What’s Sardinia got to do with it? Ancient and modern genomes shed light on the genetic structure of Europe.

Blog author Yuan Zhu is a graduate student in Dmitri Petrov's lab

Blog author Yuan Zhu, formerly a PhD student in the Petrov lab, is now a Research Fellow at the Genome Institute of Singapore.

The Neolithic Revolution is the oldest documented agricultural revolution in human history. More than just the domestication of certain crops and animals, it describes a critical time in human history when hunter-gatherer groups transitioned into sedentary farming communities. This drastic change in lifestyle led to a major shift in living conditions and cultural practices, setting up the necessary prerequisites to support the kind of population density eventually possible in modern society.

In Central Europe, the Neolithic Revolution is thought to have taken place around 8,000-4,000 BC. Historians have long wondered about how farming was introduced and spread across the continents. Was the new practice brought in as novel ideas incorporated by local communities? Did new immigrants bring their lifestyle with them, possibly outcompeting existing hunter-gatherers and eventually displacing them all together? Was it perhaps even more complicated? What happened after?

What Ötzi can tell us

Ancient human remains from around the time of the revolution can yield some insight. Ötzi the Tyrolean Iceman, a 5,300-year-old natural mummy found frozen in the Alps on the border of Italy and Austria, was recently shown (by a group that included CEHG researchers Martin Sikora and Carlos Bustamante) to belong to a Y-chromosome lineage mostly found in contemporary Sardinia [1]. This was surprising information. The Iceman’s life was spent in a narrow range within 60 km of his site of discovery [2]. He was unequivocally local, and clearly a farmer. Yet his lineage has since disappeared from Central Europe, suggesting that demographic scenarios were more complex than expected, and that at some point this Sardinian-like ancestry may have spanned Neolithic Europe.

A). The location of the discovery sites of ancient individuals studied, with hunter-gatherers (HG) represented as circles, and farming (F) individuals represented as squares. B). ADMIXTURE results of modern populations on the left panel, and inferred genetic composition of ancient individuals on the right. [Adapted from Figure 1, Sikora et al. 2014.]

A). The location of the discovery sites of ancient individuals studied, with hunter-gatherers (HG) represented as circles, and farming (F) individuals represented as squares. B). ADMIXTURE results of modern populations on the left panel, and inferred genetic composition of ancient individuals on the right. [Adapted from Figure 1, Sikora et al. 2014.]

Sardinia: a genetic snapshot of the Neolithic?

In a recent paper published in PLOS Genetics, Sikora and colleagues sought to address this hypothesis by making full use of recent advancements in the sequencing of nuclear ancient DNA [3]. However, the Iceman alone was not sufficient to represent a continent. Ancient DNA sequences from six individuals from across Europe, including both farmer and hunter-gatherer individuals, were analyzed by the authors in order to paint a clearer picture of the demographics of Neolithic Europe. Two of the farmers were found in Bulgaria and were previously sequenced using an ancient DNA capture method developed by Sikora’s colleague in the Bustamante lab, Meredith Carpenter [4, and see blog post here]. In addition, Sikora made use of contemporary population SNP data, including sequence data from over 400 modern Sardinians, to provide a solid reference from which to estimate the true genetic affiliation of these ancient humans.

Some of the most interesting results from the analysis came from contrasts between the farmers (Iceman, gok4, and P192-1), the hunter-gatherers (ajv7 and brana1), and modern-day European populations. When the authors applied the clustering algorithm ADMIXTURE to the data, they found that the farmer individuals had significant portions of shared ancestry with modern Sardinians (Southern Europe), a characteristic largely absent in the HG individuals, who showed mainly Northern European (Basque) and Russian affiliated ancestry. Principal component analysis (PCA) and a statistic called the D-test agreed with high confidence—hunter-gatherers looked more Northern European, whereas farmers seemed more Sardinian than any other European group tested. TreeMix, a program that models population splits while allowing for admixture between branches, provided a similar answer when applied to the data from 1000 Genomes and the modern Sardinians, and further suggested a possible admixture scenario involving at least three major events, all of which falls neatly in line with previous work.

Taken together, the data support the authors’ original hypothesis—Sardinian-like ancestry was probably once common in Neolithic Europe. The Iceman, gok4, and P192-1 were discovered in very different locations, and P192-1 in particular was 2,000 years younger than the others, making it even more unlikely that all three were recurrent immigrants from Sardinia (which was thought to be uninhabited by hunter-gatherers prior to the Neolithic), and further suggesting that the lineage may have persisted for a while on the continent. In fact, Sikora and colleagues propose that Sardinia is a “modern-day ‘snapshot’ of the genetic structure of the people associated with the spread of agriculture in Europe.”

A proposed, highly simplified version of recent European demographic history. A). Early hunter-gatherers (closest to modern day Russian/Basque) were B). heavily influenced by an influx of farmers C) who spread across all of Europe and into Sardinia D). and subsequently maintained only in Sardinia due to genetic isolation. [Adapted from Figure 4, Sikora et al. 2014]

A proposed, highly simplified version of recent European demographic history. A). Early hunter-gatherers (closest to modern day Russian/Basque) were B). heavily influenced by an influx of farmers C) who spread across all of Europe and into Sardinia D). and subsequently maintained only in Sardinia due to genetic isolation. [Adapted from Figure 4, Sikora et al. 2014]

Bridging the past and the future with ancient DNA

From here, the story is far from over. In fact, it only gets more complicated, and more work remains to be done. While a simplified model was proposed, the authors note that multiple sources of evidence suggest a far more complex and nuanced recent demographic history for Europe that we have yet to untangle. There are issues with ancient DNA sequences, such as characteristic DNA damage patterns, that are unique to the nature of the data. Potential issues with current methods being unable to handle such underlying patterns forced the authors to analyze every ancient DNA sample against modern populations individually. As with every advance in sequencing technology, with ancient DNA sequencing getting more accurate and accessible, new analytical methods must be developed to take full advantage of the data.

References

[1] Keller A, Graefen A, Ball M, Matzas M, Boisguerin V, et al. (2012) New insights into the Tyrolean Iceman’s origin and phenotype as inferred by whole-genome sequencing. Nature Communications 3: 698.
[2] Müller W, Fricke H, Halliday AN, McCulloch MT, Wartho J-A (2003) Origin and Migration of the Alpine Iceman. Science 302: 862–866. doi: 10.1126/science.1089837
[3] Sikora M, Carpenter ML, Moreno-Estrada A, Henn BM, Underhill PA, et al. (2014) Population Genomic Analysis of Ancient and Modern Genomes Yields New Insights into the Genetic Ancestry of the Tyrolean Iceman and the Genetic Structure of Europe. PLOS Genetics, DOI:10.1371/journal.pgen.1004353
[4] Carpenter, ML, Buenrostro, JD, Valdiosera, C, Schroeder, H, Allentoft, ME, Sikora, M, Rasmussen, M, et al. (2013). Pulling out the 1%: Whole-Genome Capture for the Targeted Enrichment of Ancient DNA Sequencing Libraries. Am J Hum Genet. 2013 Nov 7;93(5):852-64. doi: 10.1016/j.ajhg.2013.10.002.

Paper author: Martin Sikora was a postdoc in Carlos Bustamante's lab. He is now a group leader at the Centre for GeoGenetics in Copenhagen, Denmark.

Paper author Martin Sikora was a postdoctoral fellow in Carlos Bustamante’s lab. He is now a group leader at the Center for GeoGenetics in Copenhagen, Denmark.

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