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Background: Hansen's disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease's complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period., Results: Here, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae's genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria., Conclusions: Our findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease's global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy's global history and can contribute to current models of M. leprae's worldwide dissemination, including interspecies transmissions., (© 2021. The Author(s).)

Tiwanaku civilization flourished in the Lake Titicaca basin between 500 and 1000 CE and at its apogee influenced wide areas across the southern Andes. Despite a considerable amount of archaeological data, little is known about the Tiwanaku population. We analyzed 17 low-coverage genomes from individuals dated between 300 and 1500 CE and demonstrated genetic continuity in the Lake Titicaca basin throughout this period, which indicates that the substantial cultural and political changes in the region were not accompanied by large-scale population movements. Conversely, the ritual center of Tiwanaku revealed high diversity, including individuals with primarily local genetic ancestry and those with foreign admixture or provenance from as far as the Amazon. Nonetheless, most human offerings associated with the Akapana platform exhibited pure Titicaca basin ancestry and dated to ca. 950 CE—the onset of Tiwanaku’s decline as a sociopolitical center. Our results strengthen the view of Tiwanaku as a complex and far-reaching polity.

Dogs are known to be the oldest animals domesticated by humans. Although many studies have examined wolf domestication, the geographic and temporal origin of this process is still being debated. To address this issue, our study sheds new light on the early stages of wolf domestication during the Magdalenian period (16-14 ka cal BP) in the Hegau Jura region (Southwestern Germany and Switzerland). By combining morphology, genetics, and isotopes, our multidisciplinary approach helps to evaluate alternate processes driving the early phases of domestication. The isotope analysis uncovered a restricted, low δ 15 N protein diet for all analyzed Gnirshöhle specimens, while morphological examinations and phylogenetic relationships did not unequivocally assign them to one or the other canid lineage. Intriguingly, the newly generated mitochondrial canid genomes span the entire genetic diversity of modern dogs and wolves. Such high mitochondrial diversity could imply that Magdalenian people tamed and reared animals originating from different wolf lineages. We discuss our results in light of three ecological hypotheses and conclude that both domestication and the existence of a specialized wolf ecomorph are highly probable. However, due to their proximity to humans and a restricted diet, we propose domestication as the most likely scenario explaining the patterns observed herein.

Yersinia pestis , the causative agent of plague, has been prevalent among humans for at least 5000 years, being accountable for several devastating epidemics in history, including the Black Death. Analyses of the genetic diversity of ancient strains of Y. pestis have shed light on the mechanisms of evolution and the spread of plague in Europe. However, many questions regarding the origins of the pathogen and its long persistence in Europe are still unresolved, especially during the late medieval time period. To address this, we present four newly assembled Y. pestis genomes from Eastern Europe (Poland and Southern Russia), dating from the fifteenth to eighteenth century AD. The analysis of polymorphisms in these genomes and their phylogenetic relationships with other ancient and modern Y. pestis strains may suggest several independent introductions of plague into Eastern Europe or its persistence in different reservoirs. Furthermore, with the reconstruction of a partial Y. pestis genome from rat skeletal remains found in a Polish ossuary, we were able to identify a potential animal reservoir in late medieval Europe. Overall, our results add new information concerning Y. pestis transmission and its evolutionary history in Eastern Europe. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

The maritime expansion of Scandinavian populations during the Viking Age (about AD 750-1050) was a far-flung transformation in world history 1,2 . Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci-including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response-in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.

Background: Recent advances in sequencing have facilitated large-scale analyses of the metagenomic composition of different samples, including the environmental microbiome of air, water, and soil, as well as the microbiome of living humans and other animals. Analyses of the microbiome of ancient human samples may provide insights into human health and disease, as well as pathogen evolution, but the field is still in its very early stages and considered highly challenging., Results: The metagenomic and pathogen content of Egyptian mummified individuals from different time periods was investigated via genetic analysis of the microbial composition of various tissues. The analysis of the dental calculus' microbiome identified Red Complex bacteria, which are correlated with periodontal diseases. From bone and soft tissue, genomes of two ancient pathogens, a 2200-year-old Mycobacterium leprae strain and a 2000-year-old human hepatitis B virus, were successfully reconstructed., Conclusions: The results show the reliability of metagenomic studies on Egyptian mummified individuals and the potential to use them as a source for the extraction of ancient pathogen DNA.

