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We present palaeogenomes of three morphologically unidentified Anatolian equids dating to the first millennium BCE, sequenced to a coverage of 0.6-6.4×. Mitochondrial DNA haplotypes of the Anatolian individuals clustered with those of Equus hydruntinus (or Equus hemionus hydruntinus), the extinct European wild ass, secular name 'hydruntine'. Further, the Anatolian wild ass whole genome profiles fell outside the genomic diversity of other extant and past Asiatic wild ass (E. hemionus) lineages. These observations suggest that the three Anatolian wild asses represent hydruntines, making them the latest recorded survivors of this lineage, about a millennium later than the latest observations in the zooarchaeological record. Our mitogenomic and genomic analyses indicate that E. h. hydruntinus was a clade belonging to ancient and present-day E. hemionus lineages that radiated possibly between 0.6 and 0.8 Mya. We also find evidence consistent with recent gene flow between hydruntines and Middle Eastern wild asses. Analyses of genome-wide heterozygosity and runs of homozygosity suggest that the Anatolian wild ass population may have lost genetic diversity by the mid-first millennium BCE, a possible sign of its eventual demise., (© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

To provide a historic snapshot as regards the evolution of headache treatment throughout the human history, i.e. starting from trepanation to perisutural botulinum toxin (BoNT) injections. Ancient surgeons had aimed to reach the cranium with trepanation (a surgical operation) for headache. As BoNT inhibits the release of nociceptive and pro-inflammatory neuropeptides, it has been recently suggested as an effective alternative in the prophylactic treatment of chronic migraine headache. Chronic migraine is a complex neurological disorder for which the underlying pathophysiology is yet not totally explained. According to the generally accepted hypotheses, peripheral neurogenic activation and central trigeminal sensitization are the two main mechanisms through which its pain develops. Since the headache most commonly occurs around the perisutural areas, and as the primary pathogenesis stem from the meningeal nerve fibers; collateral sensorial branches of the meningeal nerves can be optimal paths to transport BoNT inside the cranium. Concerning the therapeutic efficacy, we anticipate that perisutural injections would be technically challenging with blind techniques and actually possible only if performed under an imaging guidance, e.g. very conveniently with high frequency ultrasound.

Conditions in the early stages of life shape body size and proportions. This study includes individuals who came from different socio-economic conditions and worked in physically demanding jobs in childhood. By determining the body sizes of these individuals and evaluating the proportional relationships between several groups, the goal was to understand the effect levels of socio-economic levels and working conditions on the body. For this purpose, an anthropometric study was conducted on 623 males and females between the ages of 20 and 45 living in Samsun, Turkey. The study sample consisted of four different groups. It was divided into two main groups of high and low socio-economic level, and the low socio-economic group was divided into two subgroups of heavy-worker and nonheavy-worker. The results demonstrated that socio-economic differences in the size and proportions of the individuals were statistically significant (p<0.05). The high socio-economic group had the highest values in all measures. External factors affected the lower limbs more than the upper limbs. The measurement most affected by these factors was leg length. Longer legs characterized the high socio-economic group, while longer arms characterized both low socio-economic groups. The relative differences observed can be said to derive from the distal limbs. This finding was valid for both sexes. The average values were close to each other in the low socio-economic group, for which the aim was to comprehend the effects of heavy working conditions. However, differences in proportional relationships were more significant. In this context, it was seen that heavy labour also affected growth, in addition to the well-known factors encountered during the growth period, such as nutrition, health, and illness. The observed changes were more significant in males than in females. Thus, it can be said that males were more affected by physiological and physical conditions.

