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International audience; Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

Bartonet al.1raise several statistical concerns regarding our original analyses2that highlight the challenge of inferring natural selection using ancient genomic data. We show here that these concerns have limited impact on our original conclusions. Specifically, we recover the same signature of enrichment for high FSTvalues at the immune loci relative to putatively neutral sites after switching the allele frequency estimation method to a maximum likelihood approach, filtering to only consider known human variants, and down-sampling our data to the same mean coverage across sites. Furthermore, using permutations, we show that the rs2549794 variant nearERAP2continues to emerge as the strongest candidate for selection (p = 1.2×10−5), falling below the Bonferroni-corrected significance threshold recommended by Bartonet al. Importantly, the evidence for selection onERAP2is further supported by functional data demonstrating the impact of theERAP2genotype on the immune response toY. pestisand by epidemiological data from an independent group showing that the putatively selected allele during the Black Death protects against severe respiratory infection in contemporary populations.

The medieval period in Denmark saw increasing urbanization with the development of more heavily structured towns focused around market centers. This was influenced by de-population in the mid-fourteenth century leading to socioeconomic and political restructuring. It has been suggested that these changes would have influenced population health, with disparities between rural and urban contexts, although bioarchaeological studies have thus far revealed inconsistent patterns. Using a microscopic approach to examine enamel developmental defects alongside mortality profiles, this research examines population differences in health and stress for urban and rural sites in and around the town of Horsens. The sample encompasses a rural site that went out of use by the mid-fourteenth century (Tirup), another rural site that saw continued use into the sixteenth century (Sejet), and an urban site that was contemporary with Sejet (Ole Wormsgade). The findings suggest site differences in mortality and early life stress, with some temporal patterning. The population at Tirup experienced more stress and reduced survivorship in the younger segment of the population. Temporal changes at the other two sites suggest a decrease in survivorship in the period from AD 1250 to AD 1350, with an increase in survivorship in the subsequent period (AD 1350–1400). Individuals at Sejet also experienced stress earlier in childhood than those at Ole Wormsgade, but the mortality patterns are similar between the two sites. This speaks to the complex nature of urbanization in this period in Denmark and provides insight into how populations respond to stress while experiencing a slow rate of urbanization.

Dental enamel defects have been used extensively in past human populations to elucidate patterns of health and physiological disruption (often simply referred to as stress). These defects are most commonly assessed through visual examination and used to infer such information as the frequency and age at occurrence of stress events. However, a microscopic approach makes it possible to more consistently identify patterns of growth and growth disruption in greater detail than that possible with traditional macroscopic techniques. Such microscopic studies are being increasingly explored in bioarchaeology, but this area of investigation has not seen extensive application to zooarchaeological material. Consequently, enamel defects in general have not been integrated as heavily in this field. A species of particular importance within the modern context of climate change is the barren-ground caribou (Rangifer tarandus groenlandicus). This species has been a crucial species to the human populations throughout the Arctic for thousands of years, and herd fluctuations have in the past shaped the human experience. The study of past stress in these populations could provide significant historical insight into herd patterns, which would have impacted subsistence and mobility patterns, and traditional use of these animals among both past and contemporary human populations. This paper presents the results of a pilot study using the Olympus LEXT Laser-Scanning Confocal Microscope OLS4000 to evaluate enamel growth in an archaeological caribou tooth from the LdFa-1 site (a large caribou hunting site located in the deep interior of southern Baffin Island). Our study demonstrates the potential of this technology to capture enamel surface microstructures and to provide greater insight into the fine patterns of growth arrest within this zooarchaeological context.