The cave bear (Ursus spelaeus) is one of the Late Pleistocene megafauna species that faced extinction at the end of the last ice age. Although it is represented by one of the largest fossil records in Europe and has been subject to several interdisciplinary studies including palaeogenetic research, its fate remains highly controversial. Here, we used a combination of hybridisation capture and next generation sequencing to reconstruct 59 new complete cave bear mitochondrial genomes (mtDNA) from 14 sites in Western, Central and Eastern Europe. In a Bayesian phylogenetic analysis, we compared them to 64 published cave bear mtDNA sequences to reconstruct the population dynamics and phylogeography during the Late Pleistocene. We found five major mitochondrial DNA lineages resulting in a noticeably more complex biogeography of the European lineages during the last 50,000 years than previously assumed. Furthermore, our calculated effective female population sizes suggest a drastic cave bear population decline starting around 40,000 years ago at the onset of the Aurignacian, coinciding with the spread of anatomically modern humans in Europe. Thus, our study supports a potential significant human role in the general extinction and local extirpation of the European cave bear and illuminates the fate of this megafauna species.

Human parvovirus B19 (B19V) is a ubiquitous human pathogen associated with a number of conditions, such as fifth disease in children and arthritis and arthralgias in adults. B19V is thought to evolve exceptionally rapidly among DNA viruses, with substitution rates previously estimated to be closer to those typical of RNA viruses. On the basis of genetic sequences up to ∼70 years of age, the most recent common ancestor of all B19V has been dated to the early 1800s, and it has been suggested that genotype 1, the most common B19V genotype, only started circulating in the 1960s. Here we present 10 genomes (63.9-99.7% genome coverage) of B19V from dental and skeletal remains of individuals who lived in Eurasia and Greenland from ∼0.5 to ∼6.9 thousand years ago (kya). In a phylogenetic analysis, five of the ancient B19V sequences fall within or basal to the modern genotype 1, and five fall basal to genotype 2, showing a long-term association of B19V with humans. The most recent common ancestor of all B19V is placed ∼12.6 kya, and we find a substitution rate that is an order of magnitude lower than inferred previously. Further, we are able to date the recombination event between genotypes 1 and 3 that formed genotype 2 to ∼5.0-6.8 kya. This study emphasizes the importance of ancient viral sequences for our understanding of virus evolution and phylogenetics., Competing Interests: The authors declare no conflict of interest.

Egypt, located on the isthmus of Africa, is an ideal region to study historical population dynamics due to its geographic location and documented interactions with ancient civilizations in Africa, Asia and Europe. Particularly, in the first millennium BCE Egypt endured foreign domination leading to growing numbers of foreigners living within its borders possibly contributing genetically to the local population. Here we present 90 mitochondrial genomes as well as genome-wide data sets from three individuals obtained from Egyptian mummies. The samples recovered from Middle Egypt span around 1,300 years of ancient Egyptian history from the New Kingdom to the Roman Period. Our analyses reveal that ancient Egyptians shared more ancestry with Near Easterners than present-day Egyptians, who received additional sub-Saharan admixture in more recent times. This analysis establishes ancient Egyptian mummies as a genetic source to study ancient human history and offers the perspective of deciphering Egypt's past at a genome-wide level.

