantaged. But, in the case of sapiens-Neandertal crossings, the offspring would have been biologically disadvantaged, a fact that may have been noticed over the span of a few generations.

Regardless of the historical dynamics of the admixture process, some of the Neandertal genome proved itself useful in its new sapiens hosts, and while the process may have been painful for the people involved, evolution found a way to use at least some of the material introduced to our species by our Neandertal cousins.

Nature (2014) doi:10.1038/nature12961

The genomic landscape of Neanderthal ancestry in present-day humans

Sriram Sankararaman

Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture1, 2. The antiquity of Neanderthal gene flow into modern humans means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci1, 3, 4, 5, 6, 7, 8. We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans9. Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes10, 11, 12. These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.

Link

Paternal and maternal demographic histories (Lippold et al. 2014)

A new preprint on the bioRxiv on the different male/female demographic history of humans.

Red=female, blue=male.

This is probably related to the new paper on selection on the Y chromosome which interprets reduced diversity as evidence for selection.

doi: 10.1101/001792

Human paternal and maternal demographic histories: insights from high-resolution Y chromosome and mtDNA sequences 

Sebastian Lippold et al.

To investigate in detail the paternal and maternal demographic histories of humans, we obtained ~500 kb of non-recombining Y chromosome (NRY) sequences and complete mtDNA genome sequences from 623 males from 51 populations in the CEPH Human Genome Diversity Panel (HGDP). Our results: confirm the controversial assertion that genetic differences between human populations on a global scale are bigger for the NRY than for mtDNA; suggest very small ancestral effective population sizes (less than 100) for the out-of-Africa migration as well as for many human populations; and indicate that the ratio of female effective population size to male effective population size (Nf/Nm) has been greater than one throughout the history of modern humans, and has recently increased due to faster growth in Nf. However, we also find substantial differences in patterns of mtDNA vs. NRY variation in different regional groups; thus, global patterns of variation are not necessarily representative of specific geographic regions.

Link

Arabian origin of the Upper Paleolithic in the Levant

This is a very useful review of research on the origin of the Upper Paleolithic (Emiran) in the Levant, arguing against a recent (c. 50kya ) African origin and in favor of an Arabian one. The argument is mainly archaeological, although it is informed by genetic evidence. From the chapter:

After a century of research, the origins of the Levantine UP still remain an enigma. At this point, at least one thing is clear: the Emiran has no African progenitor. As such, there is a disconnect between the archaeological database and the Replacement paradigm, which necessitates that the earliest Levantine Upper Paleolithic must have come fully developed from northeast Africa. The Replacement model should have been a parsimonious prism through which to view the transition from the MP to the UP in the Levant. It was not.

The recent acceptance of: (i) a slower autosomal mutation rate, and (ii) evidence for interbreeding with Neandertals largely predating the c. 50kya mark, and (iii) coalescence of Eurasian mtDNA haplogroup N well before that time, have all but killed, in my opinion the idea of a 50kya spread of modern humans from Africa. Modern humans must have lived in Eurasia much earlier than that time, and what remains is to figure out how much earlier.

A century of research into the origins of the Upper Palaeolithic in the Levant

Anthony E. Marks and Jeffrey I. Rose

Link

Tuberculosis and Out of Africa

Nature Genetics 45, 1176–1182 (2013) doi:10.1038/ng.2744

Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans

Iñaki Comas et al.

Tuberculosis caused 20% of all human deaths in the Western world between the seventeenth and nineteenth centuries and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. We analyzed the whole genomes of 259 M. tuberculosis complex (MTBC) strains and used this data set to characterize global diversity and to reconstruct the evolutionary history of this pathogen. Coalescent analyses indicate that MTBC emerged about 70,000 years ago, accompanied migrations of anatomically modern humans out of Africa and expanded as a consequence of increases in human population density during the Neolithic period. This long coevolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low and high host densities.