We present a spatiotemporal picture of human genetic diversity in Anatolia, Iran, Levant, South Caucasus, and the Aegean, a broad region that experienced the earliest Neolithic transition and the emergence of complex hierarchical societies. Combining 35 new ancient shotgun genomes with 382 ancient and 23 present-day published genomes, we found that genetic diversity within each region steadily increased through the Holocene. We further observed that the inferred sources of gene flow shifted in time. In the first half of the Holocene, Southwest Asian and the East Mediterranean populations homogenized among themselves. Starting with the Bronze Age, however, regional populations diverged from each other, most likely driven by gene flow from external sources, which we term "the expanding mobility model." Interestingly, this increase in inter-regional divergence can be captured by outgroup-f 3 -based genetic distances, but not by the commonly used F ST statistic, due to the sensitivity of F ST , but not outgroup-f 3 , to within-population diversity. Finally, we report a temporal trend of increasing male bias in admixture events through the Holocene., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Upper Mesopotamia played a key role in the Neolithic Transition in Southwest Asia through marked innovations in symbolism, technology, and diet. We present 13 ancient genomes (c. 8500 to 7500 cal BCE) from Pre-Pottery Neolithic Çayönü in the Tigris basin together with bioarchaeological and material culture data. Our findings reveal that Çayönü was a genetically diverse population, carrying mixed ancestry from western and eastern Fertile Crescent, and that the community received immigrants. Our results further suggest that the community was organized along biological family lines. We document bodily interventions such as head shaping and cauterization among the individuals examined, reflecting Çayönü's cultural ingenuity. Last, we identify Upper Mesopotamia as the likely source of eastern gene flow into Neolithic Anatolia, in line with material culture evidence. We hypothesize that Upper Mesopotamia's cultural dynamism during the Neolithic Transition was the product not only of its fertile lands but also of its interregional demographic connections.

Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic., (© 2021. The Author(s).)

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic.

The history of human inbreeding is controversial. 1 In particular, how the development of sedentary and/or agricultural societies may have influenced overall inbreeding levels, relative to those of hunter-gatherer communities, is unclear. 2-5 Here, we present an approach for reliable estimation of runs of homozygosity (ROHs) in genomes with ≥3× mean sequence coverage across >1 million SNPs and apply this to 411 ancient Eurasian genomes from the last 15,000 years. 5-34 We show that the frequency of inbreeding, as measured by ROHs, has decreased over time. The strongest effect is associated with the Neolithic transition, but the trend has since continued, indicating a population size effect on inbreeding prevalence. We further show that most inbreeding in our historical sample can be attributed to small population size instead of consanguinity. Cases of high consanguinity were rare and only observed among members of farming societies in our sample. Despite the lack of evidence for common consanguinity in our ancient sample, consanguineous traditions are today prevalent in various modern-day Eurasian societies, 1 , 35-37 suggesting that such practices may have become widespread within the last few millennia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Uniparentally-inherited markers on mitochondrial DNA (mtDNA) and the non-recombining regions of the Y chromosome (NRY), have been used for the past 30 years to investigate the history of humans from a maternal and paternal perspective. Researchers have preferred mtDNA due to its abundance in the cells, and comparatively high substitution rate. Conversely, the NRY is less susceptible to back mutations and saturation, and is potentially more informative than mtDNA owing to its longer sequence length. However, due to comparatively poor NRY coverage via shotgun sequencing, and the relatively low and biased representation of Y-chromosome variants on capture assays such as the 1240 k, ancient DNA studies often fail to utilize the unique perspective that the NRY can yield. Here we introduce a new DNA enrichment assay, coined YMCA (Y-mappable capture assay), that targets the "mappable" regions of the NRY. We show that compared to low-coverage shotgun sequencing and 1240 k capture, YMCA significantly improves the mean coverage and number of sites covered on the NRY, increasing the number of Y-haplogroup informative SNPs, and allowing for the identification of previously undiscovered variants. To illustrate the power of YMCA, we show that the analysis of ancient Y-chromosome lineages can help to resolve Y-chromosomal haplogroups. As a case study, we focus on H2, a haplogroup associated with a critical event in European human history: the Neolithic transition. By disentangling the evolutionary history of this haplogroup, we further elucidate the two separate paths by which early farmers expanded from Anatolia and the Near East to western Europe., (© 2021. The Author(s).)