We are writing in response to a recent critique by Emerson & Hickerson (2015), who challenge the evidence of a time-dependent bias in molecular rate estimates. This bias takes the form of a negative relationship between inferred evolutionary rates and the ages of the calibrations on which these estimates are based. Here, we present a summary of the evidence obtained from a broad range of taxa that supports a time-dependent bias in rate estimates, with a consideration of the potential causes of these observed trends. We also describe recent progress in improving the reliability of evolutionary rate estimation and respond to the concerns raised by Emerson & Hickerson (2015) about the validity of rates estimated from time-structured sequence data. In doing so, we hope to dispel some misconceptions and to highlight several research directions that will improve our understanding of time-dependent biases in rate estimates., (© 2015 John Wiley & Sons Ltd.)

Mitochondrial genomes represent a valuable source of data for evolutionary research, but studies of their short-term evolution have typically been limited to invertebrates, humans and laboratory organisms. Here we present a detailed study of 12 mitochondrial genomes that span a total of 385 transmissions in a well-documented 50-generation pedigree in which two lineages of chickens were selected for low and high juvenile body weight. These data allowed us to test the hypothesis of time-dependent evolutionary rates and the assumption of strict maternal mitochondrial transmission, and to investigate the role of mitochondrial mutations in determining phenotype. The identification of a non-synonymous mutation in ND4L and a synonymous mutation in CYTB, both novel mutations in Gallus, allowed us to estimate a molecular rate of 3.13 × 10(-7) mutations/site/year (95% confidence interval 3.75 × 10(-8)-1.12 × 10(-6)). This is substantially higher than avian rate estimates based upon fossil calibrations. Ascertaining which of the two novel mutations was present in an additional 49 individuals also revealed an instance of paternal inheritance of mtDNA. Lastly, an association analysis demonstrated that neither of the point mutations was strongly associated with the phenotypic differences between the two selection lines. Together, these observations reveal the highly dynamic nature of mitochondrial evolution over short time periods., (© 2015 The Authors.)

Evolutionary timescales can be estimated from genetic data using the molecular clock, often calibrated by fossil or geological evidence. However, estimates of molecular rates in mitochondrial DNA appear to scale negatively with the age of the clock calibration. Although such a pattern has been observed in a limited range of data sets, it has not been studied on a large scale in metazoans. In addition, there is uncertainty over the temporal extent of the time-dependent pattern in rate estimates. Here we present a meta-analysis of 239 rate estimates from metazoans, representing a range of timescales and taxonomic groups. We found evidence of time-dependent rates in both coding and non-coding mitochondrial markers, in every group of animals that we studied. The negative relationship between the estimated rate and time persisted across a much wider range of calibration times than previously suggested. This indicates that, over long time frames, purifying selection gives way to mutational saturation as the main driver of time-dependent biases in rate estimates. The results of our study stress the importance of accounting for time-dependent biases in estimating mitochondrial rates regardless of the timescale over which they are inferred.

Studies of DNA from ancient samples provide a valuable opportunity to gain insight into past evolutionary and demographic processes. Bayesian phylogenetic methods can estimate evolutionary rates and timescales from ancient DNA sequences, with the ages of the samples acting as calibrations for the molecular clock. Sample ages are often estimated using radiocarbon dating, but the associated measurement error is rarely taken into account. In addition, the total uncertainty quantified by converting radiocarbon dates to calendar dates is typically ignored. Here, we present a tool for incorporating both of these sources of uncertainty into Bayesian phylogenetic analyses of ancient DNA. This empirical calibrated radiocarbon sampler (ECRS) integrates the age uncertainty for each ancient sequence over the calibrated probability density function estimated for its radiocarbon date and associated error. We use the ECRS to analyse three ancient DNA data sets. Accounting for radiocarbon-dating and calibration error appeared to have little impact on estimates of evolutionary rates and related parameters for these data sets. However, analyses of other data sets, particularly those with few or only very old radiocarbon dates, might be more sensitive to using artificially precise sample ages and should benefit from use of the ECRS., (© 2014 John Wiley & Sons Ltd.)

