• Welcome!

    The Palaeogenetics Group Mainz performs research on the genetic population history of humans and their domestic animals. A particular focus lies on the Neolithic period when humans became sedentary in the Near East, Anatolia and Europe some 7,000-10,000 years ago.

    To learn more about humans of the past, we extract DNA from archaeological skeletons and sequence their genomes. Then we use biostatistic and population genetic approaches to infer their evolutionary and demographic history.

  • Welcome!

    The Palaeogenetics Group Mainz performs research on the genetic population history of humans and their domestic animals. A particular focus lies on the Neolithic period when humans became sedentary in the Near East, Anatolia and Europe some 7,000-10,000 years ago.

    To learn more about humans of the past, we extract DNA from archaeological skeletons and sequence their genomes. Then we use biostatistic and population genetic approaches to infer their evolutionary and demographic history.

  • Welcome!

    The Palaeogenetics Group Mainz performs research on the genetic population history of humans and their domestic animals. A particular focus lies on the Neolithic period when humans became sedentary in the Near East, Anatolia and Europe some 7,000-10,000 years ago.

    To learn more about humans of the past, we extract DNA from archaeological skeletons and sequence their genomes. Then we use biostatistic and population genetic approaches to infer their evolutionary and demographic history.

  • Welcome!

    The Palaeogenetics Group Mainz performs research on the genetic population history of humans and their domestic animals. A particular focus lies on the Neolithic period when humans became sedentary in the Near East, Anatolia and Europe some 7,000-10,000 years ago.

    To learn more about humans of the past, we extract DNA from archaeological skeletons and sequence their genomes. Then we use biostatistic and population genetic approaches to infer their evolutionary and demographic history.


Ancestry and demography and descendants of Iron Age nomads of the Eurasian Steppe

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

Neolithic animal domestication as seen from ancient DNA

In recent years, archaeological, archaeozoological and population genetic studies have increasingly converged on a southwest Asian origin for the four Neolithic farm animals: cattle, sheep, goats, and pigs. The power of ancient DNA studies lies in the possibility of tracking the genetic traces of major demographic processes, such as domestication itself and subsequent migration, at their spatiotemporal sources. In doing so, they are bypassing more recent events, which may have blurred ancient signals until the point of disappearance. Past ancient DNA studies have mostly relied on a single, powerful and e even for degraded ancient samples e easily accessible genetic marker: the maternally inherited mitochondrial DNA (mtDNA). For example, mtDNA studies have allowed for a correlation of genetic diversity patterns with Neolithic expansion routes and to infer ancestral population sizes at the domestication origin for cattle, and to detect evidence for hybridisation between imported domesticated and local wild populations in pigs. However, novel technologies that enable high-throughput sequencing of entire genomes have revolutionised the field of ancient DNA research. The continuously growing field of palaeogenomics is now able to address detailed questions about past population dynamics, including the complex history of population admixture and selection. This article will outline the potential of ancient DNA data gained from traditional and high-throughput sequencing technologies, and how they contribute to present and future domestication research.

Amelie Scheu (2017)

in press: Quaternary International (2017), http://dx.doi.org/10.1016/j.quaint.2017.02.009

ATLAS: Analysis Tools for Low-depth and Ancient Samples

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

Early cave art and ancient DNA record the origin of European bison

The two living species of bison (European and American) are among the few terrestrial megafauna to have survived the late Pleistocene extinctions. Despite the extensive bovid fossil record in Eurasia, the evolutionary history of the European bison (or wisent, Bison bonasus) before the Holocene (<11.7 thousand years ago (kya)) remains a mystery. We use complete ancient mitochondrial genomes and genome-wide nuclear DNA surveys to reveal that the wisent is the product of hybridization between the extinct steppe bison (Bison priscus) and ancestors of modern cattle (aurochs, Bos primigenius) before 120 kya, and contains up to 10% aurochs genomic ancestry. Although undetected within the fossil record, ancestors of the wisent have alternated ecological dominance with steppe bison in association with major environmental shifts since at least 55 kya. Early cave artists recorded distinct morphological forms consistent with these replacement events, around the Last Glacial Maximum (LGM, ~21–18 kya).

Julien Soubrier, Graham Gower, Kefei Chen, Stephen M. Richards, Bastien Llamas , Kieren J. Mitchell, Simon Y.W. Ho, Pavel Kosintsev, Michael S.Y. Lee, Gennady Baryshnikov, Ruth Bollongino, Pere Bover, Joachim Burger, David Chivall, Evelyne Crégut-Bonnoure, Jared E. Decker, Vladimir B. Doronichev, Katerina Douka, Damien A. Fordham, Federica Fontana, Carole Fritz, Jan Glimmerveen, Liubov V. Golovanova, Colin Groves, Antonio Guerreschi, Wolfgang Haak, Tom Higham, Emilia Hofman-Kamińska, Alexander Immel, Marie-Anne Julien, Johannes Krause, Oleksandra Krotova, Frauke Langbein, Greger Larson, Adam Rohrlach, Amelie Scheu, Robert D. Schnabel, Jeremy F. Taylor, Małgorzata Tokarska, Gilles Tosello, Johannes van der Plicht, Ayla van Loenen, Jean-Denis Vigne, Oliver Wooley, Ludovic Orlando, Rafał Kowalczyk, Beth Shapiro & Alan Cooper (2016)

