Genomic regions under positive selection harbor variation linked for example to adaptation. Most tools for detecting
positively selected variants have computational resource requirements rendering them impractical on population
genomic datasets with hundreds of thousands of individuals or more. We have developed and implemented an efficient haplotype-based approach able to scan large datasets and accurately detect positive selection. We achieve this
by combining a pattern matching approach based on the positional Burrows–Wheeler transform with model-based
inference which only requires the evaluation of closed-form expressions. We evaluate our approach with simulations,
and find it to be both sensitive and specific. The computational resource requirements quantified using UK Biobank
data indicate that our implementation is scalable to population genomic datasets with millions of individuals. Our
approach may serve as an algorithmic blueprint for the era of “big data” genomics: a combinatorial core coupled with
statistical inference in closed form.

Benedikt Kirsch-Gerweck, Leonard Bohnenkämper, Michel T. Henrichs, Jarno N. Alanko, Hideo Bannai, Bastien Cazaux, Pierre Peterlongo, Joachim Burger, Jens Stoye and Yoan Diekmann (2023)

https://link.springer.com/article/10.1007/s10963-022-09169-9

It is now widely accepted that agriculture and settled village life arrived in Europe as a cultural package, carried by people migrating from Anatolia and the Aegean Basin. The putative fisher-forager site of Lepenski Vir in Serbia has long been acknowledged as an exception to this model. Here, the Mesolithic–Neolithic transition—possibly inspired by interaction with the new arrivals—was thought to have taken place autochthonously on site. Our reinterpretation, based on ancient genomes, as well as archaeological and isotopic evidence, indicates that here, too, house construction, early village society and agriculture were primarily associated with Europe’s first farmers, thus challenging the long-held view of Lepenski Vir as a Mesolithic community that adopted Neolithic practices. Although aspects of the site’s occupation, such as the trapezoidal houses, were inspired by local Mesolithic traditions, it is far from certain that the village was founded by Iron Gates foragers. A detailed timeline of population changes at the site suggests that Aegean incomers did not simply integrate into an established Mesolithic society, but rather founded new lineages and households. Iron Gates foragers and their admixed descendants largely appear to have been buried separately, on the fringes of the settlement. The diet of those buried outside in pits shows no major shift from aquatic to terrestrial food resources..

Maxime Brami, Laura Winkelbach, Ilektra Schulz, Mona Schreiber, Jens Blöcher, Yoan Diekmann, and Joachim Burger (2022)

https://link.springer.com/article/10.1007/s10963-022-09169-9

The precise genetic origins of the first Neolithic farming populations in Europe and Southwest Asia, as well as the processes and the timing of their differentiation, remain largely unknown. Demogenomic modeling of high-quality ancient genomes reveals that the early farmers of Anatolia and Europe emerged from a multiphase mixing of a Southwest Asian population with a strongly bottlenecked western hunter-gatherer population after the last glacial maximum. Moreover, the ancestors of the first farmers of Europe and Anatolia went through a period of extreme genetic drift during their westward range expansion, contributing highly to their genetic distinctiveness. This modeling elucidates the demographic processes at the root of the Neolithic transition and leads to a spatial interpretation of the population history of Southwest Asia and Europe during the late Pleistocene and early Holocene.

Nina Marchi, Laura Winkelbach, Ilektra Schulz, Maxime Brami, Zuzana Hofmanová, Jens Blöcher, Carlos S. Reyna-Blanco, Yoan Diekmann, Alexandre Thiéry, Adamandia Kapopoulou, Vivian Link, Valérie Piuz, Susanne Kreutzer, Sylwia M. Figarska, Elissavet Ganiatsou, Albert Pukaj, Travis J. Struck, Ryan N. Gutenkunst, Necmi Karul, Fokke Gerritsen, Joachim Pechtl, Joris Peters, Andrea Zeeb-Lanz, Eva Lenneis, Maria Teschler-Nicola, Sevasti Triantaphyllou, Sofija Stefanovic, Christina Papageorgopoulou, Daniel Wegmann, Joachim Burger, and Laurent Excoffier (2022)

https://www.cell.com/action/showPdf?pii=S0092-8674%2822%2900455-X

Twenty-four palaeogenomes from Mokrin, a major Early Bronze Age necropolis in southeastern Europe, were sequenced to analyse kinship between individuals and to better understand prehistoric social organization. 15 investigated individuals were involved in genetic relationships of varying degrees. The Mokrin sample resembles a genetically unstructured population, suggesting that the community’s social hierarchies were not accompanied by strict marriage barriers. We fnd evidence for female exogamy but no indications for strict patrilocality. Individual status diferences at Mokrin, as indicated by grave goods, support the inference that females could inherit status, but could not transmit status to all their sons. We further show that sons had the possibility to acquire status during their lifetimes, but not necessarily to inherit it. Taken together, these fndings suggest that Southeastern Europe in the Early Bronze Age had a signifcantly diferent family and social structure than Late Neolithic and Early Bronze Age societies of Central Europe.