Link

Chronology of Ksar Akil

PLoS ONE 8(9): e72931. doi:10.1371/journal.pone.0072931

Chronology of Ksar Akil (Lebanon) and Implications for the Colonization of Europe by Anatomically Modern Humans

Katerina Douka et al.

The Out-of-Africa model holds that anatomically modern humans (AMH) evolved and dispersed from Africa into Asia, and later Europe. Palaeoanthropological evidence from the Near East assumes great importance, but AMH remains from the region are extremely scarce. ‘Egbert’, a now-lost AMH fossil from the key site of Ksar Akil (Lebanon) and ‘Ethelruda’, a recently re-discovered fragmentary maxilla from the same site, are two rare examples where human fossils are directly linked with early Upper Palaeolithic archaeological assemblages. Here we radiocarbon date the contexts from which Egbert and Ethelruda were recovered, as well as the levels above and below the findspots. In the absence of well-preserved organic materials, we primarily used marine shell beads, often regarded as indicative of behavioural modernity. Bayesian modelling allows for the construction of a chronostratigraphic framework for Ksar Akil, which supports several conclusions. The model-generated age estimates place Egbert between 40.8–39.2 ka cal BP (68.2% prob.) and Ethelruda between 42.4–41.7 ka cal BP (68.2% prob.). This indicates that Egbert is of an age comparable to that of the oldest directly-dated European AMH (Peştera cu Oase). Ethelruda is older, but on current estimates not older than the modern human teeth from Cavallo in Italy. The dating of the so-called “transitional” or Initial Upper Palaeolithic layers of the site may indicate that the passage from the Middle to Upper Palaeolithic at Ksar Akil, and possibly in the wider northern Levant, occurred later than previously estimated, casting some doubts on the assumed singular role of the region as a locus for human dispersals into Europe. Finally, tentative interpretations of the fossil's taxonomy, combined with the chronometric dating of Ethelruda's context, provides evidence that the transitional/IUP industries of Europe and the Levant, or at least some of them, may be the result of early modern human migration(s).

Link

Rivers across the Sahara

PLoS ONE 8(9): e74834. doi:10.1371/journal.pone.0074834

Were Rivers Flowing across the Sahara During the Last Interglacial? Implications for Human Migration through Africa

Tom J. Coulthard et al.

Human migration north through Africa is contentious. This paper uses a novel palaeohydrological and hydraulic modelling approach to test the hypothesis that under wetter climates c.100,000 years ago major river systems ran north across the Sahara to the Mediterranean, creating viable migration routes. We confirm that three of these now buried palaeo river systems could have been active at the key time of human migration across the Sahara. Unexpectedly, it is the most western of these three rivers, the Irharhar river, that represents the most likely route for human migration. The Irharhar river flows directly south to north, uniquely linking the mountain areas experiencing monsoon climates at these times to temperate Mediterranean environments where food and resources would have been abundant. The findings have major implications for our understanding of how humans migrated north through Africa, for the first time providing a quantitative perspective on the probabilities that these routes were viable for human habitation at these times.

Link

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.

The Origin of Us

A whole bunch of very interesting videos have been posted on youtube from this interesting symposium that took place this May. A few that caught my eye:

CARTA: The Origin of Us - Fossils of Modern Humans Interbreeding within and outside of Africa
CARTA: The Origin of Us -- Richard Ed Green: Interbreeding with Archaic Humans outside Africa
CARTA: The Origin of Us -- Christopher Ehret: Relationships of Ancient African Languages
CARTA: The Origin of Us -- Chris Stringer: Fossil Record of Anatomically Modern Humans
CARTA: The Origin of Us--Rick Potts: African Climate of the Last 400000 Years
CARTA: The Origin of Us -- Ofer Bar-Yosef: Evidence for the Spread of Modern Humans
CARTA: The Origin of Us -- Michael Hammer: Interbreeding with Archaic Humans in Africa

This should be very interesting watching. Feel free to leave a comment if you notice anything new or interesting in any of the videos.

3.4-7.9% Neandertal admixture in Eurasia ?

