The rise of ancient genomics has revolutionised our understanding of human prehistory but this work depends on the availability of suitable samples. Here we present a complete ancient human genome ...and oral microbiome sequenced from a 5700 year-old piece of chewed birch pitch from Denmark. We sequence the human genome to an average depth of 2.3× and find that the individual who chewed the pitch was female and that she was genetically more closely related to western hunter-gatherers from mainland Europe than hunter-gatherers from central Scandinavia. We also find that she likely had dark skin, dark brown hair and blue eyes. In addition, we identify DNA fragments from several bacterial and viral taxa, including Epstein-Barr virus, as well as animal and plant DNA, which may have derived from a recent meal. The results highlight the potential of chewed birch pitch as a source of ancient DNA.
Identifying the causes of similarities and differences in genetic disease prevalence among humans is central to understanding disease etiology. While present-day humans are not strongly ...differentiated, vast amounts of genomic data now make it possible to study subtle patterns of genetic variation. This allows us to trace our genomic history thousands of years into the past and its implications for the distribution of disease-associated variants today. Genomic analyses have shown that demographic processes shaped the distribution and frequency of disease-associated variants over time. Furthermore, local adaptation to new environmental conditions—including pathogens—has generated strong patterns of differentiation at particular loci. Researchers are also beginning to uncover the genetic architecture of complex diseases, affected by many variants of small effect. The field of population genomics thus holds great potential for providing further insights into the evolution of human disease.
Analysis of rapidly accumulating human genetic data from across the globe informs not only our understanding of population demographics but also historical adaptation to varying environments and susceptibility to disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Most ancient specimens contain very low levels of endogenous DNA, precluding the shotgun sequencing of many interesting samples because of cost. Ancient DNA (aDNA) libraries often contain <1% ...endogenous DNA, with the majority of sequencing capacity taken up by environmental DNA. Here we present a capture-based method for enriching the endogenous component of aDNA sequencing libraries. By using biotinylated RNA baits transcribed from genomic DNA libraries, we are able to capture DNA fragments from across the human genome. We demonstrate this method on libraries created from four Iron Age and Bronze Age human teeth from Bulgaria, as well as bone samples from seven Peruvian mummies and a Bronze Age hair sample from Denmark. Prior to capture, shotgun sequencing of these libraries yielded an average of 1.2% of reads mapping to the human genome (including duplicates). After capture, this fraction increased substantially, with up to 59% of reads mapped to human and enrichment ranging from 6- to 159-fold. Furthermore, we maintained coverage of the majority of regions sequenced in the precapture library. Intersection with the 1000 Genomes Project reference panel yielded an average of 50,723 SNPs (range 3,062–147,243) for the postcapture libraries sequenced with 1 million reads, compared with 13,280 SNPs (range 217–73,266) for the precapture libraries, increasing resolution in population genetic analyses. Our whole-genome capture approach makes it less costly to sequence aDNA from specimens containing very low levels of endogenous DNA, enabling the analysis of larger numbers of samples.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present results of the largest multidisciplinary human mobility investigation to date of skeletal remains from present-day Denmark encompassing the 3rd and 2nd millennia BC. Through a ...multi-analytical approach based on 88 individuals from 37 different archaeological localities in which we combine strontium isotope and radiocarbon analyses together with anthropological investigations, we explore whether there are significant changes in human mobility patterns during this period. Overall, our data suggest that mobility of people seems to have been continuous throughout the 3rd and 2nd millennia BC. However, our data also indicate a clear shift in mobility patterns from around 1600 BC onwards, with a larger variation in the geographical origin of the migrants, and potentially including more distant regions. This shift occurred during a transition period at the beginning of the Nordic Bronze Age at a time when society flourished, expanded and experienced an unprecedented economic growth, suggesting that these aspects were closely related.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Over the past three decades, studies of ancient biomolecules-particularly ancient DNA, proteins, and lipids-have revolutionized our understanding of evolutionary history. Though initially fraught ...with many challenges, today the field stands on firm foundations. Researchers now successfully retrieve nucleotide and amino acid sequences, as well as lipid signatures, from progressively older samples, originating from geographic areas and depositional environments that, until recently, were regarded as hostile to long-term preservation of biomolecules. Sampling frequencies and the spatial and temporal scope of studies have also increased markedly, and with them the size and quality of the data sets generated. This progress has been made possible by continuous technical innovations in analytical methods, enhanced criteria for the selection of ancient samples, integrated experimental methods, and advanced computational approaches. Here, we discuss the history and current state of ancient biomolecule research, its applications to evolutionary inference, and future directions for this young and exciting field.
