SMBE 2014 Ancient Genomics

Some interesting titles from the upcoming SMBE 2014 conference:

O-11	Genotyping of 390,000 SNPs in more than forty 3,000-9,000 year old humans from the ancient Russian steppe David Reich*1,2, Nadin Rohland1,2, Swapan Mallick1,2, Iosif Lazaridis1, Eadaoin Harney1, Susanne Nordenfelt1, Qiaomei Fu3, Matthias Meyer3, Dorcas Brown4, David Anthony4, Nick Patterson2 1Harvard Medical School, USA, 2Broad Institute of Harvard and MIT, USA, 3Max Planck Institute for Evolutionary Anthropology, Germany, 4Hartwick College, USA
O-12	Statistical Inference of Archaic Introgression In Central African Pygmies PingHsun Hsieh*1, Jeffrey Wall2, Joseph Lachance3, Sarah Tishkoff3, Ryan Gutenkunst1, Michael Hammer1 1University of Arizona, USA, 2University of California, USA, 3University of Pennsylvania, USA
O-13	Patterns of ancient selection in modern humans around candidate sites Fernando Racimo*1,2, Martin Kuhlwilm2, Montgomery Slatkin1 1University of California - Berkeley, USA, 2Max Planck Institute for Evolutionary Anthropology, Germany
O-14	Ancient maize from the American Southwest Rute R da Fonseca*1, Bruce Smith2, Nathan Wales1, Enrico Cappellini1, Matteo Fumagalli3, Pontus Skoglund4, Anders Albrechtsen1, Jeff Ross-Ibarra5, Tom Gilbert1 1Copenhagen University, Denmark, 2Smithsonian Institution, USA, 3UC Berkeley, USA, 4Uppsala University, Sweden,5UC Davis, USA
O-15	The complete genome sequence of a 45,000-year-oldmodern human from Eurasia Qiaomei Fu*1,2, Bence Viola1,3, Heng Li5,6, Priya Moorjani6, Flora Jay4, Aximu Ayinuer-Petri1, Susan Keates8, Yaroslav V. Kuzmin7, Montgomery Slatkin4, David Reich5,6, Janet Kelso1, Svante Pääbo1 1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Germany, 2Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, China, 3Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Germany, 4Department of Integrative Biology, University of California, USA, 5Broad Institute of MIT and Harvard, Cambridge, USA, 6Department of Genetics,Harvard Medical School, USA, 7Institute of Geology & Mineralogy, Siberian Branch of the Russian Academy of Sciences, Russia,8University Village, USA

The whole program appears to be online, so feel free to point to any noteworthy abstracts in the comments.

SMBE 2013 abstracts

Some abstracts from the SMBE 2013 conference that will take place next week. 

Legacy of Early Migrants in Neolithic East Asian Hunter-Gatherer from Fukushima, Japan

K.K. Hideaki et al.   

Clarifying the genetic relationship between Neolithic East Asian Hunter-Gatherer, Jomon people, and modern human populations is one of the Keystones to understand the controversial history of modern East Asian populations. Jomon people inhabited in the Japanese archipelago from 16,000 years ago, and their origin and the relationship with modern humans have been debated for a long time. To solve these questions, we obtained 20 million base pairs of genomic DNA from a ~4,000-year-old Jomon male tooth, excavated in Sanganji shell mound, Fukushima, Japan. We compared his genetic components with the data of modern worldwide populations. Our major findings are: (1) Sanganji Jomon was very similar with modern East Asians when we compared the worldwide populations in the PCA plot; (2) when only East Asians were compared, Sanganji Jomon was distant from both modern Northeast and Southeast Asians, indicating that Sanganji Jomon people were already isolated from other continental populations for a long time; (3) the Sanganji Jomon male shared more SNP alleles with southern and northern minorities in China than geographically close Han Chinese, implying a complex history of people in China after the divergence between Jomon ancestors and Eurasian continent people; (4) Sanganji Jomon is genetically closer to modern mainland Japanese than continental populations, indicating that some of their components were transmitted to modern Japanese; (5) within Japanese archipelago, Ainu and Ryukyuan (the populations of northern and southern edges of the Japanese archipelago) have more Jomon components than mainland Japanese, indicating that the genetic effect of agricultural people who migrated from the Eurasian continent in and after the Yayoi period is stronger in Mainland Japanese than Ainu and Ryukyuan.

Extensive Gene Gain in Human Brain Evolution

Yong E. Zhang et al.
The genetic changes contributing to the evolution of the human brain have always attracted wide interest. A emerging consensus view is that while there have been no major patterns of genome-wide changes to the coding regions of brain-related genes, cis-regulatory changes of these genes have played a key role. Here, motivated by anecdotal studies of primate-specific genes implicated in brain function, we identified thousands of lineage-specific (primate-specific or rodent-specific) genes by mining syntenic vertebrate genomic alignments and examined the expression profile of these genes in both fetal and adult brains of human and mouse across different transcriptome profiling platforms. We found that an excess of lineage-specific genes are expressed in the early (fetal or infant) developing human brain compared with those in mouse brain. Expression data covering numerous subregions of the developing brain further demonstrate that these young genes are mainly transcribed in the neocortex. They originated in the evolutionary period during which the neocortex was expanding, suggesting the functional association of new genes with this newly evolving brain structure. Our data reveal that evolutionary change in the development of the human brain happened at the protein level by gene origination and also via evolution of regulatory networks, as hinted by the enrichment of primate-specific transcriptional regulators in our dataset. More than that, these ?ndings suggest that genomes are continually evolving in both sequence and content, eroding the conservation endowed by common ancestry. Despite increasing recognition of the importance of new genes, these genes are still seriously under-characterized in functional studies and that new gene annotation is inconsistent in current practice. We propose an integrative approach based on functional and evolutionary genomic methods to better annotate these non-conserved genes.

Recent Human Demography Impacts the Architecture of Genetic Disease in Populations but Not Individual Genetic Load

Yuval Simons et al.
Human populations have undergone dramatic changes in population sizes in the past 100,000 years, including a severe bottleneck of non-African populations and recent explosive population growth. There is currently great interest in how these demographic events may have affected the burden of deleterious mutations in individuals and the allele frequency spectrum of disease mutations in populations. Here we use population genetic models to show that--contrary to previous conjectures--recent human demography likely had very little impact on the average burden of deleterious mutations carried by individuals. This prediction is supported by exome sequence data showing that African American and European American individuals carry very similar burdens of damaging mutations. We next considered whether recent population growth has increased the importance of very rare mutations in disease. Our analysis predicts that, even given recent growth, it is unlikely that very rare mutations contribute a large fraction of disease heritability except for diseases that are largely due to strongly deleterious mutations. In summary, demographic history has dramatically impacted patterns of variation in different human populations, but these changes likely had little impact on either genetic load or on the importance of rare variants in most complex traits.

Functional and Population Genetic Analyses of a High-Coverage Neandertal Genome

Fernando Racimo et al.
We have sequenced the genome of a Neandertal from the Altai mountains in Siberia at 50-fold coverage. This Neandertal was located in the same cave as the Denisovan individual, but is phylogenetically closer to Neandertals from Western Eurasia. To avoid confusion, we call this individual the Altai Neandertal. Here we show an assessment of genome data quality and functional and population genetic comparisons with the Denisovan genome and a set of 25 high-coverage modern human genomes. We present an analysis of genes with recent changes in either the modern human lineage or the archaic human lineage (Neandertal+Denisova). We find enrichment for nonsynonymous changes in genes associated with melanosomes in the modern human lineage, and genes associated with particular muscoskeletal morphologies in the archaic human lineage. We utilize a compound deleteriousness scoring that allows us to combine a variety of conservation, regulatory and expression data to rank all modern and archaic-specific single-nucleotide changes and InDels across the genome, and predict which are those that could have been most disruptive in our evolutionary history. Furthermore, we overlap the modern-specific catalog with the top regions of a screen for selective sweeps exclusive to the modern human lineage, and observe enrichments for changes in genes related to ion channel activity, muscle contraction and membrane transport. Finally, we note an excess of ancestral alleles in the Denisovan individual relative to the Altai Neandertal individual, which is strongest at sites where modern humans are fixed derived. We develop an approximate Bayesian computation approach that allows us to test different models, and conclude that gene flow between the Denisovan individual and a more anciently diverged human lineage is most consistent with the patterns observed.