A new paper was posted on the arXiv.
UPDATE (Feb 18, 2014): This has now been published in Genetics.

arXiv:1307.8263 [q-bio.PE]

Maximum likelihood evidence for Neandertal admixture in Eurasian populations from three genomes

Konrad Lohse, Laurent A.F. Frantz

Although there has been much interest in estimating divergence and admixture from genomic data, it has proven difficult to distinguish gene flow after divergence from alternative histories involving structure in the ancestral population. The lack of a formal test to distinguish these scenarios has sparked recent controversy about the possibility of interbreeding between Neandertals and modern humans in Eurasia. We derive the probability of mutational configurations in non-recombining sequence blocks under alternative histories of divergence with admixture and ancestral structure. Dividing the genome into short blocks makes it possible to compute maximum likelihood estimates of parameters under both models. We apply this method to triplets of human Neandertal genomes and quantify the relative support for models of long-term population structure in the ancestral African popuation and admixture from Neandertals into Eurasian populations after their expansion out of Africa. Our analysis allows us -- for the first time -- to formally reject a history of ancestral population structure and instead reveals strong support for admixture from Neandertals into Eurasian populations at a higher rate (3.4%-7.9%) than suggested previously.

Link

Middle Paleolithic and Neolithic occupations around Mundafan palaeolake (Crassard et al. 2013)

From the paper:

Survey in the Mundafan palaeolake basin revealed, for the first time, Middle Palaeolithic occupations. Recovery of Middle Palaeolithic assemblages corresponds with recent environmental and geoarchaeological studies that indicate at least three lacustrine wet phases in MIS 5 [23]. The main diagnostic lithic technology observed is the preferential Levallois reduction method, which is also present at the Jubbah palaeolake during MIS 5 (JQ-1, JSM-1 and JKF-1 sites: [21], [22]) and at the Jebel Faya rock shelter at the transition between MIS 6–5e (Assemblage C: [6]). This technology is absent in MIS 3 in southwest Yemen (SD1, SD2 and AS1 sites: [8], [9]). Earlier dating for preferential Levallois in Arabia, in MIS 7, is possible, but still insufficiently represented owing to small sample size at the Jubbah palaeolake (JQ-1: [22]). Other preferential Levallois methods have been observed in Dhofar, including in the Nubian Complex, dated to at least ca. 106 ka [7], in Hadramawt and the southern fringe of the Rub’ al-Khali, Oman [10], and in central Saudi Arabia at Al-Kharj [75]. Nubian Complex technology has not yet been identified at Mundafan. We associate the Levallois component in Mundafan with the wet pluvials of MIS 5, most probably during the wetter events of MIS 5e (ca. 125 ka), MIS 5c (ca. 100 ka) and MIS 5a (80 ka), when conditions were more favorable for hominin dispersals. The Middle Palaeolithic evidence thus provides empirical support for Rosenberg and colleagues assertion [23] that the dispersal of hominins into the Rub’ al-Khali occurred during ameliorated periods, and perhaps supports their claim for the expansion of Homo sapiens into this marginal environment.

PLoS ONE 8(7): e69665. doi:10.1371/journal.pone.0069665

Middle Palaeolithic and Neolithic Occupations around Mundafan Palaeolake, Saudi Arabia: Implications for Climate Change and Human Dispersals

Rémy Crassard et al.

The Arabian Peninsula is a key region for understanding climate change and human occupation history in a marginal environment. The Mundafan palaeolake is situated in southern Saudi Arabia, in the Rub’ al-Khali (the ‘Empty Quarter’), the world’s largest sand desert. Here we report the first discoveries of Middle Palaeolithic and Neolithic archaeological sites in association with the palaeolake. We associate the human occupations with new geochronological data, and suggest the archaeological sites date to the wet periods of Marine Isotope Stage 5 and the Early Holocene. The archaeological sites indicate that humans repeatedly penetrated the ameliorated environments of the Rub’ al-Khali. The sites probably represent short-term occupations, with the Neolithic sites focused on hunting, as indicated by points and weaponry. Middle Palaeolithic assemblages at Mundafan support a lacustrine adaptive focus in Arabia. Provenancing of obsidian artifacts indicates that Neolithic groups at Mundafan had a wide wandering range, with transport of artifacts from distant sources.