The lethally maltreated body of Vittrup Man was deposited in a Danish bog, probably as part of a ritualised sacrifice. It happened between c. 3300 and 3100 cal years BC, i.e., during the period of ...the local farming-based Funnel Beaker Culture. In terms of skull morphological features, he differs from the majority of the contemporaneous farmers found in Denmark, and associates with hunter-gatherers, who inhabited Scandinavia during the previous millennia. His skeletal remains were selected for transdisciplinary analysis to reveal his life-history in terms of a population historical perspective. We report the combined results of an integrated set of genetic, isotopic, physical anthropological and archaeological analytical approaches. Strontium signature suggests a foreign birthplace that could be in Norway or Sweden. In addition, enamel oxygen isotope values indicate that as a child he lived in a colder climate, i.e., to the north of the regions inhabited by farmers. Genomic data in fact demonstrates that he is closely related to Mesolithic humans known from Norway and Sweden. Moreover, dietary stable isotope analyses on enamel and bone collagen demonstrate a fisher-hunter way of life in his childhood and a diet typical of farmers later on. Such a variable life-history is also reflected by proteomic analysis of hardened organic deposits on his teeth, indicating the consumption of forager food (seal, whale and marine fish) as well as farmer food (sheep/goat). From a dietary isotopic transect of one of his teeth it is shown that his transfer between societies of foragers and farmers took place near to the end of his teenage years.
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17.
Imputation of ancient human genomes Sousa da Mota, Bárbara; Rubinacci, Simone; Cruz Dávalos, Diana Ivette ...
Nature communications,
06/2023, Volume:
14, Issue:
1
Journal Article
Peer reviewed
Open access
Due to postmortem DNA degradation and microbial colonization, most ancient genomes have low depth of coverage, hindering genotype calling. Genotype imputation can improve genotyping accuracy for ...low-coverage genomes. However, it is unknown how accurate ancient DNA imputation is and whether imputation introduces bias to downstream analyses. Here we re-sequence an ancient trio (mother, father, son) and downsample and impute a total of 43 ancient genomes, including 42 high-coverage (above 10x) genomes. We assess imputation accuracy across ancestries, time, depth of coverage, and sequencing technology. We find that ancient and modern DNA imputation accuracies are comparable. When downsampled at 1x, 36 of the 42 genomes are imputed with low error rates (below 5%) while African genomes have higher error rates. We validate imputation and phasing results using the ancient trio data and an orthogonal approach based on Mendel's rules of inheritance. We further compare the downstream analysis results between imputed and high-coverage genomes, notably principal component analysis, genetic clustering, and runs of homozygosity, observing similar results starting from 0.5x coverage, except for the African genomes. These results suggest that, for most populations and depths of coverage as low as 0.5x, imputation is a reliable method that can improve ancient DNA studies.
The Pleistocene presence of the genus Homo in continental Southeast Asia is primarily evidenced by a sparse stone tool record and rare human remains. Here we report a Middle Pleistocene hominin ...specimen from Laos, with the discovery of a molar from the Tam Ngu Hao 2 (Cobra Cave) limestone cave in the Annamite Mountains. The age of the fossil-bearing breccia ranges between 164-131 kyr, based on the Bayesian modelling of luminescence dating of the sedimentary matrix from which it was recovered, U-series dating of an overlying flowstone, and U-series-ESR dating of associated faunal teeth. Analyses of the internal structure of the molar in tandem with palaeoproteomic analyses of the enamel indicate that the tooth derives from a young, likely female, Homo individual. The close morphological affinities with the Xiahe specimen from China indicate that they belong to the same taxon and that Tam Ngu Hao 2 most likely represents a Denisovan.
The Gjerrild burial provides the largest and best-preserved assemblage of human skeletal material presently known from the Single Grave Culture (SGC) in Denmark. For generations it has been debated ...among archaeologists if the appearance of this archaeological complex represents a continuation of the previous Neolithic communities, or was facilitated by incoming migrants. We sampled and analysed five skeletons from the Gjerrild cist, buried over a period of c. 300 years, 2600/2500-2200 cal BCE. Despite poor DNA preservation, we managed to sequence the genome (>1X) of one individual and the partial genomes (0.007X and 0.02X) of another two individuals. Our genetic data document a female (Gjerrild 1) and two males (Gjerrild 5 + 8), harbouring typical Neolithic K2a and HV0 mtDNA haplogroups, but also a rare basal variant of the R1b1 Y-chromosomal haplogroup. Genome-wide analyses demonstrate that these people had a significant Yamnaya-derived (i.e. steppe) ancestry component and a close genetic resemblance to the Corded Ware (and related) groups that were present in large parts of Northern and Central Europe at the time. Assuming that the Gjerrild skeletons are genetically representative of the population of the SGC in broader terms, the transition from the local Neolithic Funnel Beaker Culture (TRB) to SGC is not characterized by demographic continuity. Rather, the emergence of SGC in Denmark was part of the Late Neolithic and Early Bronze Age population expansion that swept across the European continent in the 3rd millennium BCE, resulting in various degrees of genetic replacement and admixture processes with previous Neolithic populations.
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Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation ...of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D) demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may contribute to the observed disparity in T2D incidence rates across ethnic populations.
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