Biology subjects

Saag, L.

Publications and source records attributed to Saag, L..

9 recordsLinked to original sources

bioRxiv2024

2500 Years of Human Betaherpesvirus 6A and 6B Evolution Revealed by Ancient DNA

Human betaherpesviruses 6A and 6B are double-stranded DNA viruses, specialised in infecting humans and are best known as the main causative pathogens of the common childhood infection "sixth disease". Despite only being discovered in the 1980s, these viruses are speculated to have a much longer and more complex history within the human population than available modern data make clear. The viruses are carried by large fractions of the human population and can integrate into the human genome, leading to a wide range of clinical manifestations of varied severity. Here, we present the first nine full and two partial ancient genomes of HHV-6A and 6B, dating as far back as the Italian Iron Age (ca. 1100-600 BCE). We demonstrate that large fractions of the current HHV-6 diversity were already well established in the human population by the 14th century CE. Our data suggests that HHV-6B integrated into the human genome at the latest before the 1st-6th century CE, with two integrated clades being populated by ancient DNA genomes in our phylogeny, which further supports that they originated from likely much older ancient founder events. Additionally, we show that all known inherited chromosomally integrated (ici-)HHV-6A clades were already represented in European historical populations, confirming that ici-HHV-6A no longer integrates into the human germline within populations of European ancestry and likely endogenized in early human history. Finally, our results demonstrate the unique suitability of archaeological remains and ancient DNA for the study of the evolution of integrated viruses in human populations.

evolutionary biology↗

bioRxiv2024

North Pontic crossroads: Mobility in Ukraine from the Bronze Age to the early modern period

The North Pontic region, which encompasses present-day Ukraine, was a crossroads of migration as it connected the vast Eurasian Steppe with Central Europe. We generated shotgun-sequenced genomic data for 91 individuals dating from around 7,000 BCE to 1,800 CE to study migration and mobility history in the region, with a particular focus on historically attested migrating groups during the Iron Age and the medieval period, such as Scythian, Chernyakhiv, Saltiv and Nogai associated peoples. We infer a high degree of temporal heterogeneity in ancestry, with fluctuating genetic affinities to present-day Western European, Eastern European, Western Steppe and East Asian groups. We also infer high heterogeneity in ancestry within geographically, culturally and socially defined groups. Despite this, we find that ancestry components which are widespread in Eastern and Central Europe have been present in the Ukraine region since the Bronze Age.

genomics↗

bioRxiv2023

A Refined Phylochronology of the Second Plague Pandemic in Western Eurasia

Although dozens of ancient Yersinia pestis genomes and a vast corpus of documentary data are available, the origin and spread of consecutive outbreaks of the Second Plague Pandemic in Europe (14th-18th c.) are still poorly understood. For the majority of ancient genomes, only radiocarbon dates spanning several decades are available, hampering an association with historically recorded plague outbreaks. Here, we present new genomic evidence of the Second Pandemic from 11 sites in England, Estonia, the Netherlands, Russia, and Switzerland yielding 11 Y. pestis genomes with >4-fold mean coverage dating to between 1349 and 1710. In addition, we present a novel approach for integrating the chronological information retrieved from phylogenetic analysis with their respective radiocarbon dates, based on a novel methodology offering more precise dating intervals. Together with a fine-grained analysis of documentarily recorded plague outbreaks, this allows us to tentatively associate all available Y. pestis genomes of the Second Pandemic with historically documented plague outbreaks. Through these combined multidisciplinary analytical efforts, our newly sequenced genomes can be attributed to the Black Death in Cambridge (England), the pestis tertia or pestis quarta in the late 14th century (Estonia), previously unknown branches emerging in the 15th century (Estonia, the Netherlands and England), and a widespread pandemic in Eastern Europe around 1500 (western Russia), which all seem to have originated from one or multiple reservoirs located in Central Europe. While the latter continued to harbour a major Y. pestis lineage at least until the 1630s, represented by new genomes of the Thirty Years War plague (Switzerland), another lineage consecutively spread into Europe between the 17th and 18th century from the Ottoman Empire, as evidenced by a genome associated with the Great Northern War plague (Estonia). By combining phylogenetic analysis with a systematic historical reconstruction based on textual sources and an innovative phylogenetically informed radiocarbon modelling (PhIRM), we offer a new groundbreaking interdisciplinary approach that solves several fundamental methodological challenges associated with phylogenetic and spatio-temporal reconstruction of historical pandemics.

genomics↗

bioRxiv2022

Ancient herpes simplex 1 genomes reveal recent viral structure in Eurasia

Human herpes simplex virus 1 (HSV-1), a life-long infection spread by oral contact, today infects a majority of adults globally1, yet no ancient HSV-1 genomes have yet been published. Phylogeographic clustering of sampled diversity into European, pan-Eurasian, and African groups2, 3 has suggested that the virus co-diverged with anatomically modern humans migrating out of Africa4, although a much younger origin has also been proposed5. The lack of ancient HSV-1 genomes, high rates of recombination, and high mobility of humans in the modern era have impeded the understanding of HSV-1s evolutionary history. Here we present three full ancient European HSV-1 genomes and one partial genome, dating to between the 3rd and 17th century CE, sequenced to up to 9.5x with paired human genomes up to 10.16x. These HSV-1 strains fall within modern Eurasian diversity. We estimate a mean mutation rate of 7.6 x 10-7 - 1.13 x 10-6 for non-African diversity leading to an estimated age of sampled modern Eurasian diversity to 4.68 (3.87 - 5.65) kya. Extrapolation of these rates indicate the age of sampled HSV-1 to 5.29 (4.60-6.12 kya, suggesting lineage replacement coinciding with late Neolithisation and implicating Bronze Age migrations6 in the distribution of HSV-1 through Eurasia.