Link

Nubian complex site from central Arabia (Crassard & Hilbert 2013)

From the paper:

The palaeoclimatic record of Arabia indicates that three distinct wet phases occurred during MIS 5 [109]. The first of these wet phases occurred between 130 and 125 kya (MIS 5e) and precedes the presence of Nubian technology in Arabia. The two following wet phases, positioned around 100 kya (MIS 5c) and between 80 to 75 kya (MIS 5a) may be viewed as possible windows for the Nubian expansion into and across Arabia (Figure 11).

PLoS ONE 8(7): e69221. doi:10.1371/journal.pone.0069221

A Nubian Complex Site from Central Arabia: Implications for Levallois Taxonomy and Human Dispersals during the Upper Pleistocene

Rémy Crassard, Yamandú Hieronymus Hilbert

Archaeological survey undertaken in central Saudi Arabia has revealed 29 surface sites attributed to the Arabian Middle Paleolithic based on the presence of Levallois blank production methods. Technological analyses on cores retrieved from Al-Kharj 22 have revealed specific reduction modalities used to produce flakes with predetermined shapes. The identified modalities, which are anchored within the greater Levallois concept of core convexity preparation and exploitation, correspond with those utilized during the Middle Stone Age Nubian Complex of northeast Africa and southern Arabia. The discovery of Nubian technology at the Al-Kharj 22 site represents the first appearance of this blank production method in central Arabia. Here we demonstrate how a rigorous use of technological and taxonomic analysis may enable intra-regional comparisons across the Arabian Peninsula. The discovery of Al-Kharj 22 increases the complexity of the Arabian Middle Paleolithic archaeological record and suggests new dynamics of population movements between the southern and central regions of the Peninsula. This study also addresses the dichotomy within Nubian core typology (Types 1 and 2), which was originally defined for African assemblages.

Link

81-100 thousand year old modern humans from China

From the paper:

The presumption of a late appearance of AMH in eastern Asia has been largely prompted by a remarkable yet dubious ‘gap’ between 100 and 40 ka ago lacking any human fossils, specifically between the latest archaic H. sapiens (i.e., Xujiayao, 104–125 ka and Maba, 129–135 ka) and the earliest modern H. sapiens (i.e., Ziyang, 35-40 ka) (data pooled from Wu and Poirier, 1995). In addition, genetic studies of present-day Chinese populations have supported the late appearance of AMH in eastern Asia (e.g., Chu et al., 1998). From this perspective, the AMH fossils from Tianyuan Cave at Zhoukoudian in northern China, dated to 39-42 ka B.P. (Before Present), have been readily accepted as the earliest representatives of modern H. sapiens in China, and the earliest evidence for the influx of African genes into the indigenous population (e.g., Shang et al., 2007; Cartmill and Smith, 2009; Endicott et al., 2009). 

However, the credibility of this supposed ~60 ka gap in the hominin fossil record and a late appearance of modern humans in China might have been compromised by the exclusion of a number of hominin fossils claimed to represent AMH from various limestone caves in southern China with more ancient dates, including Liujiang (between 68 and 153 ka, and most probably between 111 and 139 ka, Shen et al., 2002b), Ganqian (94–220 ka, Shen et al., 2002a), Bailiandong (>160 ka, Shen et al., 2001b), and Zhirendong (>100 ka, Liu et al., 2010a) in Guangxi. Based on our work on the sites of H. erectus and of both archaic and modern H. sapiens over the past twenty plus years, we argue that the temporal framework in China has been artificially ‘compressed and gapped,’ meaning that due to limitations in previous dating techniques and practices, the ages of Chinese hominin fossils have been significantly postdated (compressed), and that a temporal gap between archaic H. sapiens and AMH has been artificially created (gapped). To this scenario of the possible early presence of modern humans in China, here we report evidence from Huanglong Cave, a recently discovered Late Pleistocene hominin fossil- and stone artifact-bearing site, and discuss its impact on the mode of recent human evolution in eastern Asia.