Multiple Episodes of Population Mixture in Southern African History

Joseph K. Pickrell et al.
The history of southern Africa involved interactions between indigenous hunter-gatherers and a range of populations that moved temporarily or permanently into the region. The influence of these interactions on the genetic structure of current populations remains unclear. Here, using patterns of linkage disequilibrium, we show that there are at least two admixture events in the genetic history of southern African hunter-gatherers and pastoralists: one involving populations related to Niger-Congo-speaking African populations, and one which introduced ancestry most closely related to west Eurasian (European or Middle Eastern) populations. We estimate that at least a few percent of ancestry in the Khoisan is derived from this latter admixture event, which occurred on average 1,200-1,800 years ago. We show that a similar signal of west Eurasian ancestry is present throughout eastern Africa; in particular, we also find evidence for two admixture events in the genetic history of several Kenyan, Tanzanian, and Somali populations, the earliest of which involved populations related to southern Europeans and which we date to approximately 2700 - 3300 years ago. We thus suggest that west Eurasian ancestry entered southern Africa indirectly through eastern Africa. These results demonstrate how large-scale genomic datasets can inform complex models of population movements, and highlight the genomic impact of largely uncharacterized back-to-Africa migrations in human history.

Mechanistic Models of Admixture and Approximate-Approximate-Bayesian Computation 

Noah Rosenberg et al.   

Investigations of the history of migrations that underlie admixed populations often use nonmechanistic admixture models rather than a modeling perspective that incorporates a population-genetic history of admixture built from first principles. We build a general model of admixture that mechanistically accounts for complex admixture processes, considering two source populations that contribute to the ancestry of a hybrid population, potentially with variable contributions across generations. For a random individual in the hybrid population at a given point in time, we study the fraction of admixture originating from a specific one of the source populations. Quite different admixture processes can produce identical mean admixture across individuals, but such processes typically produce different values for the variance of admixture. Interestingly, even without considering sex chromosomes, the variance of admixture for autosomes captures information about sex-specific migration in the contributions of the source populations to the admixed group. To perform inference under the model, we use approximate-approximate-Bayesian computation (AABC), a modification of approximateBayesian computation well-suited to estimation under complex mechanistic models that are computationally intensive to simulate. The model and inference method can contribute to an understanding of the theory and analysis of the history of admixed populations.

Inferring Human Population History and Migration Patterns from Multiple Genome Sequences

Stephan Schiffels, Richard Durbin
The availability of human genomes from populations across the world has given rise to new inference methods that exploit high-coverage sequence data. Among the most influential recent developments is the Pairwise Sequentially Markovian Coalescenct (PSMC) by Li and Durbin, 2011. While PSMC infers the demographic history for times between 20kya and 2mya with high resolution, neither the more recent evolutionary history nor migration patterns across populations can be adressed. Here we present a new method that overcomes both of these shortcomings. The Multiple Sequentially Markovian Coalescent (MSMC) infers the recent evolutionary history within and across populations only a few thousand years ago and younger. MSMC models the pattern of mutations in multiple genome sequences under the coalescent with recombination. It fits local genealogical trees to the observed pattern, focussing on the first coalescence among any two individuals. We apply our method to the genome sequences from several family trios from the 1000 Genomes project with African, European, Asian and SouthAmerican ancestry. We infer population sizes and migration rates as a function of time with high resolution. In particular, our method resolves the more recent evolutionary history of non-African populations after the out-of-Africa event, such as the peopling of the Americas.

SMBE 2012 abstracts (Part II)

Some more abstracts from SMBE 2012.

The Neolithic trace in mitochondrial haplogroup U8 

Joana Barbosa Pereira 1,2 , Marta Daniela Costa 1,2 , Pedro Soares 2 , Luísa Pereira 2,3 , Martin Brian Richards 1,4 1 Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK, 2 Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal,  3 Faculdade de Medicina da  Universidade do Porto, Porto, Portugal,  4 School of Applied Sciences, University of Huddersfield, Huddersfield, UK  

The mitochondrial DNA (mtDNA) still remains an important marker in the study of human history, especially if  considering the increasing amount of data available. Among the several questions regarding human history that are  under debate, the model of expansion of agriculture into Europe from its source in the Near East is still unclear. Recent  studies have indicated that clusters belonging to haplogroup K, a major clade from U8, might be related with the  Neolithic expansions. Therefore, it is crucial to identify the founder lineages of the Neolithic in Europe so that we may  understand the real genetic input of the first Near Eastern farmers in the current European population and comprehend  how agriculture spread so quickly throughout all Europe.  In order to achieve this goal, a total of 55 U8 samples from the Near East, Europe and North Africa were selected for  complete characterisation of mtDNA. A maximum-parsimonious phylogenetic tree was constructed using all published  sequences available so far. Coalescence ages of specific clades were estimated using ρ statistic, maximum likelihood  and Bayesian methods considering a mutation rate for the complete molecule corrected for purifying selection.   Our results show that U8 dates to ~37-54 thousand years ago (ka) suggesting that this haplogroup might have been  carried by the first modern humans to arrive in Europe, ~50 ka. Haplogroup K most likely originated in the Near East  ~23-32 ka where it might have remained during the Last Glacial Maximum, between 26-19 years ago. The majority of K  subclades date to the Late Glacial and are related with the repopulation of Europe from the southern refugia areas. Only  a few lineages appear to reflect post glacial, Neolithic or post-Neolithic expansions, mostly occurring within Europe. The  major part of the lineages dating to the Neolithic period seems to have an European origin with exception of haplogroup  K1a4 and K1a3. Clade K1a4 appears to be originated from the Near East where it also reaches its highest peak of  diversity. Despite the main clades of K1a4 arose in the Near East during the Late Glacial, its subclade K1a4a1 dates to  ~9-11 ka and is most likely related with the Neolithic dispersal to Europe. Similarly, K1a3 probably originated in the Near  East during the Late Glacial and its subclade K1a1a dispersed into Europe ~11-13 ka alongside with the expansion of  agriculture. 

Late Glacial Expansions in Europe revealed through the fine-resolution characterisation of mtDNA haplogroup  U8 

Marta Daniela Costa 1,2 , Joana Barbosa Pereira 1,2 , Pedro Soares 2 , Luisa Pereira 2,3 , Martin Brian Richards 1,4 1 Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK, 2 IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal,  3 Faculdade de  Medicina, Universidade do Porto, Porto, Portugal,  4 School of Applied Sciences, University of Huddersfield, Huddersfield,  UK  

The maternally inherited and fast evolving mitochondrial DNA (mtDNA) molecule is a highly informative tool with which  to reconstruct human prehistory. This has become even more true in recent years, as mtDNA based studies are  becoming more robust and powerful due to the availability of complete mtDNA genomes. These allow better mutation  rate estimates and fine-resolution characterisation of the phylogeography of mtDNA haplogroups, or named  clades.  MtDNA haplogroup K, the major subclade of U8, occurs at low frequencies through West Eurasian populations,  and is much more common in Ashkenazi Jews. However, the lack of variation on the first hypervariable segment (HVSI) has precluded any meaningful phylogeographic analysis to date. We therefore completely sequenced 50 haplogroup  K and 5 non-K U8 mtDNA samples from across Europe and the Near East, and combined them with 343 genomes  previously deposited in GenBank, in order to reconstruct a detailed phylogenetic tree. By combining several inference  methods, including maximum parsimony, maximum likelihood and Bayesian inference it was possible to trace the  timescale and geography of the main expansions and dispersals associated with this lineage. We confirmed that  haplogroup K, dating to ~32 thousand years (ka) ago, descended from the U8 clade, which coalesces ~48 ka ago. The  latter is close to the timing of the first arrival of modern humans in Europe and U8 could be one of the few surviving  mtDNA lineages brought by the first settlers from the Near East. U8 split into the widespread U8b, at ~43 ka, and U8a,  which seems to have expanded only in Europe ~24 ka ago. Considering the pattern of diversity and the geographic  distribution, haplogroup K is most likely to have arisen in the Near East, ~32 ka ago. However, some subclades were  evidently carried to Europe during the Last Glacial Maximum (LGM). We observed significant expansions of haplogroup  K lineages in the Late Glacial period (14-19 ka), reflecting expansions out of refuge areas in southwest and possibly  also southeast Europe. 