The common practice of resettlement and the development of administrative and ceremonial systems shaped the population landscape of the Andean region under the Inca rule. The area surrounding Coropuna and Solimana volcanoes, in the Arequipa region (Peru), carried a high-density, multiethnic population. We studied the genetic variation among three pre-Columbian populations from three functionally diverse archaeological sites excavated in this region. By analyzing the genetic composition of a large ceremonial center (Acchaymarca), an isolated pastoral settlement (Tompullo 2), and an agricultural settlement characterized by architectural features rare in the region (Puca), we investigated the patterns of population movements and the distribution of genetic diversity. We obtained mitochondrial DNA sequences for 25 individuals and autosomal microsatellite profiles for 20 individuals from Acchaymarca and Puca sites. These were compared with previously published genetic data for Tompullo 2 and other pre-Columbian populations. We found differences among the genetic portraits of the three populations, congruent with the archaeologically described functions and characteristics of the sites. The Acchaymarca population had the highest genetic diversity and possessed the lowest number of unique mtDNA haplotypes. The Tompullo 2 population exhibited the lowest level of genetic diversity. The Puca population was distinct from the other two populations owing to a high frequency of haplogroup A haplotypes, what potentially explains the non-local character of the burial architecture. Our analyses of microsatellite data suggest that gene flow between sites was mostly mediated by females, which is consistent with ethnohistorical knowledge of the social organization of the pre-Columbian communities., (© 2014 Wiley Periodicals, Inc.)

Summary: Relaxed molecular clocks allow the phylogenetic estimation of evolutionary timescales even when substitution rates vary among branches. In analyses of large multigene datasets, it is often appropriate to use multiple relaxed-clock models to accommodate differing patterns of rate variation among genes. We present ClockstaR, a method for selecting the number of relaxed clocks for multigene datasets., Availability: ClockstaR is freely available for download at http://sydney.edu.au/science/biology/meep/software/.

In recent years, ancient DNA has increasingly been used for estimating molecular timescales, particularly in studies of substitution rates and demographic histories. Molecular clocks can be calibrated using temporal information from ancient DNA sequences. This information comes from the ages of the ancient samples, which can be estimated by radiocarbon dating the source material or by dating the layers in which the material was deposited. Both methods involve sources of uncertainty. The performance of bayesian phylogenetic inference depends on the information content of the data set, which includes variation in the DNA sequences and the structure of the sample ages. Various sources of estimation error can reduce our ability to estimate rates and timescales accurately and precisely. We investigated the impact of sample-dating uncertainties on the estimation of evolutionary timescale parameters using the software BEAST. Our analyses involved 11 published data sets and focused on estimates of substitution rate and root age. We show that, provided that samples have been accurately dated and have a broad temporal span, it might be unnecessary to account for sample-dating uncertainty in Bayesian phylogenetic analyses of ancient DNA. We also investigated the sample size and temporal span of the ancient DNA sequences needed to estimate phylogenetic timescales reliably. Our results show that the range of sample ages plays a crucial role in determining the quality of the results but that accurate and precise phylogenetic estimates of timescales can be made even with only a few ancient sequences. These findings have important practical consequences for studies of molecular rates, timescales, and population dynamics.

The growth of ancient DNA research has offered exceptional opportunities and raised great expectations, but has also presented some considerable challenges. One of the ongoing issues is the impact of post-mortem damage in DNA molecules. Nucleotide alterations and DNA strand breakages lead to a significant decrease in the quantity of DNA molecules of useful length in a sample and to errors in the final DNA sequences obtained. We present a model of age-dependent DNA damage and quantify the influence of that damage on subsequent steps in the sequencing process, including the polymerase chain reaction and cloning. Calculations using our model show that deposition conditions, rather than the age of a sample, have the greatest influence on the level of DNA damage. In turn, this affects the probability of interpreting an erroneous (possessing damage-derived mutations) sequence as being authentic. We also evaluated the effect of post-mortem damage on real data sets using a Bayesian phylogenetic approach. According to our study, damage-derived sequence alterations appear to have little impact on the final DNA sequences. This indicates the effectiveness of current methods for sequence authentication and validation.