I guess a lot depends on whether these teeth are accepted as belonging to AMH; if this holds, the early range of AMH must need to be extended even further east.

Such early dates are often seen as conflicting with the molecular clock (e.g., West and East Eurasians don't appear to have diverged ~100 thousand years ago no matter what assumptions about mutation rate one makes). But, we should not forget that divergence times can be suppressed either due to (i) admixture between the divergent populations, or (ii) due to an expansion of a highly successful population.


Journal of Human Evolution doi:10.1016/j.jhevol.2013.05.002

Mass spectrometric U-series dating of Huanglong Cave in Hubei Province, central China: Evidence for early presence of modern humans in eastern Asia

Guanjun Shen et al.

Most researchers believe that anatomically modern humans (AMH) first appeared in Africa 160-190 ka ago, and would not have reached eastern Asia until ∼50 ka ago. However, the credibility of these scenarios might have been compromised by a largely inaccurate and compressed chronological framework previously established for hominin fossils found in China. Recently there has been a growing body of evidence indicating the possible presence of AMH in eastern Asia ca. 100 ka ago or even earlier. Here we report high-precision mass spectrometric U-series dating of intercalated flowstone samples from Huanglong Cave, a recently discovered Late Pleistocene hominin site in northern Hubei Province, central China. Systematic excavations there have led to the in situ discovery of seven hominin teeth and dozens of stone and bone artifacts. The U-series dates on localized thin flowstone formations bracket the hominin specimens between 81 and 101 ka, currently the most narrow time span for all AMH beyond 45 ka in China, if the assignment of the hominin teeth to modern Homo sapiens holds. Alternatively this study provides further evidence for the early presence of an AMH morphology in China, through either independent evolution of local archaic populations or their assimilation with incoming AMH. Along with recent dating results for hominin samples from Homo erectus to AMH, a new extended and continuous timeline for Chinese hominin fossils is taking shape, which warrants a reconstruction of human evolution, especially the origins of modern humans in eastern Asia.

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A Middle Paleolithic link between North Africa and the Thar desert

One more piece of evidence against the idea that modern humans expanded Out-of-Africa because of the technological/behavioral revolution evidenced during the Upper Paleolithic/Late Stone Age.

And, one more piece of evidence against the idea that early modern humans in Eurasia died out and were replaced wholesale circa 50-60 thousand years ago from a fresh OoA impulse. It would have been possible to suppose such a thing if the evidence for MP African influence was minor or geographically localized, but much more difficult when it extends over a wide region.

Of course, the attribution of the Katoati assemblages to modern humans is done indirectly by linking them to MSA sites of the Sahara, but the proliferation of real archaeological sites (see map) that can be linked to OoA makes it difficult to adopt the idea of an archaeologically invisible late OoA that (somehow) replaced all previous inhabitants.

Quaternary Science Reviews Available online 5 July 2013

Middle Palaeolithic occupation in the Thar Desert during the Upper Pleistocene: the signature of a modern human exit out of Africa?

James Blinkhorn et al.

The Thar Desert marks the transition from the Saharo-Arabian deserts to the Oriental biogeographical zone and is therefore an important location in understanding hominin occupation and dispersal during the Upper Pleistocene. Here, we report the discovery of stratified Middle Palaeolithic assemblages at Katoati in the north-eastern Thar Desert, dating to Marine Isotope Stages (MIS) 5 and the MIS 4–3 boundary, during periods of enhanced humidity. Hominins procured cobbles from gravels at the site as evidenced by early stages of stone tool reduction, with a component of more formalised point production. The MIS 5c assemblages at Katoati represent the earliest securely dated Middle Palaeolithic occupation of South Asia. Distinctive artefacts identified in both MIS 5 and MIS 4–3 boundary horizons match technological entities observed in Middle Palaeolithic assemblages in South Asia, Arabia and Middle Stone Age sites in the Sahara. The evidence from Katoati is consistent with arguments for the dispersal of Homo sapiens populations from Africa across southern Asia using Middle Palaeolithic technologies.