Aleksandra Žegarac, Laura Winkelbach, Jens Blöcher, Yoan Diekmann, Marija Krečković Gavrilović, Marko Porčić, Biljana Stojković, Lidija Milašinović, Mona Schreiber, Daniel Wegmann, Krishna R. Veeramah, Sofija Stefanović and Joachim Burger (2021)

https://www.nature.com/articles/s41598-021-89090-x.pdf

Lactase persistence (LP), the continued expression of lactase into adulthood, is the most strongly selected single gene trait over the last 10,000 years in multiple human populations. It has been posited that the primary allele causing LP among Eurasians, rs4988235-A [1], only rose to appreciable frequencies during the Bronze and Iron Ages [2, 3], long after humans started consuming milk from domesticated animals. This rapid rise has been attributed to an influx of people from the Pontic-Caspian steppe that began around 5,000 years ago [4, 5]. We investigate the spatiotemporal spread of LP through an analysis of 14 warriors from the Tollense Bronze Age battlefield in northern Germany (∼3,200 before present, BP), the oldest large-scale conflict site north of the Alps. Genetic data indicate that these individuals represent a single unstructured Central/Northern European population. We complemented these data with genotypes of 18 individuals from the Bronze Age site Mokrin in Serbia (∼4,100 to ∼3,700 BP) and 37 individuals from Eastern Europe and the Pontic-Caspian Steppe region, predating both Bronze Age sites (∼5,980 to ∼3,980 BP). We infer low LP in all three regions, i.e., in northern Germany and South-eastern and Eastern Europe, suggesting that the surge of rs4988235 in Central and Northern Europe was unlikely caused by Steppe expansions. We estimate a selection coefficient of 0.06 and conclude that the selection was ongoing in various parts of Europe over the last 3,000 years.

Joachim Burger, Vivian Link, Jens Blöcher, Anna Schulz, Christian Sell, Zoé Pochon, Yoan Diekmann, Aleksandra Žegarac, Zuzana Hofmanová, Laura Winkelbach, Carlos S. Reyna-Blanco, Vanessa Bieker, Jörg Orschiedt, Ute Brinker, Amelie Scheu, Christoph Leuenberger, Thomas S. Bertino, Ruth Bollongino, Gundula Lidke, Sofija Stefanović, Detlef Jantzen, Elke Kaiser, Thomas Terberger, Mark G. Thomas, Krishna R. Veeramah and Daniel Wegmann (2020)

https://www.sciencedirect.com/science/article/abs/pii/S0960982220311878?via%3Dihub

Modern European genetic structure demonstrates strong correlations with geography, while genetic analysis of prehistoric humans has indicated at least two major waves of immigration from outside the continent during periods of cultural change. However, population-level genome data that could shed light on the demographic processes occurring during the intervening periods have been absent. Therefore, we generated genomic data from 41 individuals dating mostly to the late 5th/early 6th century AD from present-day Bavaria in southern Germany, including 11 whole genomes (mean depth 5.56×). In addition we developed a capture array to sequence neutral regions spanning a total of 5 Mb and 486 functional polymorphic sites to high depth (mean 72×) in all individuals. Our data indicate that while men generally had ancestry that closely resembles modern northern and central Europeans, women exhibit a very high genetic heterogeneity; this includes signals of genetic ancestry ranging from western Europe to East Asia. Particularly striking are women with artificial skull deformations; the analysis of their collective genetic ancestry suggests an origin in southeastern Europe. In addition, functional variants indicate that they also differed in visible characteristics. This example of female-biased migration indicates that complex demographic processes during the Early Medieval period may have contributed in an unexpected way to shape the modern European genetic landscape. Examination of the panel of functional loci also revealed that many alleles associated with recent positive selection were already at modern-like frequencies in European populations ∼1,500 years ago.