The social organization of the first fully sedentary societies that emerged during the Neolithic period in Southwest Asia remains enigmatic, 1 mainly because material culture studies provide limited insight into this issue. However, because Neolithic Anatolian communities often buried their dead beneath domestic buildings, 2 household composition and social structure can be studied through these human remains. Here, we describe genetic relatedness among co-burials associated with domestic buildings in Neolithic Anatolia using 59 ancient genomes, including 22 new genomes from Aşıklı Höyük and Çatalhöyük. We infer pedigree relationships by simultaneously analyzing multiple types of information, including autosomal and X chromosome kinship coefficients, maternal markers, and radiocarbon dating. In two early Neolithic villages dating to the 9th and 8th millennia BCE, Aşıklı Höyük and Boncuklu, we discover that siblings and parent-offspring pairings were frequent within domestic structures, which provides the first direct indication of close genetic relationships among co-burials. In contrast, in the 7th millennium BCE sites of Çatalhöyük and Barcın, where we study subadults interred within and around houses, we find close genetic relatives to be rare. Hence, genetic relatedness may not have played a major role in the choice of burial location at these latter two sites, at least for subadults. This supports the hypothesis that in Çatalhöyük, 3-5 and possibly in some other Neolithic communities, domestic structures may have served as burial location for social units incorporating biologically unrelated individuals. Our results underscore the diversity of kin structures in Neolithic communities during this important phase of sociocultural development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Examining diagenetic parameters such as the organic carbonate contents and the crystallinity of bone apatite quantify the post-mortem alteration of bone. Burial conditions are one of the factors that can influence the diagenesis process. We studied the changes to the organic and mineral components and crystallinity of human bone remains from five Medieval sites in Turkey: Hakemi Use, Komana, İznik, Oluz Höyük and Tasmasor using Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and principal component analysis (PCA). Analysis of spectral band ratios related to organic and mineral components of bone demonstrated differences in the molecular content in the skeletal remains from the five sites. In order to examine the degree of carbonation of a phosphate matrix, curve-fitting procedures were applied to the carbonate band. We found that the infrared crystallinity index appears to not be sensitive to carbonate content at room temperature for the bone remains studied here. The recrystallization process in bone remains behaved differently among the archaeological sites. The results demonstrate that the burial environments differently affect the organic and mineral components of archaeological bone remains., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Here, we report genome-wide data analyses from 110 ancient Near Eastern individuals spanning the Late Neolithic to Late Bronze Age, a period characterized by intense interregional interactions for the Near East. We find that 6 th millennium BCE populations of North/Central Anatolia and the Southern Caucasus shared mixed ancestry on a genetic cline that formed during the Neolithic between Western Anatolia and regions in today's Southern Caucasus/Zagros. During the Late Chalcolithic and/or the Early Bronze Age, more than half of the Northern Levantine gene pool was replaced, while in the rest of Anatolia and the Southern Caucasus, we document genetic continuity with only transient gene flow. Additionally, we reveal a genetically distinct individual within the Late Bronze Age Northern Levant. Overall, our study uncovers multiple scales of population dynamics through time, from extensive admixture during the Neolithic period to long-distance mobility within the globalized societies of the Late Bronze Age. VIDEO ABSTRACT., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

It has been hypothesized that the Neolithic transition towards an agricultural and pastoralist economy facilitated the emergence of human-adapted pathogens. Here, we recovered eight Salmonella enterica subsp. enterica genomes from human skeletons of transitional foragers, pastoralists and agropastoralists in western Eurasia that were up to 6,500 yr old. Despite the high genetic diversity of S. enterica, all ancient bacterial genomes clustered in a single previously uncharacterized branch that contains S. enterica adapted to multiple mammalian species. All ancient bacterial genomes from prehistoric (agro-)pastoralists fall within a part of this branch that also includes the human-specific S. enterica Paratyphi C, illustrating the evolution of a human pathogen over a period of 5,000 yr. Bacterial genomic comparisons suggest that the earlier ancient strains were not host specific, differed in pathogenic potential and experienced convergent pseudogenization that accompanied their downstream host adaptation. These observations support the concept that the emergence of human-adapted S. enterica is linked to human cultural transformations.

Objective: The inhabitants of several sites in the Upper Tigris Valley, such as Hakemi Use, domesticated animals and cereals during the Pottery Neolithic period, while the inhabitants in this valley were hunter-gatherers in the Pre-Pottery Neolithic period, consuming freshwater and terrestrial food resources. However, there is considerable uncertainty surrounding whether or not changes in dietary food composition accompanied the shift in food production away from foraging. In order to reveal the impact of the development of agriculture on the human diet over the Pre-Pottery and Pottery Neolithic periods in this region, we analyzed the isotopic compositions of amino acids from the farmers at the Hakemi Use Pottery Neolithic site, and compared them with those from the Pre-Pottery hunter-gatherers in the close region., Materials and Methods: Herein, we report the nitrogen isotopic compositions of amino acids, as well as both carbon and nitrogen isotopic compositions of bulk collagen, from human and faunal remains collected from Hakemi Use., Results: Whereas freshwater resources were consumed by hunter-gatherers in this region during the Pre-Pottery period, the δ 15 N values of glutamic acid (δ 15 N Glu ) and phenylalanine (δ 15 N Phe ) suggest that freshwater food resources were rarely consumed by inhabitants following the development of agriculture., Discussion: Despite living in similar settings by the Tigris as its inhabitants during the Pre-Pottery period, the farmers of the Pottery Neolithic period depended less on freshwater resources for their diets relative to the hunter-gatherers of the Pre-Pottery Neolithic period., (© 2019 Wiley Periodicals, Inc.)