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Continuity of microblade technology in India since 45ka

An interesting new paper extends continuity of microblade technologies in India to ~45ka, and hence makes it probable that these were introduced by AMH together with the UP colonization of the rest of Eurasia.

I am not sure that the authors' suggestion that early modern humans were "tropically adapted" is certain. Personally, my idea du jour is to derive them from the Saharo-Arabian belt. In any case, as an advocate of "early OOA" (in the sense of pre-UP/LSA), it makes sense to me that modern humans in Eurasia would be initially climate-limited and at a disadvantage vis a vis archaic Eurasians inhabiting regions for which they were maladapted. In my opinion, it was the technological revolution of ~50ka being responsible for the extension of their range at the expense of other Eurasians.

PLoS ONE 8(7): e69280. doi:10.1371/journal.pone.0069280

Continuity of Microblade Technology in the Indian Subcontinent Since 45 ka: Implications for the Dispersal of Modern Humans

Sheila Mishra et al.

We extend the continuity of microblade technology in the Indian Subcontinent to 45 ka, on the basis of optical dating of microblade assemblages from the site of Mehtakheri, (22° 13' 44″ N Lat 76° 01' 36″ E Long) in Madhya Pradesh, India. Microblade technology in the Indian Subcontinent is continuously present from its first appearance until the Iron Age (~3 ka), making its association with modern humans undisputed. It has been suggested that microblade technology in the Indian Subcontinent was developed locally by modern humans after 35 ka. The dates reported here from Mehtakheri show this inference to be untenable and suggest alternatively that this technology arrived in the Indian Subcontinent with the earliest modern humans. It also shows that modern humans in Indian Subcontinent and SE Asia were associated with differing technologies and this calls into question the “southern dispersal” route of modern humans from Africa through India to SE Asia and then to Australia. We suggest that modern humans dispersed from Africa in two stages coinciding with the warmer interglacial conditions of MIS 5 and MIS 3. Competitive interactions between African modern humans and Indian archaics who shared an adaptation to tropical environments differed from that between modern humans and archaics like Neanderthals and Denisovans, who were adapted to temperate environments. Thus, while modern humans expanded into temperate regions during warmer climates, their expansion into tropical regions, like the Indian Subcontinent, in competition with similarly adapted populations, occurred during arid climates. Thus modern humans probably entered the Indian Subcontinent during the arid climate of MIS 4 coinciding with their disappearance from the Middle East and Northern Africa. The out of phase expansion of modern humans into tropical versus temperate regions has been one of the factors affecting the dispersal of modern humans from Africa during the period 200–40 ka.

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Analysis of multi-merge dataset of human autosomal microsatellite variation

Microsatellites may be a little "retro" in the age of million-SNP arrays and whole genome sequencing, but one has to admit that the following figure, resulting from a merge of multiple microsatellite datasets, is pretty impressive.

G3: Genes|Genomes|Genetics doi: 10.1534/g3.113.005728

Population Structure in a Comprehensive Genomic Data Set on Human Microsatellite Variation

Trevor J. Pemberton et al.

Over the past two decades, microsatellite genotypes have provided the data for landmark studies of human population-genetic variation. However, the various microsatellite data sets have been prepared with different procedures and sets of markers, so that it has been difficult to synthesize available data for a comprehensive analysis. Here, we combine eight human population-genetic data sets at the 645 microsatellite loci they share in common, accounting for procedural differences in the production of the different data sets, to assemble a single data set containing 5,795 individuals from 267 worldwide populations. We perform a systematic analysis of genetic relatedness, detecting 240 intra-population and 92 inter-population pairs of previously unidentified close relatives and proposing standardized subsets of unrelated individuals for use in future studies. We then augment the human data with a data set of 84 chimpanzees at the 246 loci they share in common with the human samples. Multidimensional scaling and neighbor-joining analyses of these data sets offer new insights into the structure of human populations and enable a comparison of genetic variation patterns in chimpanzees with those in humans. Our combined data sets are the largest of their kind reported to date and provide a resource for use in human population-genetic studies.