Bioarchaeology as a field of study can contribute important insights to our understanding of how stress-related phenomena experienced in childhood influence later life conditions. One area that is especially effective is looking at the dental enamel surface microstructures reflecting patterns of growth and growth disruption. Since dental enamel grows incrementally, and because it does not remodel once formed, a record of growth disruption (formed during childhood) is preserved for the rest of an individuals' life. Enamel surface defects are commonly observed macroscopically as enamel hypoplasia. However, this method does not capture the smaller defects reflecting a disruption in only a few of the growth lines visible on the tooth surface. Previous approaches to the assessment of these structures have included scanning electron microscopes and polarized light microscopes with photomontaging and z-stacking capacity. This paper presents the application of the Olympus LEXT 3D Laser Measuring Microscope OLS4000 and Olympus LEXT analytical software to capture and examine dental enamel surface microstructures. The use of the LEXT for these purposes is critically assessed, and the strengths and challenges discussed. Recommendations are made for future application of this instrument to bioarchaeological research.

Objectives: In the 14th century AD, medieval Europe was severely affected by the Great European Famine as well as repeated bouts of disease, including the Black Death, causing major demographic shifts. This high volatility led to increased mobility and migration due to new labor and economic opportunities, as evidenced by documentary and stable isotope data. This study uses ancient DNA (aDNA) isolated from skeletal remains to examine whether evidence for large-scale population movement can be gleaned from the complete mitochondrial genomes of 264 medieval individuals from England (London) and Denmark. Materials and Methods: Using a novel library-conserving approach to targeted capture, we recovered 264 full mitochondrial genomes from the petrous portion of the temporal bones and teeth and compared genetic diversity across the medieval period within and between English (London) and Danish populations and with contemporary populations through population pairwise Φ ST analysis. Results: We find no evidence of significant differences in genetic diversity spatially or temporally in our dataset, yet there is a high degree of haplotype diversity in our medieval samples with little exact sequence sharing. Discussion: The mitochondrial genomes of both medieval Londoners and medieval Danes suggest high mitochondrial diversity before, during and after the Black Death. While our mitochondrial genomic data lack geographically correlated signals, these data could be the result of high, continual female migration before and after the Black Death or may simply indicate a large female effective population size unaffected by the upheaval of the medieval period. Either scenario suggests a genetic resiliency in areas of northwestern medieval Europe.

Developmental plasticity, or the ability of physiological development to change in response to environmental pressures (external and internal), results in permanent physiological changes that can shape the later life health experiences of an individual. The timing of non-specific stress in relation to growth and development is critical to this interaction. Dental enamel provides detailed information on the timing of non-specific stress experiences, which may be considered in relation to growth in other physiological systems developing at the same time to elucidate the impact of one on the other. Examples of parallel developing systems include the immune, nervous, cardiovascular, respiratory, renal, and digestive systems (Chamley et al. 2005; MacGregor 2008; Bee & Boyd 2010). This research investigates these patterns through the consideration markers of enamel growth disruption known as accentuated striae of Retzius (AS) in relation to stature and body proportions in human skeletal remains. Anthropometrics and dental samples were collected from two medieval Danish cemetery samples. Residuals were calculated using linear regression from stature in the grave and all metrics were considered in relation to a total number of AS for each individual. A life course approach was also taken by considering AS at different stages of crown development in relation to each metric. Results indicate potential associations between AS and skeletal metrics (particularly tibial length and stature). These are most apparent in relation to AS rates in enamel developing from approximately 2 to 4.8 years of age. These results point to the utility of taking a life course approach in which enamel development is considered in relation to patterns of skeletal growth. Certain limitations and the need for further developments are highlighted by the nature of the results.

The influence of early life stress on later life experiences has become a major focus of research in medicine and more recently in bioarchaeology. Dental enamel, which preserves a record of childhood stress events, represents an important resource for this investigation when paired with the information from adult skeletal remains, such as age at death. The purpose of this research was to use a life history approach to the exploration of sex differences in the relationship between childhood stress and adult longevity by examining accentuated striae of Retzius (AS). A medieval Danish sample (n = 70) drawn from the rural cemetery of Sejet and the urban cemetery of Ole Wormsgade was considered for AS and age at death. The results suggest sex differences in survivorship, with more stress being associated with reduced survivorship in males and increased survivorship in females. A consideration of AS formation time also suggests a difference in the impact of developmental timing between males and females. These results are interpreted in terms of differential frailty and selective mortality, drawing in both biomedical and cultural perspectives.