Krishna R. Veeramah, Andreas Rott, Melanie Groß, Lucy van Dorp, Saioa López, Karola Kirsanow, Christian Sell, Jens Blöcher, Daniel Wegmann, Vivian Link, Zuzana Hofmanová, Joris Peters, Bernd Trautmann, Anja Gairhos, Jochen Haberstroh, Bernd Päffgen, Garrett Hellenthal, Brigitte Haas-Gebhard, Michaela Harbeck and Joachim Burger (2018)

www.pnas.org/cgi/doi/10.1073/pnas.1719880115

Europe has played a major role in dog evolution, harbouring the oldest uncontested Palaeolithic remains and having been the centre of modern dog breed creation. Here we sequence the genomes of an Early and End Neolithic dog from Germany, including a sample associated with an early European farming community. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a previously suggested Late Neolithic population replacement. We find no genetic evidence to support the recent hypothesis proposing dual origins of dog domestication. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication to 20,000–40,000 years ago. Interestingly, we do not observe the extreme copy number expansion of the AMY2B gene characteristic of modern dogs that has previously been proposed as an adaptation to a starch-rich diet driven by the widespread adoption of agriculture in the Neolithic.

Laura R. Botigué, Shiya Song, Amelie Scheu, Shyamalika Gopalan, Amanda L. Pendleton, Matthew Oetjens, Angela M. Taravella, Timo Seregély, Andrea Zeeb-Lanz, Rose-Marie Arbogast, Dean Bobo, Kevin Daly, Martina Unterländer, Joachim Burger, Jeffrey M. Kidd & Krishna R. Veeramah (2017)

Nat. Commun. 8, 16082 doi:10.1038/ncomms16082

During the 1st millennium before the Common Era (BCE), nomadic tribes associated with the Iron Age Scythian culture spread over the Eurasian Steppe, covering a territory of more than 3,500 km in breadth. To understand the demographic processes behind the spread of the Scythian culture, we analysed genomic data from eight individuals and a mitochondrial dataset of 96 individuals originating in eastern and western parts of the Eurasian Steppe. Genomic inference reveals that Scythians in the east and the west of the steppe zone can best be described as a mixture of Yamnaya-related ancestry and an East Asian component. Demographic modelling suggests independent origins for eastern and western groups with ongoing gene-flow between them, plausibly explaining the striking uniformity of their material culture. We also find evidence that significant gene-flow from east to west Eurasia must have occurred early during the Iron Age.

Martina Unterländer, Friso Palstra, Iosif Lazaridis, Aleksandr Pilipenko, Zuzana Hofmanová, Melanie Groß, Christian Sell, Jens Blöcher, Karola Kirsanow, Nadin Rohland, Benjamin Rieger, Elke Kaiser, Wolfram Schier, Dimitri Pozdniakov, Aleksandr Khokhlov, Myriam Georges, Sandra Wilde, Adam Powell, Evelyne Heyer, Mathias Currat, David Reich, Zainolla Samashev, Hermann Parzinger, Vyacheslav I. Molodin & Joachim Burger (2017)

Nat. Commun. 8, 14615 doi: 10.1038/ncomms14615

Post-mortem damage (PMD) obstructs the proper analysis of ancient DNA samples. Currently, PMD can only be addressed by adjusting sequencing quality scores or by removing potentially damaged data. Here we present ATLAS, a suite of methods to analyze ancient samples that properly account for PMD. It works directly from raw BAM files and contains all necessary methods to infer patterns of PMD, recalibrate base quality scores and accurately genotype ancient DNA, along with many other useful tools. ATLAS enables the building of complete and customized pipelines for the analysis of ancient and low-depth samples in a very user-friendly way. Using simulations we show that, in the presence of PMD, a dedicated pipeline of ATLAS calls genotypes more accurately than the state of the art pipeline of GATK combined with mapDamage 2.0.

