Parental relatedness through time revealed by runs of homozygosity in ancient DNA

Parental relatedness of present-day humans varies substantially across the globe, but little is known about the past. Here we analyze ancient DNA, leveraging that parental relatedness leaves genomic traces in the form of runs of homozygosity. We present an approach to identify such runs in low-coverage ancient DNA data aided by haplotype information from a modern phased reference panel. Simulation and experiments show that this method robustly detects runs of homozygosity longer than 4 centimorgan for ancient individuals with at least 0.3 × coverage. Analyzing genomic data from 1,785 ancient humans who lived in the last 45,000 years, we detect low rates of first cousin or closer unions across most ancient populations. Moreover, we find a marked decay in background parental relatedness co-occurring with or shortly after the advent of sedentary agriculture. We observe this signal, likely linked to increasing local population sizes, across several geographic transects worldwide

Surfing waves of data in San Diego: Sophisticated analyses provide a broad view of human genetic diversity

A report on the 64th annual American Society of Human Genetics meeting held in San Diego, USA, 18-22 October, 2014

Population history from the Neolithic to present on the Mediterranean island of Sardinia: an ancient DNA perspective

Recent ancient DNA studies of western Eurasia have revealed a dynamic history of admixture, with evidence for major migrations during the Neolithic and Bronze Age. The population of the Mediterranean island of Sardinia has been notable in these studies –} Neolithic individuals from mainland Europe cluster more closely with Sardinian individuals than with all other present-day Europeans. The current model to explain this result is that Sardinia received an initial influx of Neolithic ancestry and then remained relatively isolated from expansions in the later Neolithic and Bronze Age that took place in continental Europe. To test this model, we generated genome-wide capture data (approximately 1.2 million variants) for 43 ancient Sardinian individuals spanning the Neolithic through the Bronze Age, including individuals from Sardinia{’}s Nuragic culture, which is known for the construction of numerous large stone towers throughout the island. We analyze these new samples in the context of previously generated genome-wide ancient DNA data from 972 ancient individuals across western Eurasia and whole-genome sequence data from approximately 1,500 modern individuals from Sardinia. The ancient Sardinian individuals show a strong affinity to western Mediterranean Neolithic populations and we infer a high degree of genetic continuity on the island from the Neolithic (around fifth millennium BCE) through the Nuragic period (second millennium BCE). In particular, during the Bronze Age in Sardinia, we do not find significant levels of the {“}Steppe{” ancestry that was spreading in many other parts of Europe at that time. We also characterize subsequent genetic influx between the Nuragic period and the present. We detect novel, modest signals of admixture between 1,000 BCE and present-day, from ancestry sources in the eastern and northern Mediterranean. Within Sardinia, we confirm that populations from the more geographically isolated mountainous provinces have experienced elevated levels of genetic drift and that northern and southwestern regions of the island received more gene flow from outside Sardinia. Overall, our genetic analysis sheds new light on the origin of Neolithic settlement on Sardinia, reinforces models of genetic continuity on the island, and provides enhanced power to detect post-Bronze-Age gene flow. Together, these findings offer a refined demographic model for future medical genetic studies in Sardinia

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Inference of population splits and mixtures from genome-wide allele frequency data

Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In this model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication, and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and "ancient" Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.comComment: 28 pages, 6 figures in main text. Attached supplement is 22 pages, 15 figures. This is an updated version of the preprint available at http://precedings.nature.com/documents/6956/version/

A Genealogical Interpretation of Principal Components Analysis

Principal components analysis, PCA, is a statistical method commonly used in population genetics to identify structure in the distribution of genetic variation across geographical location and ethnic background. However, while the method is often used to inform about historical demographic processes, little is known about the relationship between fundamental demographic parameters and the projection of samples onto the primary axes. Here I show that for SNP data the projection of samples onto the principal components can be obtained directly from considering the average coalescent times between pairs of haploid genomes. The result provides a framework for interpreting PCA projections in terms of underlying processes, including migration, geographical isolation, and admixture. I also demonstrate a link between PCA and Wright's fst and show that SNP ascertainment has a largely simple and predictable effect on the projection of samples. Using examples from human genetics, I discuss the application of these results to empirical data and the implications for inference

A Longitudinal Cline Characterizes the Genetic Structure of Human Populations in the Tibetan Plateau