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~60-50 thousand coastal migration to Asia from Africa affirmed

My own opinions on this matter have been repeated ad nauseam in this blog, so I will only briefly touch on a couple of points in this new article.

Contrary to the authors' claim that: "The size of the mtDNA database is very substantial: currently there are almost 13,000 complete non-African mtDNA genomes available, not one of which is pre-L3." there are plenty of pre-L3 mtDNA in Eurasia. Some (or indeed most?) of these might represent more recent African admixture, and one could argue why they believe that to be the case, but no one has ever studied pre-L3 Eurasian mtDNA to conclude that none of it had an ancient presence in Eurasia. The native non-existence of pre-L3 in Eurasia is a viewpoint, not a fact.

Second, the authors present the following table:

Note, however, that they have chosen to date the common ancestor of all African sublineages (to ~70.2ky using ML method), but they have not done the same for the common ancestor of all non-African sublineages (i.e., M+N). A recent study estimates M+N to be 77KBP and L3 to be 78.3KBP, with other possibilities depending on method and portion of the molecule examined.

At present, I see no good reason to think that haplogroup L3 originated either in Africa or Eurasia; one could argue for an African origin, but temporal priority for African L3 is not established. The only thing that seems to be established is that there are "more" L3 subclades in Africa, which is phylogenetically meaningless until the bifurcating structure of the L3 subtree is resolved. And, we should also not forget that the Toba eruption did not cause a volcanic winter in Africa, nor was Africa affected by the drying up of the Sahara-Arabia belt c. 70kya, both of which may have suppressed Eurasian mtDNA variation within L3, irrespective of its ultimate origins. And, as I've argued before, both Toba and the post-70kya ecological crisis are excellent candidates for a Eurasian bottleneck caused by pre-existing populations surviving in refugia such as this.

Finally, the authors dismiss the possibility of an overestimated autosomal mutation rate and its implications for human history: "Recent reestimates of the autosomal mutation rate from whole-genome pedigree data suggest a European–Asian split time of 40–80 ka, although they do not, as has been suggested, lend any support to a dispersal fromAfrica before 80 ka (36) (Genetics)." 

Actually, the most recent estimate might be consistent with a ~96ky split of Africans from non-Africans, and the mutation rate issue is material to the timing of the African/non-African split. It's not clear where the needle will settle when the issue is resolved, but there's plenty of room for both pre- and post-Toba Out-of-Africa as things stand.


PNAS doi: 10.1073/pnas.1306043110

Genetic and archaeological perspectives on the initial modern human colonization of southern Asia

Paul Mellars et al.

It has been argued recently that the initial dispersal of anatomically modern humans from Africa to southern Asia occurred before the volcanic “supereruption” of the Mount Toba volcano (Sumatra) at ∼74,000 y before present (B.P.)—possibly as early as 120,000 y B.P. We show here that this “pre-Toba” dispersal model is in serious conflict with both the most recent genetic evidence from both Africa and Asia and the archaeological evidence from South Asian sites. We present an alternative model based on a combination of genetic analyses and recent archaeological evidence from South Asia and Africa. These data support a coastally oriented dispersal of modern humans from eastern Africa to southern Asia ∼60–50 thousand years ago (ka). This was associated with distinctively African microlithic and “backed-segment” technologies analogous to the African “Howiesons Poort” and related technologies, together with a range of distinctively “modern” cultural and symbolic features (highly shaped bone tools, personal ornaments, abstract artistic motifs, microblade technology, etc.), similar to those that accompanied the replacement of “archaic” Neanderthal by anatomically modern human populations in other regions of western Eurasia at a broadly similar date.