Reticulated origin of domesticated tetraploid wheat 

Peter Civan Centro de Ciencias do Mar, Universidade do Algarve, Faro, Portugal  

The past 15 years have witnessed a notable scientific interest in the topic of crop domestication and the emergence of  agriculture in the Near East. Multi-disciplinary approaches brought a significant amount of new data and a multitude of  hypotheses and interpretations. However, some seemingly conflicting evidence, especially in the case of emmer wheat,  caused certain controversy and a broad scientific consensus on the circumstances of the wheat domestication has not  been reached, yet.  The past phylogenetic research has translated the issue of wheat domestication into somewhat simplistic mono- /polyphyletic dilemma, where the monophyletic origin of a crop signalizes rapid and geographically localized  domestication, while the polyphyletic evidence suggests independent, geographically separated domestication events.  Interestingly, the genome-wide and haplotypic data analyzed in several studies did not yield consistent results and the  proposed scenarios are usually in conflict with the archaeological evidence of lengthy domestication.  Here I suggest that the main cause of the above mentioned inconsistencies might lie in the inadequacy of the divergent,  tree-like evolutional model. The inconsistent phylogenetic results and implicit archaeological evidence indicate a  reticulate (rather than divergent) origin of domesticated emmer. Reticulated genealogy cannot be properly represented  on a phylogenetic tree; hence different sets of samples and genetic loci are prone to conclude different domestication  scenarios. On a genome-wide super-tree, the conflicting phylogenetic signals are suppressed and the origin of  domesticated crop may appear monophyletic, leading to misinterpretations of the circumstances of the Neolithic  transition.  The network analysis of multi-locus sequence data available for tetraploid wheat clearly supports the reticulated origin of  domesticated emmer and durum wheat. The concept of reticulated genealogy of domesticated wheat sheds new light  onto the emergence of Near-Eastern agriculture and is in agreement with current archaeological evidence of protracted  and dispersed emmer domestication.

High-coverage population genomics of diverse African hunter-gatherers 

Joseph Lachance 1 , Benjamin Vernot 2 , Clara Elbers 1 , Bart Ferwerda 1 , Alain Froment 3 , Jean-Marie Bodo 4 , Godfrey  Lema 5 , Thomas Nyambo 5 , Timothy Rebbeck 1 , Kun Zhang 6 , Joshua Akey 2 , Sarah Tishkoff 1 1 University of Pennsylvania, Philadelphia, PA, USA,  2 University of Washington, Seattle, WA, USA,  3 IRD-MNHN, Musee  de l'Homme, Paris, France,  4 Ministere de la Recherche Scientifique et de l’Innovation, Yaounde, Cameroon,  5 Muhimbili  University College of Health Sciences, Dar es Salaam, Tanzania,  6 University of California at San Diego, San Diego, CA,  USA     

In addition to their distinctive subsistence patterns, African hunter-gatherers belong to some of the most genetically  diverse populations on Earth.  To infer demographic history and detect signatures of natural selection, we sequenced  the whole genomes of five individuals in each of three geographically and linguistically diverse African hunter-gatherer  populations at >60x coverage.  In these 15 genomes we identify 13.4 million variants, many of which are novel,  substantially increasing the set of known human variation.  These variants result in allele frequency distributions that are  free of SNP ascertainment bias.  This genetic data is used to infer population divergence times and demographic history  (including population bottlenecks and inbreeding).  We find that natural selection continues to shape the genomes of  hunter-gatherers, and that deleterious genetic variation is found at similar levels for hunter-gatherers and African  populations with agricultural or pastoral subsistence patterns.  In addition, the genomes of each hunter-gatherer  population contain unique signatures of local adaptation.  These highly-divergent genomic regions include genes  involved in immunity, metabolism, olfactory and taste perception, reproduction, and wound healing.

Reconstructing past Native American genetic diversity in Puerto Rico from contemporary populations Marina Muzzio 1,2 , Fouad Zakharia 1 , Karla Sandoval 1 , Jake K. Byrnes 3 , Andres Moreno-Estrada 1 , Simon Gravel 1 , Eimear  Kenny 1 , Juan L. Rodriguez-Flores 5 , Chris R. Gignoux 6 , Wilfried Guiblet 4 , Julie Dutil 7 , The 1000 Genomes Consortium 0 ,  Andres Ruiz-Linares 8 , David Reich 9,10 , Taras K. Oleksyk 4 , Juan Carlos Martinez-Cruzado 4 , Esteban Gonzalez  Burchard 6 , Carlos D. Bustamante 1 1 Department of Genetics, Stanford University School of Medicine, Stanford, California, USA,  2 Facultad de Ciencias  Naturales, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina,  3 Ancestry. com®, San Francisco,  California, USA,  4 Department of Biology, University of Puerto Rico at Mayagüez, Mayagüez, Puerto Rico,  5 Department  of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA,  6 Institute for Human Genetics,  University of California San Francisco, San Francisco, California, USA,  7 Ponce School of Medicine, Ponce, Puerto Rico, 8 Department of Genetics, Evolution and Environment. University College London, London, UK,  9 Department of  Genetics, Harvard Medical School, Boston, Massachusetts, USA,  10 Broad Institute of MIT and Harvard, Cambridge,  Massachusetts, USA  

The Caribbean region has a rich cultural and biological diversity, including several countries with different languages,  and important historical events like the arrival of the Europeans in the late fifteenth century affected it deeply. Although it  has been said that two main Native American groups peopled the Caribbean at the time of Columbus’s voyages—the  Arawakan-speaking Tainos and the Caribs—this model has been questioned because it comes from the descriptions  written by the conquerors. The archaeological record shows a richer picture of trade among the islands, cultural change  and diversity than what colonial documents depict, from the early settlements around 8000 B.P. to the chiefdoms and  towns at the time of contact. How this area was peopled and how its inhabitants interacted with the surrounding  continent are questions that remain to be answered due to the fragmentary nature of the historical and archaeological  records.   
We aim to reconstruct the Native American genetic diversity from the time of the Spanish arrival at the island of Puerto  Rico from its contemporary population. We seek to find out how the original peopling of Puerto Rico occurred, along  with which contemporary Native American populations are the most closely related to the Native tracks found. We used  PCAdmix to trace Native American segments in admixed individuals, thus enabling us to reconstruct the original native  lineages previous to the European and African contact.   

Specifically, we generated local ancestry calls for the 70 parents of the 35 complete Puerto Rican trios from the wholegenome and Illumina Omni 2.5M chip Genotype data of the 1000 Genomes Project, both to examine genome-wide  admixture patterns and to infer demographic historical events from ancestry tract length distributions and an ancestryspecific PCA approach, adding 55 Native American groups as potential source populations (N=475 genotyped through  Illumina’s 650K array) and 15 selected Mexican trios (genotyped on Affymetrix’s 6.0 array, including about 906,000  SNPs) to provide population context. ADMIXTURE analysis has shown that in Puerto Rico there is no single source of  contribution for the Native component. Rather, this component seems to include a mixture of major Mexican and  Andean components with little contributions from the Amazonian isolates. On the other hand, the ancestry-specific PCA  plotted the Puerto Rican Native segments tightly clustered with the Native segments of groups from the same language  family as the Tainos (Equatorial-Tucanoan), showing a clear association between linguistics and genetics instead of a  geographical one.