Indigenous populations of the Tibetan plateau have attracted much attention for their good performance at extreme high altitude. Most genetic studies of Tibetan adaptations have used genetic variation data at the genome scale, while genetic inferences about their de- mography and population structure are largely based on uniparental markers. To provide genome-wide information on population structure, we analyzed new and published data of 338 individuals from indigenous populations across the plateau in conjunction with world- wide genetic variation data. We found a clear signal of genetic stratification across the east- west axis within Tibetan samples. Samples from more eastern locations tend to have higher genetic affinity with lowland East Asians, which can be explained by more gene flow from lowland East Asia onto the plateau. Our findings corroborate a previous report of admixture signals in Tibetans, which were based on a subset of the samples analyzed here, but add evidence for isolation by distance in a broader geospatial context

Iron Age and Anglo-Saxon genomes from East England reveal British migration history

British population history has been shaped by a series of immigrations, including the early Anglo-Saxon migrations after 400 CE. It remains an open question how these events affected the genetic composition of the current British population. Here, we present whole-genome sequences from 10 individuals excavated close to Cambridge in the East of England, ranging from the late Iron Age to the middle Anglo-Saxon period. By analysing shared rare variants with hundreds of modern samples from Britain and Europe, we estimate that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations. We gain further insight with a new method, rarecoal, which infers population history and identifies fine-scale genetic ancestry from rare variants. Using rarecoal we find that the Anglo-Saxon samples are closely related to modern Dutch and Danish populations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain

Chemical characterization of the stained glass window from the rose window, Siena Duomo (Italy, 1288-1289)

[EN] The chemical composition of nine medieval coloured stained glasses from Duomo (Catedral) of Siena, Italy, has been characterized. They come from the rose window elaborated under the drawing of Duccio di Buoninsegna masterwork (1288- 89 AD). This note explains the results obtained by EMPA, representative of bulk chemistry of several coloured glasses (deep green, olive green, yellow, purple, pink, deep blue, light blue, red plaqué and also uncoloured), as well as the associated trace elements (obtained by Induced Coupled Plasma Mass Spectrometry) that represent the chemical fingerprint of these glasses. The studied samples are sodium-calcium glass (chemical compositions in the range 13-14 wt% Na2O, 56-64 wt% SiO2, 4 wt% MgO, 9-10 wt% CaO, 2,5-4 wt% K2O); thus of Mediterranean tradition.This fact has been found by our team in previous studies (stained glasses from the church of Monestir de Pedralbes, Barcelona) for XIV century glass made at least 40 years later. As a general rule, the conservation state of these sodium glasses is good, except for the cohesion of grisaille to glass mesostase. This study allowed to identify three glass groups developed from different raw material formulations: a first group is constituted by deep green, olive green, light blue and yellow glass; a second one comprises by uncoloured, deep purple, deep blue and pink glass; and finally, the plaqué red glass that shows deeply different composition. Pink and yellow glass was produced following the traditional recipe compiled by Theophilus, a monk who lived at the beginning of XII century. This implies a separate process of raw material purification and a careful control of the redox kiln conditions; thus, these glasses can be considered as traditional or technologically not evolved. The deep blue, light blue and deep purple were obtained after the artisan dosed addition of a cobalt salt. Olive green and deep green glasses were produced with addition of copper (together with manganese and iron), previously prepared as a pigment that has as excipient a potassium glass. The use of potassium glass instead of the sodium glass locally produced strongly suggests that the pigment could be bought directly from Middle or Northern Europe markets and/or could be a sub-product of copper ore melting. On the other hand, the production of sodium red ruby plaqué glass, technologically more evolved and comparable to the coeval potassium glass coming from the Central Europe glass factories, would be outstanding in the XIV century; but we interpret (taking into account its chemical composition) that was produced later and introduced during the restoration conducted at the end of XVII century. We can also note the use of well-dosed lead additions in order to increase the lightness and transparency of coloured glass. Manganese has been a very important element in the Siena workshop glassmaker colour palette achievements. On the other hand, the trace-element chemical fingerprint of the glass allows arguing what kind of mineral salts were used as pigments, as well as the way to introduce it in the uncoloured original glass.[ES] Se han caracterizado químicamente una colección de vidrios arquitectónicos coloreados originales del rosetón del Duomo (catedral) de Siena, Italia, realizados bajo diseño del artista Duccio di Buoninsegna en 1288-89. Esta comunicación expone los resultados obtenidos mediante el empleo de microsonda electrónica de Castaing (mayoritarios) y espectrometría de masas con fuente de plasma acoplado inductivamente (ICP-MS, elementos en traza) en vidrios de varios colores (incoloro, verde oscuro, verde oliva, amarillo, violeta, rosa, azul oscuro, azul celeste, rojo plaqué). Se trata de vidrios sódico-cálcicos (valores en peso alrededor del 13-14 % de Na2O, 56-64 % SiO2, 4% MgO, 9-10 % CaO, 2,5-4 K2O) de tradición por tanto mediterránea. Un resultado semejante se encontró precedentemente para vidrios realizados a lo largo del siglo XIV, cuanto menos unos 40 años después (vidriera de la iglesia del Monestir de Pedralbes, Barcelona). En general, el estado de conservación de estos vidrios es bueno, excepto por lo que se refiere a la adherencia de las grisallas al vidrio base. El estudio desarrollado ha permitido identificar tres grupos de vidrios desarrollados a partir de formulaciones de diferentes composiciones: un primer grupo constituido por los vidrios de color verde claro, verde oscuro, azul celeste y amarillo; un segundo grupo constituido por los vidrios incoloro, violeta, azul oscuro, y malva; y finalmente el vidrio rojo plaqué, de composición netamente diferente a todos los demás. Desde el punto de vista de la obtención de los colores, cabe destacar que los datos químicos permiten deducir que el malva y el amarillo han sido elaborados siguiendo la receta tradicional del monje Theophilus de inicios del siglo XII, utilizando un proceso de purificación especial de las materias primas, y controlando artesanalmente las condiciones redox del horno; en este sentido, estos vidrios se pueden calificar como tradicionales o tecnológicamente poco evolucionados. Los colores azul oscuro, violeta y azul celeste se han obtenido mediante la adición de una misma sal de cobalto en diferentes dosis, y los colores verde oliva y verde oscuro mediante la adición de cobre (junto con manganeso y hierro), previamente preparados en un colorante que tiene como excipiente un vidrio potásico. Este último hecho (el empleo de vidrio potásico no usual en los centros productores del área mediterránea) permite suponer que el color puede haber sido comprado directamente a un fabricante centroeuropeo o que se tratara de un subproducto de fundición de minerales de cobre. Por su parte, la fabricación del vidrio plaqué, tecnológicamente más complejo y comparable al vidrio rojo plaqué potásico centroeuropeo contemporáneo indicaría, si fuera original, la incorporación de este proceso tecnológico al taller local. En opinión de los autores se trata de un vidrio de producción local mucho más tardia, incorporado en la restauración documentada a finales del siglo XVII. Destaca también, como en Pedralbes, el empleo del plomo para aumentar la luminosidad y transparencia del vidrio, en dosis variables atendiendo al color del vidrio. Por otro lado hay que señalar que en Siena el manganeso es un elemento muy importante con el que el fabricante del vidrio jugó intensamente para obtener la paleta de colores. El análisis de los metales presentes como elementos traza, y de las tierras raras, permite establecer sólidas hipótesis sobre el tipo de sales minerales empleadas como colorantes y como fueron incorporados al vidrio incoloro original.Este trabajo se ha podido realizar en el marco de diferentes proyectos financiados (proyecto 3338 de la Fundació Bosch i Gimpera, UB; acción integrada hispano-italiana HI2006-0190: La producción y el comercio del vidrio plano en Europa y en el Mediterráneo Occidental, entre los siglos XI y XV: un estudio arqueométrico) . La caracterización geoquímica de los vidrios mediante MSE e ICP-MS se ha llevado a cabo en los Serveis Científico-Tècnics de la Universitat de Barcelona (SCT-UB);Peer reviewe