Vivian Link, Athanasios Kousathanas, Krishna Veeramah, Christian Sell, Amelie Scheu, Daniel Wegmann (2017)

bioRxiv, https://doi.org/10.1101/105346

While genetic diversity can be quantified accurately from high coverage sequencing, it is often desirable to obtain such estimates from low coverage data, either to save costs or because of low DNA quality as observed for ancient samples. Here we introduce a method to accurately infer heterozygosity probabilistically from very low coverage sequences of a single individual. The method relaxes the infinite sites assumption of previous methods, does not require a reference sequence and takes into account both variable sequencing errors and potential post-mortem damage. It is thus also applicable to non-model organisms and ancient genomes. Since error rates as reported by sequencing machines are generally distorted and require recalibration, we also introduce a method to infer accurately recalibration parameter in the presence of post-mortem damage. This method does also not require knowledge about the underlying genome sequence, but instead works from haploid data (e.g. from the X-chromosome from mammalian males) and integrates over the unknown genotypes. Using extensive simulations we show that a few Mb of haploid data is sufficient for accurate recalibration even at average coverages as low as 1-3x. At similar coverages, out method also produces very accurate estimates of heterozygosity down to 10−4 within windows of about 1Mb. We further illustrate the usefulness of our approach by inferring genome-wide patterns of diversity for several ancient human samples and found that 3,000-5,000 samples showed diversity patterns comparable to modern humans. In contrast, two European hunter-gatherer samples exhibited not only considerably lower levels of diversity than modern samples, but also highly distinct distributions of diversity along their genomes. Interestingly, these distributions were also very differently between the two samples, supporting earlier conclusions of a highly diverse and structured population in Europe prior to the arrival of farming.

Athanasios Kousathanas, Christoph Leuenberger, Vivian Link, Christian Sell, Joachim Burger and Daniel Wegmann (2016)

Genetics 205(1):317-332.

We sequenced Early Neolithic genomes from the Zagros region of Iran (eastern Fertile Crescent), where some of the earliest evidence for farming is found, and identify a previously uncharacterized population that is neither ancestral to the first European farmers nor has contributed significantly to the ancestry of modern Europeans. These people are estimated to have separated from Early Neolithic farmers in Anatolia some 46-77,000 years ago and show affinities to modern day Pakistani and Afghan populations, but particularly to Iranian Zoroastrians. We conclude that multiple, genetically differentiated hunter-gatherer populations adopted farming in SW-Asia, that components of pre-Neolithic population structure were preserved as farming spread into neighboring regions, and that the Zagros region was the cradle of eastward expansion.

Farnaz Broushaki, Mark G. Thomas, Vivian Link, Saioa López, Lucy van Dorp, Karola Kirsanow, Zuzana Hofmanová, Yoan Diekmann, Lara M. Cassidy, David Díez-del-Molino, Athanasios Kousathanas, Christian Sell, Harry K. Robson, Rui Martiniano, Jens Blöcher, Amelie Scheu, Susanne Kreutzer, Ruth Bollongino, Dean Bobo, Hossein Davudi, Olivia Munoz, Mathias Currat, Kamyar Abdi, Fereidoun Biglari, Oliver E. Craig, Daniel G. Bradley, Stephen Shennan, Krishna Veeramah, Marjan Mashkour, Daniel Wegmann, Garrett Hellenthal, Joachim Burger (2016)

Science 353: 499-503.

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Farming and sedentism first appear in southwest Asia during the early Holocene and later spread to neighboring regions, including Europe, along multiple dispersal routes. Conspicuous uncertainties remain about the relative roles of migration, cultural diffusion and admixture with local foragers in the early Neolithisation of Europe. Here we present paleogenomic data for five Neolithic individuals from northern Greece and northwestern Turkey – spanning the time and region of the earliest spread of farming into Europe. We observe striking genetic similarity both among Aegean early farmers and with those from across Europe. Our study demonstrates a direct genetic link between Mediterranean and Central European early farmers and those of Greece and Anatolia, extending the European Neolithic migratory chain all the way back to southwestern Asia.

Zuzana Hofmanová, Susanne Kreutzer, Garrett Hellenthal, Christian Sell, Yoan Diekmann, David Díez-del-Molino, Lucy van Dorp, Saioa López, Athanasios Kousathanas, Vivian Link, Karola Kirsanow, Lara M. Cassidy, Rui Martiniano, Melanie Strobel, Amelie Scheu, Kostas Kotsakis, Paul Halstead, Sevi Triantaphyllou, Nina Kyparissi-Apostolika, Dushanka-Christina Urem-Kotsou, Christina Ziota, Fotini Adaktylou, Shyamalika Gopalan, Dean M. Bobo, Laura Winkelbach, Jens Blöcher, Martina Unterländer, Christoph Leuenberger, Çiler Çilingiroğlu, Barbara Horejs, Fokke Gerritsen, Stephen Shennan, Daniel G. Bradley, Mathias Currat, Krishna R. Veeramah, Daniel Wegmann, Mark G. Thomas, Christina Papageorgopoulou, and Joachim Burger (2016)

Proc Natl Acad Sci U S A 113: 6886-6891.