 Inference of demographic history and natural selection in African Pygmy populations from whole-genome  sequencing data

 Martin Sikora 1 , Etienne Patin 2 , Helio Costa 1 , Katherine Siddle 2 , Brenna M Henn 1 , Jeffrey M Kidd 1,3 , Ryosuke Kita 1 ,  Carlos D Bustamante 1 , Lluis Quintana-Murci 2 1 Department of Genetics, School of Medicine, Stanford Uni, Stanford, CA, USA,  2 Unit of Human Evolutionary Genetics,  Institut Pasteur, CNRS URA3012, Paris, France,  3 Departments of Human Genetics and Computational Medicine and  Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA     

The Pygmy populations of Central Africa are some of the last remaining hunter-gatherers among present-day human  populations, and can be broadly classified into two geographically separated groups, the Western and Eastern Pygmies.  Compared to their neighboring populations of predominantly Bantu origin, Pygmy populations show distinct cultural and  physical characteristics, most notably short stature, often referred to as the “Pygmy phenotype”. Given their distinct  physical characteristics, the questions of the demographic history and origin of the Pygmy phenotype have attracted  much attention. Previous studies have shown an ancient divergence (~60,000 years ago) of the ancestors of modernday Pygmies from non-Pygmies, and a more recent split of the Eastern and Western Pygmy groups. However, these  studies were generally based on a relatively small set of markers, precluding accurate estimations of demographic  parameters. Furthermore, despite the considerable interest, to date there is still little known about the genetic basis of  the small stature phenotype of Pygmy populations.   

In order to address these questions, we sequenced the genomes of 47 individuals from three populations: 20 Baka, a  Pygmy hunter-gatherer population from the Western subgroup of the African Pygmies; 20 Nzebi, a neighboring nonPygmy agriculturist population from the Bantu ethnolinguistic group; as well as 7 Mbuti, Eastern Pygmy population, from  the Human Genome Diversity Project (HGDP). We performed whole-genome sequencing using Illumina Hi-Seq 2000 to  a median sequencing depth of 5.5x per individual. After stringent quality control filters, we call over 17 Million SNPs  across the three populations, 32% of them novel (relative to dbSNP 132). Genotype accuracy after imputation was  assessed using genotype data from the Illumina OMNI1 SNP array, and error rates were found to be comparable to  other low-coverage studies (< 3% for most individuals). Preliminary results show relatively low genetic differentiation  between the Baka and the Nzebi (mean FST = 0.026), whereas the Mbuti show higher differentiation to both Baka and  Nzebi (mean FST = 0.060 and 0.070, respectively). Furthermore, we find that alleles previously found to be associated with height in other populations are not enriched for the “small” alleles in the Pygmy populations. We find a number of  highly differentiated genomic regions as candidate loci for height differentiation, which will be verified using simulations  under the best-fit demographic model, inferred from multi-dimensional allele frequency spectra using DaDi. Our dataset  will allow a detailed investigation of the demographic history and the genomics of adaptation in these populations.

Genetic structure in North African human populations and the gene flow to Southern Europe

Laura R Botigué 1 , Brenna M Henn 2 , Simon Gravel 2 , Jaume Bertranpetit 1 , Carlos D Bustamante 2 , David Comas 1 1 Institut de Biologia Evolutiva (IBE, CSIC-UPF), Barcelona, Spain,  2 Stanford University, Stanford CA, USA Despite being in the African continent and at the shores of the Mediterranean, North African populations might have  experienced a different population history compared to their neighbours. However, the extent of their genetic divergence  and gene flow from neighbouring populations is poorly understood. In order to establish the genetic structure of North  Africans and the gene flow with the Near East, Europe and sub-Saharan Africa, a genomewide SNP genotyping array  data (730,000 sites) from several North African and Spanish populations were analysed and compared to a set of  African, European and Middle Eastern samples. We identify a complex pattern of autochthonous, European, Near  Eastern, and sub-Saharan components in extant North African populations; where the autochthonous component  diverged from the European and Near Eastern component more than 12,000 years ago, pointing to a pre-Neolithic  ‘‘back-to-Africa’’ gene flow. To estimate the time of migration from sub-Saharan populations into North Africa, we  implement a maximum likelihood dating method based on the frequency and length distribution of migrant tracts, which  has suggested a migration of western African origin into Morocco ~1,200 years ago and a migration of individuals with  Nilotic ancestry into Egypt ~ 750 years ago.  We characterize broad patterns of recent gene flow between Europe and Africa, with a gradient of recent African  ancestry that is highest in southwestern Europe and decreases in northern latitudes. The elevated shared African  ancestry in SW Europe (up to 20% of the individuals’ genomes) can be traced to populations in the North African  Maghreb. Our results, based on both allele-frequencies and shared haplotypes, demonstrate that recent migrations from  North Africa substantially contribute to the higher genetic diversity in southwestern Europe

Estimating a date of mixture of ancestral South Asian populations

Priya Moorjani 1,2 , Nick Patterson 2 , Periasamy Govindaraj 3 , Danish Saleheen 4 , John Danesh 4 , Lalji Singh* 3,5 ,  Kumarasamy Thangaraj* 3 , David Reich* 1,2 1 Harvard University, Boston, Massachusetts, USA,  2 Broad Institute, Cambridge, Massachusetts, USA,  3 Centre for  Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India,  4 Dept of Public Health and Care, University of  Cambridge, Cambridge, UK,  5 Genome Foundation, Hyderabad, Andhra Pradesh, India Linguistic and genetic studies have demonstrated that almost all groups in South Asia today descend from a mixture of  two highly divergent populations: Ancestral North Indians (ANI) related to Central Asians, Middle Easterners and  Europeans, and Ancestral South Indians (ASI) not related to any populations outside the Indian subcontinent. ANI and  ASI have been estimated to have diverged from a common ancestor as much as 60,000 years ago, but the date of the  ANI-ASI mixture is unknown. Here we analyze data from about 60 South Asian groups to estimate that major ANI-ASI  mixture occurred 1,200-4,000 years ago. Some mixture may also be older—beyond the time we can query using  admixture linkage disequilibrium—since it is universal throughout the subcontinent: present in every group speaking  Indo-European or Dravidian languages, in all caste levels, and in primitive tribes. After the ANI-ASI mixture that  occurred within the last four thousand years, a cultural shift led to widespread endogamy, decreasing the rate of  additional mixture.   

Long IBD in Europeans and recent population history 

Peter Ralph, Graham Coop  UC Davis, Davis, CA, USA  

Numbers of common ancestors shared at various points in time across populations  can tell us about recent demography, migration, and population movements.  These rates of shared ancestry over tens of generations can be inferred from  genomic data, thereby dramatically increasing our ability to infer population  history much more recent than was previously possible with population genetic  techniques.  We have analyzed patterns of IBD in a dataset of thousands of  Europeans from across the continent, which provide a window into recent  European geographic structure and migration.   

Gene flow between human populations during the exodus from Africa, and the timeline of recent human  evolution  

Aylwyn Scally, Richard Durbin  Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK 

We present a novel test for historical gene flow between populations using unphased genotypes in present-day  individuals, based on the sharing of derived alleles and making a minimal set of assumptions about their demographic  history. We apply this test to data for three human individuals of African, European and Asian ancestry. We find that the  joint distribution of European and Asian genotypes is compatible with these populations having separated cleanly at  some time in the past without subsequent genetic exchange. However the same is not true of the European-African and  Asian-African distributions, which instead suggest an extended period of continued exchange between African and nonAfrican populations after their initial separation. 

We discuss this in comparison with recent models and estimates of separation time between these populations. We  also consider the impact of recent direct experimental studies of the human mutation rate, which suggest rates of  around 0.5 × 10 -9  bp -1  y -1 , substantially lower than prior estimates of 1 × 10 -9  bp -1  y -1  obtained from calibration against  the primate fossil record. We show that in several places the lower rate, implying older dates, yields better agreement  between genetic and non-genetic (paleoanthropological and archaeological) evidence for events surrounding the  exodus of modern humans from Africa and their dispersion worldwide.