Nat. Commun. 7, 13158 doi: 10.1038/ncomms13158

Inferring heterozygosity from ancient and low coverage genomes

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)

Ancient European dog genomes reveal continuity since the early Neolithic

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. We sequenced the whole genomes of an Early and End Neolithic dog from Germany, including a sample associated with one of Europe’s earliest farming communities. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a Late Neolithic population replacement previously suggested by analysis of mitochondrial DNA and a Late Neolithic Irish genome. However, our End Neolithic sample possesses additional ancestry found in modern Indian dogs, which we speculate may be derived from dogs that accompanied humans from the Eastern European steppe migrating into Central Europe. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication to 20,000-40,000 years ago. Interestingly, the extreme copy number expansion of the AMY2B gene found in modern dogs was not observed in the ancient samples, indicating that the AMY2B copy number increase arose as an adaptation to starch-rich diets after the advent of agriculture in the Neolithic period.

Laura Botigue, Shiya Song, Amelie Scheu, Shyamalika Gopalan, Amanda Pendleton, Matthew Oetjens, Angela Taravella, Timo Seregély, Andrea Zeeb-Lanz, Rose-Marie Arbogast, Dean Bobo, Kevin Daly, Martina Unterländer, Joachim Burger, Jeffrey Kidd, Krishna R Veeramah (2016)

bioRxiv, https://doi.org/10.1101/068189

Early Neolithic genomes from the eastern Fertile Crescent

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.




Full text 

Early farmers from across Europe directly descended from Neolithic Aegeans

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.

The genetic prehistory of domesticated cattle from their origin to the spread across Europe

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.

Ancient proteins resolve the evolutionary history of Darwin’s South American ungulates

No large group of recently extinct placental mammals remains as evolutionarily cryptic as the approximately 280 genera grouped as ‘South American native ungulates’. To Charles Darwin, who first collected their remains, they included perhaps the ‘strangest animal[s] ever discovered’. Today, much like 180 years ago, it is no clearer whether they had one origin or several, arose before or after the Cretaceous/Palaeogene transition 66.2 million years ago, or are more likely to belong with the elephants and sirenians of superorder Afrotheria than with the euungulates (cattle, horses, and allies) of superorder Laurasiatheria. Morphology-based analyses have proved unconvincing because convergences are pervasive among unrelated ungulate-like placentals. Approaches using ancient DNA have also been unsuccessful, probably because of rapid DNA degradation in semitropical and temperate deposits. Here we apply proteomic analysis to screen bone samples of the Late Quaternary South American native ungulate taxa Toxodon (Notoungulata) and Macrauchenia (Litopterna) for phylogenetically informative protein sequences. For each ungulate, we obtain approximately 90% direct sequence coverage of type I collagen alpha1- and alpha2-chains, representing approximately 900 of 1,140 amino-acid residues for each subunit. A phylogeny is estimated from an alignment of these fossil sequences with collagen (I) gene transcripts from available mammalian genomes or mass spectrometrically derived sequence data obtained for this study. The resulting consensus tree agrees well with recent higher-level mammalian phylogenies. Toxodon and Macrauchenia form a monophyletic group whose sister taxon is not Afrotheria or any of its constituent clades as recently claimed, but instead crown Perissodactyla (horses, tapirs, and rhinoceroses). These results are consistent with the origin of at least some South American native ungulates from ‘condylarths’, a paraphyletic assembly of archaic placentals. With ongoing improvements in instrumentation and analytical procedures, proteomics may produce a revolution in systematics such as that achieved by genomics, but with the possibility of reaching much further back in time.

Frido Welker, Matthew J. Collins, Jessica A. Thomas, Marc Wadsley, Selina Brace, Enrico Cappellini, Samuel T. Turvey, Marcelo Reguero, Javier N. Gelfo, Alejandro Kramarz, Joachim Burger, Jane Thomas-Oates, David A. Ashford, Peter D. Ashton, Keri Rowsell, Duncan M. Porter, Benedikt Kessler, Roman Fischer, Carsten Baessmann, Stephanie Kaspar, Jesper V. Olsen, Patrick Kiley, James A. Elliott, Christian D. Kelstrup, Victoria Mullin, Michael Hofreiter, Eske Willerslev, Jean-Jacques Hublin, Ludovic Orlando, Ian Barnes, Ross D. E. MacPhee (2015)

Nature 522(7554): 81-84.

Ancient human genomes suggest three ancestral populations for present-day Europeans

We sequenced the genomes of an approximately 7,000-year-old farmer from Germany and eight approximately 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations’ deep relationships and show that early European farmers had approximately 44% ancestry from a ‘basal Eurasian’ population that split before the diversification of other non-African lineages.