Cattle domestication started in the 9(th) millennium BC in Southwest Asia. Domesticated cattle were then introduced into Europe during the Neolithic transition. However, the scarcity of palaeogenetic data from the first European domesticated cattle still inhibits the accurate reconstruction of their early demography. In this study, mitochondrial DNA from 193 ancient and 597 modern domesticated cattle (Bos taurus) from sites across Europe, Western Anatolia and Iran were analysed to provide insight into the Neolithic dispersal process and the role of the local European aurochs population during cattle domestication. Using descriptive summary statistics and serial coalescent simulations paired with approximate Bayesian computation we find: (i) decreasing genetic diversity in a southeast to northwest direction, (ii) strong correlation of genetic and geographical distances, iii) an estimated effective size of the Near Eastern female founder population of 81, iv) that the expansion of cattle from the Near East and Anatolia into Europe does not appear to constitute a significant bottleneck, and that v) there is evidence for gene-flow between the Near Eastern/Anatolian and European cattle populations in the early phases of the European Neolithic, but that it is restricted after 5,000 BCE. The most plausible scenario to explain these results is a single and regionally restricted domestication process of cattle in the Near East with subsequent migration into Europe during the Neolithic transition without significant maternal interbreeding with the endogenous wild stock. Evidence for gene-flow between cattle populations from Southwestern Asia and Europe during the earlier phases of the European Neolithic points towards intercontinental trade connections between Neolithic farmers.

Amelie Scheu, Adam Powell, Ruth Bollongino, Jean-Denis Vigne, Anne Tresset, Canan Çakırlar, Norbert Benecke and Joachim Burger (2015)

BMC Genet 16: 54.

Pigmentation is a polygenic trait encompassing some of the most visible phenotypic variation observed in humans. Here we present direct estimates of selection acting on functional alleles in three key genes known to be involved in human pigmentation pathways – HERC2, SLC45A2, and TYR – using allele frequency estimates from Eneolithic, Bronze Age, and modern Eastern European samples and forward simulations. Neutrality was overwhelmingly rejected for all alleles studied, with point estimates of selection ranging from around 2–10% per generation. Our results provide direct evidence that strong selection favoring lighter skin, hair, and eye pigmentation has been operating in European populations over the last 5,000 y.

Sandra Wilde, Adrian Timpson, Karola Kirsanow, Elke Kaiser, Manfred Kayser, Martina Unterländer, Nina Hollfelder, Inna D. Potekhina, Wolfram Schier, Mark G. Thomas, and Joachim Burger (2014)

Proc Natl Acad Sci U S A 111(13): 4832-4837.

Debate on the ancestry of Europeans centers on the interplay between Mesolithic foragers and Neolithic farmers. Foragers are generally believed to have disappeared shortly after the arrival of agriculture. To investigate the relation between foragers and farmers, we examined Mesolithic and Neolithic samples from the Blätterhohle site. Mesolithic mitochondrial DNA sequences were typical of European foragers, whereas the Neolithic sample included additional lineages that are associated with early farmers. However, isotope analyses separate the Neolithic sample into two groups: one with an agriculturalist diet and one with a forager and freshwater fish diet, the latter carrying mitochondrial DNA sequences typical of Mesolithic hunter-gatherers. This indicates that the descendants of Mesolithic people maintained a foraging lifestyle in Central Europe for more than 2000 years after the arrival of farming societies.

Ruth Bollongino, Olaf Nehlich, Michael P. Richards, Jörg Orschiedt, Mark G. Thomas, Christian Sell, Zuzana Fajkošová, Adam Powell, Joachim Burger (2013)

Science 342(6157): 479-481.

The fundamental shift associated with the domestication of plants and animals allowed for a dramatic increase in human population sizes and the emergence of modern society. Despite its importance and the decades of research devoted to studying it, questions regarding the origins and processes of domestication remain. Here, we review recent theoretical advances and present a perspective that underscores the crucial role that population admixture has played in influencing the genomes of domestic animals over the past 10000 years. We then discuss novel approaches to generating and analysing genetic data, emphasising the importance of an explicit hypothesis-testing approach for the inference of the origins and subsequent evolution and demography of domestic animals. By applying next-generation sequencing technology alongside appropriate biostatistical methodologies, a substantially deeper understanding of domestication is on the horizon.