Long-term presence versus recent admixture: Bayesian and approximate-Bayesian analyses of genetic  diversity of human populations in Central Asia 

Friso Palstra, Evelyne Heyer, Frederic Austerlitz  Eco-anthropologie et Ethnobiologie UMR 7206 CNRS, Equipe Genetique des Populations Humaines, Museum National  d'Histoire Naturelle, Paris, France 

A long-standing goal in population genetics is to unravel the relative importance of evolutionary forces that shape  genetic diversity. Here we focus on human populations in Central Asia, a region that has long been known to contain  the highest genetic diversity on the Eurasian continent. However, whether this variation principally reflects long-term  presence, or rather the result of admixture associated with repeated migrations into this region in more recent historical  times, remains unclear. Here we investigate the underlying demographic history of Central Asian populations in explicit  relation to Western Europe, Eastern Asia and the Middle East. For this purpose we employ both full Bayesian and  approximate-Bayesian analyses of nuclear genetic diversity in 20 unlinked non-coding resequenced DNA regions,  known to be at least 200 kb apart from any known gene, mRNA or spliced EST (total length of 24 kb), and 22 unlinked  microsatellite loci.   

Using an approximate Bayesian framework, we find that present patterns of genetic diversity in Central Asia may be  best explained by a demographic history which combines long-term presence of some ethnic groups (Indo-Iranians)  with a more recent admixed origin of other groups (Turco-Mongols). Interestingly, the results also provide indications  that this region might have genetically influenced Western European populations, rather than vice versa. A further  evaluation in MCMC-based Bayesian analyses of isolation-with-migration models confirms the different times of  establishment of ethnic groups, and suggests gene flow into Central Asia from the east. The results from the  approximate Bayesian and full Bayesian analyses are thus largely congruent. In conclusion, these analyses illustrate  the power of Bayesian inference on genetic data and suggest that the high genetic diversity in Central Asia reflects both  long-term presence and admixture in more recent historical times. 

Population structure and evidence of selection in the Khoe-San and Coloured populations from southern Africa 

Carina Schlebusch 1 , Pontus Skoglund 1 , Per Sjödin 1 , Lucie Gattepaille 1 , Sen Li 1 , Flora Jay 2 , Dena Hernandez 3 , Andrew  Singleton 3 , Michael Blum 2 , Himla Soodyall 4,5 , Mattias Jakobsson 1 1 Uppsala University, Uppsala, Sweden,  2 Université Joseph Fourier, Grenoble, France,  3 National Institute on Aging (NIH),  Bethesda, USA,  4 University of the Witwatersrand, Johannesburg, South Africa,  5 National Health Laboratory Service,  Johannesburg, South Africa  

The San and Khoe people currently represent remnant groups of a much larger and widely distributed population of  hunter-gatherers and pastoralists who had exclusive occupation of southern Africa before the arrival of Bantu-speaking  groups in the past 1,200 years and sea-borne immigrants within the last 350 years. Mitochondrial DNA, Y-chromosome  and autosomal studies conducted on a few San groups revealed that they harbour some of the most divergent lineages  found in living peoples throughout the world.   

We used autosomal data to characterize patterns of genetic variation among southern African individuals in order to  understand human evolutionary history, in particular the demographic history of Africa. To this end, we successfully  genotyped ~ 2.3 million genome wide SNP markers in 220 individuals, comprising seven Khoe-San, two Coloured and  two Bantu-speaking groups from southern Africa. After quality filtering, the data were combined with publicly available  SNP data from other African populations to investigate stratification and demography of African populations.  

We also  applied a newly developed method of estimating population topology and divergence times. Genotypes and inferred  haplotypes were used to assess genetic diversity, patterns of haplotype variation and linkage disequilibrium in different  populations.  We found that six of the seven Khoe-San populations form a common population lineage basal to all other modern  human populations. The studied Khoe-San populations are genetically distinct, with diverse histories of gene flow with  surrounding populations. A clear geographic structuring among Khoe-San groups was observed, the northern and  southern Khoe-San groups were most distinct from each other with the central Khoe-San group being intermediate. The  Khwe group contained variation that distinguished it from other Khoe-San groups. Population divergence within the  Khoe-San group is approximately 1/3 as ancient as the divergence of the Khoe-San as a whole to other human  populations (on the same order as the time of divergence between West Africans and Eurasians). Genetic diversity in  some, but not all, Khoe-San populations is among the highest worldwide, but it is influenced by recent admixture. We  furthermore find evidence of a Nilo-Saharan ancestral component in certain Khoe-San groups, possibly related to the  introduction of pastoralism to southern Africa.   

We searched for signatures of selection in the different population groups by scanning for differentiated genome-regions  between populations and scanning for extended runs of haplotype homozygosity within populations. By means of the  selection scans, we found evidence for diverse adaptations in groups with different demographic histories and modes of  subsistence. 

Impacts of life-style on human evolutionary history: A genome-wide comparison of herder and farmer  populations in Central Asia 

Michael C. Fontaine 1,2 , Laure Segurel 2,3 , Christine Lonjou 4 , Tatiana Hegay 5 , Almaz Aldashev 6 , Evelyne Heyer 2 , Frederic  Austerlitz 1,2 1 Ecology, Systematics & Evolution. UMR8079 Univ. Paris Sud - CNRS - AgroParisTech, Orsay, France,  2 EcoAnthropologie et Ethnobiologie, UMR 7206 CNRS, MNHN, Univ Paris Diderot, Sorbonne Paris Cite, Paris, France, 3 Department of Human Genetics, University of Chicago, Chicago, USA,  4 C2BiG (Centre de  Bioinformatique/Biostatistique Genomique d’Ile de France), Plateforme Post-genomique P3S, Hopital Pitie Salpetriere,  Paris, France,  5 Uzbek Academy of Sciences, Institute of Immunology, Tashkent, Uzbekistan,  6 Institute of Molecular  Biology and Medicine, National Center of Cardiology and Internal Medicine, Bishkek,  

Kyrgyzstan Human populations use a variety of subsistence strategies to exploit an exceptionally broad range of habitats and  dietary components. These aspects of human environments have changed dramatically during human evolution, giving  rise to new selective pressures. Here we focused on two populations in Central Asia with long-term contrasted lifestyles:  Kyrgyz’s that are traditionally nomadic herders, with a traditional diet based on meat and milk products, and Tajiks that  are traditionally agriculturalists, with a traditional diet based mostly on cereals. We genotyped 93 individuals for more  than 600,000 SNP markers (Human-660W-Quad-V1.0 from Illumina) spread across the genome. We first analysed the  population structure of these two populations in the world-wide context by combining our results with other available  genome-wide data. Principal component and Bayesian clustering analyses revealed that Tajiks and Kirgiz’s are both  admixed populations which differed however from each other with respect to their ancestry proportions: Tajiks display a  much larger proportion of common ancestry with European populations while Kirgiz’s share a larger common ancestry  with Asiatic populations. We then examined the region of the genome displaying unusual population differentiation  between these two populations to detect natural selection and checked whether they were specific to Central Asia or  not. We complemented these analyses with haplotype-based analyses of selection. 