genomics↗

bioRxiv2021

Ancestral contributions to contemporary European complex traits

The contemporary European genetic makeup formed in the last 8000 years as the combination of three main genetic components: the local Western Hunter-Gatherers, the incoming Neolithic Farmers from Anatolia and the Bronze Age component from the Pontic Steppes. When meeting into the post-Neolithic European environment, the genetic variants accumulated during their three distinct evolutionary histories mixed and came into contact with new environmental challenges. Here we investigate how this genetic legacy reflects on the complex trait landscape of contemporary European populations, using the Estonian Biobank as a case study. For the first time we directly connect the phenotypic information available from biobank samples with the genetic similarity to these ancestral groups, both at a genome-wide level and focusing on genomic regions associated with each of the 27 complex traits we investigated. We also found SNPs connected to pigmentation, cholesterol, sleep, diastolic blood pressure, and body mass index (BMI) to show signals of selection following the post Neolithic admixture events. We recapitulate existing knowledge about pigmentation traits, corroborate the connection between Steppe ancestry and height and highlight novel associations. Among others, we report the contribution of Hunter Gatherer ancestry towards high BMI and low blood cholesterol levels. Our results show that the ancient components that form the contemporary European genome were differentiated enough to contribute ancestry-specific signatures to the phenotypic variability displayed by contemporary individuals in at least 11 out of 27 of the complex traits investigated here.

genomics↗

bioRxiv2020

Genetic architecture of gene regulation in Indonesian populations identifies QTLs associated with local ancestry and archaic introgression

Lack of diversity in human genomics limits our understanding of the genetic underpinnings of complex traits, hinders precision medicine, and contributes to health disparities. To map genetic effects on gene regulation in the underrepresented Indonesian population, we have integrated genotype, gene expression, and CpG methylation data from 115 participants across three island populations that capture the major sources of genomic diversity on the region. In a comparison with a European dataset, we identify 166 uniquely Indonesia-specific eQTLs, highlighting the benefits of performing association studies on non-European populations. By combining local ancestry and archaic introgression inference eQTLs and methylQTLs, we identify regulatory loci driven by modern Papuan ancestry as well as introgressed Denisovan and Neanderthal variation. GWAS colocalization connects QTLs detected here to hematological traits. Our findings illustrate how local ancestry and archaic introgression drive variation in gene regulation across genetically distinct and in admixed populations.

genomics↗

bioRxiv2020

Genetic ancestry changes in Stone to Bronze Age transition in the East European plain

Transition from the Stone to the Bronze Age in Central and Western Europe was a period of major population movements originating from the Ponto-Caspian Steppe. Here, we report new genome-wide sequence data from 28 individuals from the territory north of this source area - from the under-studied Western part of present-day Russia, including Stone Age hunter-gatherers (10,800-4,250 cal BC) and Bronze Age farmers from the Corded Ware complex called Fatyanovo Culture (2,900-2,050 cal BC). We show that Eastern hunter-gatherer ancestry was present in Northwestern Russia already from around 10,000 BC. Furthermore, we see a clear change in ancestry with the arrival of farming - the Fatyanovo Culture individuals were genetically similar to other Corded Ware cultures, carrying a mixture of Steppe and European early farmer ancestry and thus likely originating from a fast migration towards the northeast from somewhere in the vicinity of modern-day Ukraine, which is the closest area where these ancestries coexisted from around 3,000 BC.

evolutionary biology↗

bioRxiv2020

AN ADMIXTURE SIGNAL IN ARMENIANS AROUND THE END OF THE BRONZE AGE REVEALS WIDESPREAD POPULATION MOVEMENT ACROSS THE MIDDLE EAST

The Armenians, a population inhabiting the region in West Asia known as the Armenian Highland, has been argued to show a remarkable degree of population continuity since the Early Neolithic. Here we test the degree of continuity of this population as well as its plausible origin, by collating modern and ancient genomic data, and adding a number of novel contemporary genomes. We show that Armenians have indeed remained unadmixed through the Neolithic and at least until the first part of the Bronze Age, and fail to find any support for historical suggestions by Herodotus of an input from the Balkans. However, we do detect a genetic input of Sardinian-like ancestry during or just after the Middle-Late Bronze Age. A similar input at approximately the same time was detected in East Africa, suggesting large-scale movement both North and South of the Middle East. Whether such large-scale population movement was a result of climatic or cultural changes is unclear, as well as the true source of gene flow remains an open question that needs to be addressed in future ancient DNA studies.

genomics↗

bioRxiv2017

Extensive farming in Estonia started through a sex-biased migration from the Steppe

Farming-based economies appear relatively late in Northeast Europe and the extent to which they involve genetic ancestry change is still poorly understood. Here we present the analyses of low coverage whole genome sequence data from five hunter-gatherers and five farmers of Estonia dated to 4,500 to 6,300 years before present. We find evidence of significant differences between the two groups in the composition of autosomal as well as mtDNA, X and Y chromosome ancestries. We find that Estonian hunter-gatherers of Comb Ceramic Culture are closest to Eastern hunter-gatherers. The Estonian first farmers of Corded Ware Culture show high similarity in their autosomes with Steppe Belt Late Neolithic/Bronze Age individuals, Caucasus hunter-gatherers and Iranian farmers while their X chromosomes are most closely related with the European Early Farmers of Anatolian descent. These findings suggest that the shift to intensive cultivation and animal husbandry in Estonia was triggered by the arrival of new people with predominantly Steppe ancestry, but whose ancestors had undergone sex-specific admixture with early farmers with Anatolian ancestry.

evolutionary biology↗