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Demographic history from distribution of shared IBS lengths

An interesting new paper has appeared in PLoS Genetics, with what appears to be a nice new method for inferring demographic history from genome-scale data. The authors observe that segments inherited from common ancestors are "broken up" by mutation as time goes by: initially there are long identical tracts, but these are "split" whenever a new mutation appears, so they study the distribution of lengths of the pieces between mutations that remain identical by state.

A practical application of the new technique is applied to European-African history:

We estimate that the European-African divergence occurred 55 kya and that gene flow continued until 13 kya. About 5.8% of European genetic material is derived from a ghost population that diverged 420 kya from the ancestors of modern humans. The out-of-Africa bottleneck period, where the European effective population size is only 1,530, lasts until 5.9 kya.

The authors use the "old" 2.5x10-8 mutation derived from a paleontological calibration of the human-chimp split, which renders their calculations comparable to many past papers on human demographic history, but at odds with many of the newer rates that are approximately twice slower. There is lingering controversy about the appropriateness of different rates.

The authors estimate that perhaps a 1.75x increase in their estimates will be effected if the slower rates are used; this is not 2x as one might expect from a 2x slower rate, because their age estimates depend on both the mutation rate (for which there is controversy) and the recombination rate. By applying the 1.75x correction factor, we may obtain a time for European-African split at 96 thousand years and a continuation of gene flow between Europeans and Africans down to 23 thousand years.

I suppose that things might be complicated by the occurrence of Amerindian-like admixture in some West Eurasians in the past, as well as the occurrence of intra-African admixture (which I've called "Palaeoafrican") in the ancestry of Yoruba, both of which do not appear to be modeled here: the former might have infused an "African-less" component of ancestry at a time when the authors suggest that there was continuing gene flow between West Eurasia and African; the latter would inflate the effective population size of the Yoruba and make the appear earlier diverged from non-Africans.

In any case, this is a useful addition to our understanding of human history and may tie in to some of my arguments about Eurasian back-migration into Africa (although the authors consider bidrectional gene flow in their model). The lack of non-M,N mitochondria in non-Africans makes the post-OoA gene flow from Africa->Eurasia difficult to stomach, while the opposing migration of Y-haplogroup E bearers into Africa (as I have suggested) seems too instantaneous to account for the authors' evidence for protracted gene flow.


PLoS Genet 9(6): e1003521. doi:10.1371/journal.pgen.1003521

Inferring Demographic History from a Spectrum of Shared Haplotype Lengths

Kelley Harris, Rasmus Nielsen

There has been much recent excitement about the use of genetics to elucidate ancestral history and demography. Whole genome data from humans and other species are revealing complex stories of divergence and admixture that were left undiscovered by previous smaller data sets. A central challenge is to estimate the timing of past admixture and divergence events, for example the time at which Neanderthals exchanged genetic material with humans and the time at which modern humans left Africa. Here, we present a method for using sequence data to jointly estimate the timing and magnitude of past admixture events, along with population divergence times and changes in effective population size. We infer demography from a collection of pairwise sequence alignments by summarizing their length distribution of tracts of identity by state (IBS) and maximizing an analytic composite likelihood derived from a Markovian coalescent approximation. Recent gene flow between populations leaves behind long tracts of identity by descent (IBD), and these tracts give our method power by influencing the distribution of shared IBS tracts. In simulated data, we accurately infer the timing and strength of admixture events, population size changes, and divergence times over a variety of ancient and recent time scales. Using the same technique, we analyze deeply sequenced trio parents from the 1000 Genomes project. The data show evidence of extensive gene flow between Africa and Europe after the time of divergence as well as substructure and gene flow among ancestral hominids. In particular, we infer that recent African-European gene flow and ancient ghost admixture into Europe are both necessary to explain the spectrum of IBS sharing in the trios, rejecting simpler models that contain less population structure.

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