Live Attenuated Rev-Independent Nef¯SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques

Background: Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef¯ simian immunodeficiency virus (Rev-Ind Nef¯SIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges. Methodology/Principal Findings Three groups of four RM were inoculated with Rev-Ind Nef¯SIV and compared. Group 1 was inoculated 8 years prior and again 15 months before low dose intrarectal challenges with SIVsmE660. Group 2 animals were inoculated with Rev-Ind Nef¯SIV at 15 months and Group 3 at 2 weeks prior to the SIVsmE660 challenges, respectively. Group 4 served as unvaccinated controls. All RMs underwent repeated weekly low-dose intrarectal challenges with SIVsmE660. Surprisingly, all RMs with acute live-attenuated virus infection (Group 3) became superinfected with the challenge virus, in contrast to the two other vaccine groups (Groups 1 and 2) (P=0.006 for each) and controls (Group 4) (P=0.022). Gene expression analysis showed significant upregulation of innate immune response-related chemokines and their receptors, most notably CCR5 in Group 3 animals during acute infection with Rev-Ind Nef¯SIV. Conclusions/Significance: We conclude that although Rev-Ind Nef¯SIV remained apathogenic, acute replication of the vaccine strain was not protective but associated with increased acquisition of heterologous mucosal SIVsmE660 challenges