Bayesian inference of the demographic history of Niger-Congo speaking populations 

Isabel Alves 1,2 , Lounès Chikhi 2,3 , Laurent Excoffier 1,4 1 CMPG, Institute of Ecology and Evolution, Berne, Switzerland,  2 Population and Conservation Genetics Group, Instituto  Gulbenkian de Ciência, Oeiras, Portugal,  3 CNRS, Université Paul Sabatier, ENFA, Toulouse, France,  4 Swiss Institute of  Bioinformatics, Lausanne, Switzerland  

The Niger-Congo phylum encompasses more than 1500 languages spread over sub-Saharan Africa. This current wide  range is mostly due to the spread of Bantu-speaking people across sub-equatorial regions in the last 4000-5000 years.  Although several genetic studies have focused on the evolutionary history of Bantu-speaking groups, much less effort  has been put into the relationship between Bantu and non-Bantu Niger-Congo groups. Additionally, archaeological and  linguistic evidence suggest that the spread of these populations occurred in distinct directions from the core region  located in what is now the border between Nigeria and Cameroon towards West and South Africa, respectively. We  have performed coalescent simulations within an approximate Bayesian computation (ABC) framework in order to  statistically evaluate the relative probability of alternative models of the spread of Niger-Congo speakers and to infer  demographic parameters underlying these important migration events. We have analysed 61 high-quality microsatellite  markers, genotyped in 130 individuals from three Bantu and three non Bantu-speaking populations, representing a  "Southern wave" or the Bantu expansion, and a "Western wave", respectively. Preliminary results suggest that models  inspired by a spatial spread of the populations are better supported than classical isolation with migration (IM) models.  We also find that Niger-Congo populations currently maintain high levels of gene flow with their neighbours, and that  they expanded from a single source between 200 and 600 generations, even though available genetic data do not  provide enough information to accurately infer these demographic parameters.

A genetic study of skin pigmentation variation in India  

Mircea Iliescu1 , Chandana Basu Mallick 2,3 , Niraj Rai 4 , Anshuman Mishra 4 , Gyaneshwer Chaubey 2 , Rakesh Tamang 4 ,  Märt Möls 3 , Rie Goto 1 , Georgi Hudjashov 2,3 , Srilakshmi Raj 1 , Ramasamy Pitchappan 5 , CG Nicholas Mascie-Taylor 1 , Lalji  Singh 4,6 , Marta Mirazon-Lahr 7 , Mait Metspalu 2,3 , Kumarasamy Thangaraj 4 , Toomas Kivisild 1,3 1 Division of Biological Anthropology, University of Cambridge, Cambridge, UK,  2 Evolutionary Biology Group, Estonian  Biocentre, Tartu, Estonia,  3 Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia,  4 Centre for Cellular  and Molecular Biology, Hyderabad, India,  5 Chettinad Academy of Research and Education, Chettinad Health City,  Chennai, India,  6 Banaras Hindu University, Varanasi, India,  7 Leverhulme Centre for Human Evolutionary Studies,  Division of Biological Anthropology, University of Cambridge, Cambridge, UK  

Human skin colour is a polygenic trait that is primarily determined by the amount and type of melanin produced in the  skin. The pigmentation variation between human populations across the world is highly correlated with geographic  latitude and the amount of UV radiation. Association studies together with research involving different model organisms  and coat colour variation have largely contributed to the identification of more than 378 pigmentation candidate genes.  These include TYR OCA2, that are known to cause albinism, MC1R responsible for the red hair phenotype, and genes  such as MATP, SLC24A5 and ASIP that are involved in normal pigmentation variation. In particular, SLC24A5 has been  shown to explain one third of the pigmentation difference between Europeans and Africans. However, the same gene  cannot explain the lighter East Asian phenotype; therefore, light pigmentation could be the result of convergent  evolution. A study on UK residents of Pakistani, Indian and Bangladeshi descent found significant association of  SLC24A5, SLC45A2 and TYR genes with skin colour. While these genes may explain a significant proportion of  interethnic differences in skin colour, it is not clear how much variation such genes explain within Indian populations  who are known for their high level of diversity of pigmentation. We have tested 15 candidate SNPs for association with  melanin index in a large sample of 1300 individuals, from three related castes native to South India. Using logistic  regression model we found that SLC24A5 functional SNP, rs1426654, is strongly associated with pigmentation in our  sample and explains alone more than half of the skin colour difference between the light and the dark group of  individuals. Conversely, the other tested SNPs fail to show any significance; this strongly argues in favour of one gene  having a major effect on skin pigmentation within ethnic groups of South India, with other genes having small additional  effects on this trait. We genotyped the SLC24A5 variant in over 40 populations across India and found that latitudinal  differences alone cannot explain its frequency patterns in the subcontinent. Key questions arising from this research are  when and where did the light skin variant enter South Asia and the manner and reason for it spreading across the Indian  sub-continent. Hence, a comprehensive view of skin colour evolution requires that in depth sequence information be  corroborated with population (genetic) history and with ancient DNA data of past populations of Eurasia. 

SMBE 2012 abstracts (part I)

Some abstracts of interest from SMBE 2012. Part II will follow.

Reconstructing demographic histories from long tracts of DNA sequence identity 

Kelley Harris 1 , Rasmus Nielsen 1,2 1 UC Berkeley, Berkeley, CA, USA,  2 University of Copenhagen, Copenhagen, Denmark 
There has been recent excitement and debate about the details of human demographic history, involving gene flow that  has occurred between populations as well as the extent and timing of bottlenecks and periods of population growth.  Much of the debate concerns the timing of past admixture events; for example, whether Neanderthals exchanged  genetic material with the ancestors of non-Africans before before or after they left Africa. Here, we present a method for  using sequence data to jointly estimate the timing and magnitude of past genetic exchanges, along with population  divergence times and changes in effective population size. To achieve this, we look at the length distribution of regions  that are shared identical by state (IBS) and maximize an analytic composite likelihood that we derive from the  sequentially Markov coalescent (SMC). Recent gene flow between populations leaves behind long tracts of identity by  descent (IBD), and these tracts give our method its power by influencing the distribution of shared IBS tracts. However,  since IBS tracts are directly observable, we do not need to infer the precise locations of IBD tracts. In this way, we can  accurately estimate admixture times for relatively ancient events where admixture mapping is not possible, and in  simulated data we show excellent power to characterize admixture pulses that occurred 100 to several hundred  generations ago. When we study the IBS tracts shared between and within the populations sequenced by the 1000  Genomes consortium, we find evidence that there was no significant gene flow between Europeans and Asians within  the past few hundred generations. It also looks unlikely that the Yorubans of Nigeria interbred with Europeans or Asians  in a population-specific way, though there may have been admixture between Africans and an ancestral non-African  population. 

Which way did they go? Detecting directional migration from genetic data

Benjamin Peter, Montgomery Slatkin University of California, Berkeley, Berkeley, USA  

Range expansions and colonizations are ubiquitous in many species and are studied from many different perspectives in e.g. anthropology, biogeography and invasion biology. It has been well established that these colonization events lead to a loss of genetic diversity and that in many cases it is possible to infer the history of a species' range from present-day genetic data. Previous approaches were mainly based on within-population measures of diversity such as heterozygosity, which then have been compared between populations. However, it is also well established that these statistics are susceptible to confounding demographic factors such as unequal subpopulation sizes or population size changes. In this study, we propose a novel method using data from multiple populations to infer a population's history. Our approach is based on a statistic that detects asymmetries in the 2D-allele frequency spectrum that occur when one population consists mostly of offspring of another population, as we expect in an expanding population. We show that our statistic is able to detect the direction of an expansion using data from multiple populations. Using simulations, we further show that our statistic is generally more powerful than previous approaches and that it is robust to a wide array of confounding demographic factors. We further illustrate the use of our statistic on several data sets for humans, Drosophila and Neurospora and show that we are both able to detect global patterns of colonization and fine-scale population structure.

Populations genetics of the Neolithic transition

Joachim Burger 1 , Mark Thomas 2,3 1  

Johannes Gutenberg University, Institute of Anthropology, D-55128 Mainz, Germany,  2 Research Department of  Genetics, Evolution and Environment, University College London, Wolfson House, 4 Stephenson Way, London NW1  2HE, UK,  3 Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Norbyvagen 18D, SE- 752 36 Uppsala, Sweden     

About 11,000 years ago, a change in human lifestyle took place in the territories of present-day western Iran, the Levant  region and south-east Anatolia, which is characterised particularly by four factors: the people founded permanent  settlements with buildings for various functions; plants such as Einkorn and beans were cultivated; goats, sheep, pigs  and cattle were domesticated; a new kind of culture evolved, that became conspicuous with the appearance of a new  material culture including ground stone tools and later, pottery products. The transition from the partly nomadic huntergatherer subsistence strategy to a settled lifestyle based on food production is also known as the “Neolithic Revolution”.  About 8,500 years ago, the Neolithic culture spread to the southeast of Europe and later expanded episodically across  central and northern Europe. The extent to which this movement of a farming culture was accompanied by a movement  of people, as opposed to just a spread of ideas and skills, has been a subject of considerable debate and dispute  over  the last 100 years. Population genetic computer simulations of genetic data from ancient human remains, based on  coalescent theory have shown that the early Neolithic farmers could not have been descended just from the later  hunter-gatherers of central Europe (Bramanti et al. 2009). As the hunter-gatherers had already been settled in Central  Europe since the retreat of the glaciers 20 kya, Neolithic famers must have migrated into this area.   