Greger Larson and Joachim Burger (2013)

Trends Genet 29(4): 197-205.

Lactase persistence, the ability to digest the milk sugar lactose in adulthood, is highly associated with a T allele situated 13,910 bp upstream from the actual lactase gene in Europeans. The frequency of this allele rose rapidly in Europe after transition from hunter-gatherer to agriculturalist lifestyles and the introduction of milkable domestic species from Anatolia some 8000 years ago. Here we first introduce the archaeological and historic background of early farming life in Europe, then summarize what is known of the physiological and genetic mechanisms of lactase persistence. Finally, we compile the evidence for a co-evolutionary process between dairying culture and lactase persistence. We describe the different hypotheses on how this allele spread over Europe and the main evolutionary forces shaping this process. We also summarize three different computer simulation approaches, which offer a means of developing a coherent and integrated understanding of the process of spread of lactase persistence and dairying.

Michela Leonardi, Pascale Gerbault, Mark G. Thomas, Joachim Burger (2012)

International Dairy Journal 22(2): 88-97.

After the domestication of animals and crops in the Near East some 11,000 years ago, farming had reached much of central Europe by 7500 years before the present. The extent to which these early European farmers were immigrants or descendants of resident hunter-gatherers who had adopted farming has been widely debated. We compared new mitochondrial DNA (mtDNA) sequences from late European hunter-gatherer skeletons with those from early farmers and from modern Europeans. We find large genetic differences between all three groups that cannot be explained by population continuity alone. Most (82%) of the ancient hunter-gatherers share mtDNA types that are relatively rare in central Europeans today. Together, these analyses provide persuasive evidence that the first farmers were not the descendants of local hunter-gatherers but immigrated into central Europe at the onset of the Neolithic.

Barbara Bramanti, Mark G. Thomas, Wolfgang Haak, Martina Unterländer, Pia Jores, Kristiina Tambets, Indre Antanaitis-Jacobs, Miriam N. Haidle, R. Jankauskas, Claus-Joachim Kind, Frank Lueth, Thomas Terberger, J. Hiller, S. Matsumura, Peter Forster, Joachim Burger (2009)

Science 326(5949): 137-140.

The extinct aurochs (Bos primigenius primigenius) was a large type of cattle that ranged over almost the whole Eurasian continent. The aurochs is the wild progenitor of modern cattle, but it is unclear whether European aurochs contributed to this process. To provide new insights into the demographic history of aurochs and domestic cattle, we have generated high-confidence mitochondrial DNA sequences from 59 archaeological skeletal finds, which were attributed to wild European cattle populations based on their chronological date and/or morphology. All pre-Neolithic aurochs belonged to the previously designated P haplogroup, indicating that this represents the Late Glacial Central European signature. We also report one new and highly divergent haplotype in a Neolithic aurochs sample from Germany, which points to greater variability during the Pleistocene. Furthermore, the Neolithic and Bronze Age samples that were classified with confidence as European aurochs using morphological criteria all carry P haplotype mitochondrial DNA, suggesting continuity of Late Glacial and Early Holocene aurochs populations in Europe. Bayesian analysis indicates that recent population growth gives a significantly better fit to our data than a constant-sized population, an observation consistent with a postglacial expansion scenario, possibly from a single European refugial population. Previous work has shown that most ancient and modern European domestic cattle carry haplotypes previously designated T. This, in combination with our new finding of a T haplotype in a very Early Neolithic site in Syria, lends persuasive support to a scenario whereby gracile Near Eastern domestic populations, carrying predominantly T haplotypes, replaced P haplotype-carrying robust autochthonous aurochs populations in Europe, from the Early Neolithic onward. During the period of coexistence, it appears that domestic cattle were kept separate from wild aurochs and introgression was extremely rare.

Ceiridwen J. Edwards, Ruth Bollongino, Amelie Scheu, Andrew Chamberlain, Anne Tresset, Jean-Denis Vigne, Jillian F. Baird, Greger Larson, Simon Y. W. Ho, Tim H. Heupink, Beth Shapiro, Abigail R. Freeman, Mark G. Thomas, Rose-Marie Arbogast, Betty Arndt, László Bartosiewicz, Norbert Benecke, Mihael Budja, Louis Chaix, Alice M. Choyke, Eric Coqueugniot, Hans-Jürgen Döhle, Holger Göldner, Sönke Hartz, Daniel Helmer, Barabara Herzig, Hitomi Hongo, Marjan Mashkour, Mehmet Özdogan, Erich Pucher, Georg Roth, Sabine Schade-Lindig, Ulrich Schmölcke, Rick J. Schulting, Elisabeth Stephan, Hans-Peter Uerpmann, István Vörös, Barbara Voytek, Daniel G. Bradley and Joachim Burger (2007)

Proceedings of the Royal Society B: Biological Sciences 274(1616): 1377-1385.