Iosif Lazaridis, Nick Patterson, Alissa Mittnik, Gabriel Renaud, Swapan Mallick, Karola Kirsanow, Peter H. Sudmant, Joshua G. Schraiber, Sergi Castellano, Mark Lipson, Bonnie Berger, Christos Economou, Ruth Bollongino, Qiaomei Fu, Kirsten I. Bos, Susanne Nordenfelt, Heng Li, Cesare de Filippo, Kay Prüfer, Susanna Sawyer, Cosimo Posth, Wolfgang Haak, Fredrik Hallgren, Elin Fornander, Nadin Rohland, Dominique Delsate, Michael Francken, Jean-Michel Guinet, Joachim Wahl, George Ayodo, Hamza A. Babiker, Graciela Bailliet, Elena Balanovska, Oleg Balanovsky, Ramiro Barrantes, Gabriel Bedoya, Haim Ben-Ami, Judit Bene, Fouad Berrada, Claudio M. Bravi, Francesca Brisighelli, George B. J. Busby, Francesco Cali, Mikhail Churnosov, David E. C. Cole, Daniel Corach, Larissa Damba, George van Driem, Stanislav Dryomov, Jean-Michel Dugoujon, Sardana A. Fedorova, Irene Gallego Romero, Marina Gubina, Michael Hammer, Brenna M. Henn, Tor Hervig, Ugur Hodoglugil, Aashish R. Jha, Sena Karachanak-Yankova, Rita Khusainova, Elza Khusnutdinova, Rick Kittles, Toomas Kivisild, William Klitz, Vaidutis Kučinskas, Alena Kushniarevich, Leila Laredj, Sergey Litvinov, Theologos Loukidis, Robert W. Mahley, Be’la Melegh, Ene Metspalu, Julio Molina, Joanna Mountain, Klemetti Nakkalajarvi, Desislava Nesheva, Thomas Nyambo, Ludmila Osipova, Juri Parik, Fedor Platonov, Olga Posukh, Valentino Romano, Francisco Rothhammer, Igor Rudan, Ruslan Ruizbakiev, Hovhannes Sahakyan, Antti Sajantila, Antonio Salas, Elena B. Starikovskaya, Ayele Tarekegn, Draga Toncheva, Shahlo Turdikulova, Ingrida Uktveryte, Olga Utevska, René Vasquez, Mercedes Villena, Mikhail Voevoda, Cheryl A. Winkler, Levon Yepiskoposyan, Pierre Zalloua, Tatijana Zemunik, Alan Cooper, Cristian Capelli, Mark G.Thomas, Andres Ruiz-Linares, Sarah A. Tishkoff, Lalji Singh, Kumarasamy Thangaraj, Richard Villems, David Comas, Rem Sukernik, Mait Metspalu, Matthias Meyer, Evan E. Eichler, Joachim Burger, Montgomery Slatkin, Svante Pääbo, Janet Kelso, David Reich, Johannes Krause (2014)

Nature 513(7518): 409-413.

Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y

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.

2000 Years of Parallel Societies in Stone Age Central Europe

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.

A population genetics view of animal domestication

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.

The evolution of lactase persistence in Europe. A synthesis of archaeological and genetic evidence

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.

AIP Mutation in Pituitary Adenomas in the 18th Century and Today

Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patient’s teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier.

Harvinder S. Chahal, Karen Stals, Martina Unterländer, David J. Balding, Mark G. Thomas, Ajith V. Kumar, G. Michael Besser, A. Brew Atkinson, Patrick J. Morrison, Trevor A. Howlett, Miles J. Levy, Steve M. Orme, Scott A. Akker, Richard L. Abel, Ashley B. Grossman, Joachim Burger, Sian Ellard, Márta Korbonits (2011)

The New England journal of medicine 364(1): 43-50.

Genetic Discontinuity Between Local Hunter-Gatherers and Central Europe’s First Farmers

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 Origins of Lactase Persistence in Europe

Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (–13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the –13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia’s geographic space. Using data on –13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the –13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe.

Yuval Itan, Adam Powell, Mark A. Beaumont, Joachim Burger, Mark G. Thomas (2009)

PLoS Comput Biol 5(8): e1000491.

Mitochondrial DNA analysis shows a Near Eastern Neolithic origin for domestic cattle and no indication of domestication of European aurochs

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.

Absence of the lactase-persistence-associated allele in early Neolithic Europeans

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.

Early history of European domestic cattle as revealed by ancient DNA

We present an extensive ancient DNA analysis of mainly Neolithic cattle bones sampled from archaeological sites along the route of Neolithic expansion, from Turkey to North-Central Europe and Britain. We place this first reasonable population sample of Neolithic cattle mitochondrial DNA sequence diversity in context to illustrate the continuity of haplotype variation patterns from the first European domestic cattle to the present. Interestingly, the dominant Central European pattern, a starburst phylogeny around the modal sequence, T3, has a Neolithic origin, and the reduced diversity within this cluster in the ancient samples accords with their shorter history of post-domestic accumulation of mutation.

Ruth Bollongino, Ceiridwen J. Edwards, Kurt W. Alt, Joachim Burger, Daniel G. Bradley (2006)

Biology Letters 2(1): 155-159.

Ancient DNA from the First European Farmers in 7500-Year-Old Neolithic Sites

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.

Molecular phylogeny of the extinct cave lion Panthera leo spelaea

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.