There is good evidence of cultural contact between hunter-gatherers and early farmers in central Europe. Whether the  exchange of hunting tools also led also to the exchange of men is still not clear, as Y-chromosomal DNA has not yet  been studied systematically in ancient human remains. Moreover, ancient DNA evidence is now emerging that other  regions don/t follow the patterns of population discontinuity observed in Central Europe. While the overall results  support a model of demic diffusion of farmers from southeastern Europe, or even further East, in to Central Europe, it is  very likely that modern populations in most parts of Europe were formed by varying degrees of admixture between  incoming farmers and indigenous hunter-gatherers. Analyses of the appropriate neutral and phenotypically informative  markers using next generation sequencing technologies will provide more information on this in the near future. 

Population genetic properties of time serial data with examples from ancient population-genomic data 

Mattias Jakobsson Uppsala University, Uppsala, Sweden  

Extracting genetic information from ancient material has for long been hampered by numerous difficulties since its first  steps some two decades ago, but in the last few years, many of these problems have been solved and the use of  ancient DNA (aDNA) is now beginning to show its full potential. We will likely see a wealth of genomic data from ancient  populations, but the statistical properties of time-structured genetic samples are considerably less explored than  population genetic patterns arising from spatial structure. Using simulations, we explore and highlight features of  temporal structure and spatial structure, such as an 'isolation-by-time' effect that is similar to isolation-by-distance.  Using model- and simulation-based approaches, we can now make novel inferences about demographic and  evolutionary questions from time serial data. We will discuss examples from the long standing debate about the  introduction of farming in Europe and question about archaic ancestry in East Asia using paleogenomic data.  

Inferences on dog domestication - genetic analysis of the most ancient dogs utilizing DNA capture arrays

Olaf Thalmann 1,2 , Daniel Greenfield 2 , Matthias Meyer 3 , Susanna Sawyer 3 , Pin Cui 3 , Mietje Germonpre 4 , Mikhail V.  Sablin 5 , Francesc Lopez-Giraldez 9 , Daniel LePont 1 , Brian Worthington 10 , Jeff P. Blick 6 , Jeniffer A. Leonard 7 , Richard E.  Green 8 , Robert K. Wayne 2 1 University of Turku, Turku, Finland,  2 University of California, Los Angeles, USA,  3 Max Planck Institute for Evolutionary  Anthropology, Leipzig, Germany,  4 Royal Belgian Institute of Natural Sciences, Brussels, Belgium,  5 Zoological Institute  RAS, Saint-Petersburg, Russia,  6 Georgia College & State University, Milledgeville, USA,  7 Estacion Biologica de  Donana- CSIC, Seville, Spain,  8 University of California, Santa Cruz, USA,  9 Yale University, New Haven, USA, 10 Southeastern Archaeological Research, Inc., Newberry, USA 

The geographical and temporal origin of the dog is controversial. Genetic data suggest a domestication event in Asia or  the Middle East about 15,000 - 30,000 years ago, whereas the oldest dog-like fossils are found in Europe dating to over  30 thousand years ago. We genetically analyzed the remains of 14 prehistoric wolves and dogs including some of the  oldest dog remains described from the New and Old World. Utilizing array based DNA capture techniques coupled with  Illumina double indexed sequencing, we targeted a total of ~750,000 nucleotides in each of the ancient canids and  additional 20 contemporary wolves from North America and Eurasia. The sequence information comprised the complete  mitochondrial genome, 3,000 SNPs previously identified as highly informative for differentiating dogs from wolves,  exonic sequences from 62 potential domestication genes and ~150,000 nucleotides of non-coding regions spread  throughout the genome.   Initial analyses reveal that we have successfully captured and sequenced the complete mitochondrial genome with high  coverage as wells as a substantial number of autosomal fragments from ten prehistoric canids and all contemporary  wolves. Phylogenetic analysis combining the complete mitochondrial genomes of the prehistoric canids with those of a  large collection of modern dogs and wolves result in a statistically well supported tree. While some haplotypes cluster  within modern dogs or wolves, others show a basal placement in the phylogeny. The latter finding might support a  previous notion that an aberrant lineage of dog-like canids might have existed throughout the northern hemisphere  during the late Pleistocene and became globally extinct during the last 20,000 years. We will test this hypothesis by  investigating the autosomal loci and employ sophisticated phylogenetic analyses, demographic modeling and selection  scans to better understand the influence of early human society and artificial selection on the canine genome.

Admixed human genomes reveal complex demographic patterns from early modern humans to the  contemporary era 

Simon Gravel 1 , Jeffrey M Kidd 2 , Jake K Byrnes 1 , Andres Moreno Estrada 1 , Fouad Zakharia 1 , Shaila Musharoff 1 ,  Francisco M De La Vega 1 , Carlos D Bustamante 1 1 Stanford University, Stanford, CA, USA,  2 University of Michigan, Ann Arbor, MI, USA     

A substantial proportion of humans are "admixed", in the sense that their recent ancestors belong to statistically distinct  groups. This needs to be accounted for if unbiased inference and associations are to be performed. We present a  diversity of methods for the analysis of whole-genome sequence data from admixed individuals, and apply them to 50  genomes sequenced by Complete Genomics, including 4 Mexican-Americans, 4 African-Americans and 2 individuals  from Puerto Rico, together with SNP genotype data from hundreds of additional samples.     

Many methods have been presented recently to infer the population of origin of specific loci along the genomes of  admixed individuals, leading to inferred mosaics of ancestry.  We first propose a simple Markov model that relates the  time-dependent migration history to the inferred patterns of local ancestry. We use this framework to infer the timing of  admixture and to differentiate between punctual and continuous models of migration: using demographic models that  are consistent with both historical records and genetic data, we find evidence for continuous migration patterns in both  Mexican and African-American populations.     

We also propose models to study the longer-term evolution of the ancestral populations, by considering the allele  frequency distribution, pairwise TMRCA's, and a simple extension of the recently introduced Pairwise Sequentially  Markovian Coalescent approach for demographic inference. The inferred source population demographic histories are  in broad agreement with previous results for European and West-African populations, and the inferred demography for  the Native source population closely follows the European one until about 20,000 years ago. Taken together, whole  genome sequencing and local ancestry assignment therefore permit inferences about long-term histories of unsampled  ancestral populations and highlights recent historical demographic processes that altered patterns of variation observed  in admixed populations. 

A genomewide map of Neandertal ancestry in modern humans

Sriram Sankararaman 1,2 , Nick Patterson 2 , Swapan Mallick 1,2 , Svante Paabo 3 , David Reich 1,2 1 Harvard Medical School, Boston, USA, 2 Broad Institute of Harvard and MIT, Cambridge, USA, 3 Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany 

Analysis of the genomes of archaic hominins, such as Neandertals and Denisovans, has revealed that these groups have contributed to the genetic variation of modern human populations. Yet, we know little about how these ancient mixtures have shaped the genetic structure of human populations and even less about their impact on human evolution. To answer these questions systematically, we need a map of archaic ancestry i.e., a map that labels whether each region of an individual genome is descended from these archaics.

Building such a map is technically challenging because of the antiquity of these gene flow events. We have identified signatures based on patterns of variation at single SNPs as well as haplotypes that are informative of ancient gene flow.