Lactase persistence (LP), the dominant Mendelian trait conferring the ability to digest the milk sugar lactose in adults, has risen to high frequency in central and northern Europeans in the last 20,000 years. This trait is likely to have conferred a selective advantage in individuals who consume appreciable amounts of unfermented milk. Some have argued for the “culture-historical hypothesis,” whereby LP alleles were rare until the advent of dairying early in the Neolithic but then rose rapidly in frequency under natural selection. Others favor the “reverse cause hypothesis,” whereby dairying was adopted in populations with preadaptive high LP allele frequencies. Analysis based on the conservation of lactase gene haplotypes indicates a recent origin and high selection coefficients for LP, although it has not been possible to say whether early Neolithic European populations were lactase persistent at appreciable frequencies. We developed a stepwise strategy for obtaining reliable nuclear ancient DNA from ancient skeletons, based on (i) the selection of skeletons from archaeological sites that showed excellent biomolecular preservation, (ii) obtaining highly reproducible human mitochondrial DNA sequences, and (iii) reliable short tandem repeat (STR) genotypes from the same specimens. By applying this experimental strategy, we have obtained high-confidence LP-associated genotypes from eight Neolithic and one Mesolithic human remains, using a range of strict criteria for ancient DNA work. We did not observe the allele most commonly associated with LP in Europeans, thus providing evidence for the culture-historical hypothesis, and indicating that LP was rare in early European farmers.

Joachim Burger, Martina Kirchner, Barbara Bramanti, Wolfgang Haak, Mark G. Thomas (2007)

Proceedings of the National Academy of Sciences of the United States of America 104(10): 3736-3741.

The ancestry of modern Europeans is a subject of debate among geneticists, archaeologists, and anthropologists. A crucial question is the extent to which Europeans are descended from the first European farmers in the Neolithic Age 7500 years ago or from Paleolithic hunter-gatherers who were present in Europe since 40,000 years ago. Here we present an analysis of ancient DNA from early European farmers. We successfully extracted and sequenced intact stretches of maternally inherited mitochondrial DNA (mtDNA) from 24 out of 57 Neolithic skeletons from various locations in Germany, Austria, and Hungary. We found that 25% of the Neolithic farmers had one characteristic mtDNA type and that this type formerly was widespread among Neolithic farmers in Central Europe. Europeans today have a 150-times lower frequency (0.2%) of this mtDNA type, revealing that these first Neolithic farmers did not have a strong genetic influence on modern European female lineages. Our finding lends weight to a proposed Paleolithic ancestry for modern Europeans.

Wolfgang Haak, Peter Forster, Barbara Bramanti, Shuichi Matsumura, Guido Brandt, Marc Tänzer, Richard Villems, Colin Renfrew, Detlef Gronenborn, Kurt W. Alt, Joachim Burger (2005)

Science 310(5750): 1016-1018.

To reconstruct the phylogenetic position of the extinct cave lion (Panthera leo spelaea), we sequenced 1 kb of the mitochondrial cytochrome b gene from two Pleistocene cave lion DNA samples (47 and 32 ky B.P.). Phylogenetic analysis shows that the ancient sequences form a clade that is most closely related to the extant lions from Africa and Asia; at the same time, cave lions appear to be highly distinct from their living relatives. Our data show that these cave lion sequences represent lineages that were isolated from lions in Africa and Asia since their dispersal over Europe about 600 ky B.P., as they are not found among our sample of extant populations. The cave lion lineages presented here went extinct without mitochondrial descendants on other continents. The high sequence divergence in the cytochrome b gene between cave and modern lions is notable.

Joachim Burger, Wilfried Rosendahl, Odile Loreille, Helmut Hemmer, Torsten Eriksson, Anders Götherström, Jennifer Hiller, Matthew J. Collins, Timothy Wess, Kurt W. Alt (2004)

Molecular Phylogenetics and Evolution 30(3): 841-849.