We propose a principled method based on the statistical framework of Conditional Random Fields (CRFs) that integrates these patterns leading to highly accurate predictions. We applied our method to polymorphism data in European and East Asian individuals from the 1000 genomes project, in conjunction with the draft sequence of the Neandertal genome, to obtain the first genomewide map of Neandertal ancestry. Analysis of this map reveals several findings:

1. We identify around 35,000 Neandertal-derived alleles in Europeans and 21,000 in East Asians.

2. The map allows us to identify Neandertal alleles that have been the target of selection since introgression. We identified over 100 regions in which the frequency of Neandertal ancestry is extremely unlikely under a model of neutral evolution. The highest frequency region on chromosome 4 has a frequency of Neandertal ancestry of about 85% in Europe and overlaps CLOCK, a key gene in Circadian function in mammals. The high frequency, Neandertal-derived variant is specific to Europeans; it is not very common in East Asians. This gene has been found in other selection scans in Eurasian populations, but has never before been linked to Neandertal gene flow.

3. Several of the Neandertal-derived alleles identified in 1) above are found in the >6,000 SNPs associated with common diseases listed in the NHGRI catalog. These Neandertal derived variants are found to be risk variants associated with obesity and protective variants against breast cancer.

4. We also investigate the possibility of using this map to reconstruct the genome of the introgressing Neandertal. Using the ancestries in Europe and East Asia, we can reconstruct about 600 Mb which we expect to increase with larger samples and additional populations.

Origins and evolution of the Etruscans’ DNA

Silvia Ghirotto 1 , Francesca Tassi 1 , Erica Fumagalli 2,1 , Vincenza Colonna 3,1 , Anna Sandionigi 4 , Martina Lari 4 , Stefania Vai 4 , Emmanuele Petiti 4 , Giorgio Corti 5 , Ermanno Rizzi 5 , Gianluca De Bellis 5 , David Caramelli 4 , Guido Barbujani 1 1 Department of Biology and Evolution, University of Ferrara, Ferrara, Italy, 2 Department of Biotechnologies and BiosciencesUniversity of Milano-Bicocca, Milano, Italy, 3 Institute of Genetics e Biophysics "Adriano Buzzati-Traverso", National Research Council, Napoli, Italy, 4 Department of Evolutionary Biology, University of Firenze, Firenze, Italy, 5 Institute for Biomedical Technologies (ITB), National Research Council (CNR), Milano, Italy

The Etruscan culture is documented in Etruria, Central Italy, from the 7 th to the 1 st century BC. For more than 2,000 years there has been disagreement on the Etruscans’ biological origins, whether local or in Anatolia. Genetic affinities with both Tuscan and Anatolian populations have been reported, but so far all attempts have failed to fit the Etruscans’ and modern populations in the same genealogy. We extracted and typed mitochondrial DNA of 14 individuals buried in two Etruscan necropoleis, analyzing them along with other Etruscan and Medieval samples, and 4,910 contemporary individuals. Comparing ancient and modern diversity with the results of millions of computer simulations, we show that the Etruscans can be considered ancestral, with a high degree of confidence, to the modern inhabitants of two communities, Casentino and Volterra, but not to most contemporary populations dwelling in the former Etruscan homeland. We also estimate that the genetic links between Tuscany and Anatolia date back to at least 5,000 years ago, strongly suggesting that the Etruscan culture developed locally, without a significant contribution of recent Anatolian immigrants.

Human population genomics in time and space: paleogenomics of populations in Bulgaria

Meredith L. Carpenter 1 , Hannes Schroeder 2 , Nikola Theodossiev 3 , M. Thomas P. Gilbert 2 , Carlos D. Bustamante 1 1 Department of Genetics, Stanford University, Stanford, CA, USA, 2 Centre for Geogenetics, University of Copenhagen, Copenhagen, Denmark, 3 Department of Archaeology, Sofia University, Sofia, Bulgaria

With a few exceptions, most ancient human DNA studies to date have restricted their analysis to the mitochondrial DNA (mtDNA) and Y chromosome. These approaches have led to some interesting theories regarding the spread of human populations; however, they are inherently limited by their use of these two non-recombining markers, which are subject to forces such as genetic drift and natural selection and also represent only the histories of the female and male lines, respectively, from which they descend. Recently, the whole genomes of several ancient individuals have been sequenced. These genomes yielded much more information about the individuals’ ancestry than their mtDNA alone; nevertheless, a single ancient individual is not sufficient for population genetic analyses. Thus, the goal of our study is to sequence the genomes of multiple ancient individuals from the same population. This type of study has the potential to dramatically improve our ability to address demographic questions about ancient human populations. We have begun the low-coverage sequencing of genomic DNA from the teeth of 16 individuals from different time periods (1500 BC-400 BC) in Bulgaria, and we plan to ultimately extend the study to at least 50 ancient Bulgarian individuals from the Neolithic to the Iron Age (6300 BC-400 BC). The results of these initial experiments will be presented, including the identification of mtDNA haplogroups and initial population genetic analyses. Ultimately, we plan to analyze whole-genome sequence variation in these individuals and to compare it to variation present in modern populations. This will be the first systematic population-level study of ancient human genomes and therefore will allow us address demographic questions that have previously been restricted to the realm of theoretical modeling using extant populations.

Horse domestication: a computer simulation approach

Michela Leonardi 1 , Christine Weber 1 , Norbert Benecke 2 , Mark G. Thomas 3,4 , Joachim Burger 1 1 AG Palaeogenetik, Institute of Anthropology, SBII, Johannes Gutenberg University, Colonel Kleinmann-Weg 2, 55128, Mainz, Germany, 2 German Archaeological Institute, Im Dol 4-6, 14165, Berlin, Germany, 3 Research Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, WC1E 6BT, London, UK, 4 Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Norbyvagen 18D, SE-752 36, Uppsala, Sweden

The domestication of horse played a key role in human history. It seems to have happened far both in time and space from the domestication of other ungulates such as cattle, pig, sheep and goat. Archaeological studies, nevertheless, failed in determining exactly the region and modality for horse domestication: several centers have been proposed (at least one in Europe and one in Central Asia) and the relationship between wild and early domestic populations are not clear. From a genetic point of view a phylogenetic approach on modern mitochondrial diversity could not find any structure related with geography or breeds. In the last decade ancient DNA became an important tool to reconstruct past demography. We obtained more than 100 HVR I sequences from pre domestic and domestic specimens found in Europe and Central Asia. After collecting all the previously published ancient and modern comparable sequences from the sub mentioned regions, computer simulations with a Bayesian approach were performed in order to test demographic models related with single or multiple domestications with or without gene flow. A single domestication appears to be unrealistic on the basis of mitochondrial data, while possible model of multiple domestications will be discussed.

The complete mitochondrial genome of a third individual from Denisova Cave

Susanna Sawyer 1 , Bence Viola 1 , Marie-Theres Gansauge 1 , Michael Shunkov 2 , Anatoly Derevianko 2 , Svante Paabo 1 1 Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany, 2 Paleolithic Department, Institute of Archaeology and Ethnography, Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russia

A draft genome sequence was determined in 2010 from a small finger bone found in Denisova Cave in southern Siberia and was recently completed to 30-fold coverage. Its analysis reveals that it derived from an individual that belonged to a population related to, but distinct from, Neandertals. A large molar has also been described from Denisova Cave and shown to carry an mtDNA genome closely related to that of the finger bone. A second molar was found in Denisova Cave in 2010. We have captured and sequenced the complete mitochondrial genome of this tooth. While the mtDNAs of the finger bone and the first molar differ at only two nucleotide positions, they carry 86 and 84 differences, respectively, to the second molar. Thus, the maximum amount of mtDNA differences observed among these three Denisovans found within one cave is almost twice as large as the maximum differences seen among six Neandertals for which complete mtDNAs are available. Interestingly, the mtDNA of the second molar has a shorter branch than the other two Denisovan mtDNAs, suggesting that it may be older than the others.