The archaeological documentation of the development of sedentary farming societies in Anatolia is not yet mirrored by a genetic understanding of the human populations involved, in contrast to the spread of farming in Europe [1-3]. Sedentary farming communities emerged in parts of the Fertile Crescent during the tenth millennium and early ninth millennium calibrated (cal) BC and had appeared in central Anatolia by 8300 cal BC [4]. Farming spread into west Anatolia by the early seventh millennium cal BC and quasi-synchronously into Europe, although the timing and process of this movement remain unclear. Using genome sequence data that we generated from nine central Anatolian Neolithic individuals, we studied the transition period from early Aceramic (Pre-Pottery) to the later Pottery Neolithic, when farming expanded west of the Fertile Crescent. We find that genetic diversity in the earliest farmers was conspicuously low, on a par with European foraging groups. With the advent of the Pottery Neolithic, genetic variation within societies reached levels later found in early European farmers. Our results confirm that the earliest Neolithic central Anatolians belonged to the same gene pool as the first Neolithic migrants spreading into Europe. Further, genetic affinities between later Anatolian farmers and fourth to third millennium BC Chalcolithic south Europeans suggest an additional wave of Anatolian migrants, after the initial Neolithic spread but before the Yamnaya-related migrations. We propose that the earliest farming societies demographically resembled foragers and that only after regional gene flow and rising heterogeneity did the farming population expansions into Europe occur., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Leprosy was rare in Europe during the Roman period, yet its prevalence increased dramatically in medieval times. We examined human remains, with paleopathological lesions indicative of leprosy, dated to the 6th-11th century AD, from Central and Eastern Europe and Byzantine Anatolia. Analysis of ancient DNA and bacterial cell wall lipid biomarkers revealed Mycobacterium leprae in skeletal remains from 6th-8th century Northern Italy, 7th-11th century Hungary, 8th-9th century Austria, the Slavic Greater Moravian Empire of the 9th-10th century and 8th-10th century Byzantine samples from Northern Anatolia. These data were analyzed alongside findings published by others. M. leprae is an obligate human pathogen that has undergone an evolutionary bottleneck followed by clonal expansion. Therefore M. leprae genotypes and sub-genotypes give information about the human populations they have infected and their migration. Although data are limited, genotyping demonstrates that historical M. leprae from Byzantine Anatolia, Eastern and Central Europe resembles modern strains in Asia Minor rather than the recently characterized historical strains from North West Europe. The westward migration of peoples from Central Asia in the first millennium may have introduced different M. leprae strains into medieval Europe and certainly would have facilitated the spread of any existing leprosy. The subsequent decline of M. leprae in Europe may be due to increased host resistance. However, molecular evidence of historical leprosy and tuberculosis co-infections suggests that death from tuberculosis in leprosy patients was also a factor., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The question of the presence of organized violence in the Neolithic settlements in Middle East has been debated. This paper presents possible examples of organized violence from the Neolithic period, representing early examples of settlements in Anatolia, to the Early Bronze Age, which provides the early instances of central authority. Most injuries detected among Neolithic populations in Anatolia have been associated with daily activities. Although individual examples of interpersonal violence exist among Neolithic and Chalcolithic populations in Anatolia, but they are far from representing organized violence. On the other hand the Early Bronze Age populations present clear evidence of perimortem wounds, mass burials, high frequency of cranial fractures, walls surrounding cities, and metal weapons in Anatolia. This suggests an increased evidence of organized violence in EBA Anatolia. Based on bioarchaeological data, it is concluded that violence in these settlements resulted from one or more ecological and social factors. However, each settlement might have peculiar reason for fighting., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The aim of this study was to assess the detection of proximal caries in primary teeth at three different tube potentials using Ektaspeed films, storage phosphor plates (SPPs), and a charge-coupled device (CCD). Fifty-three extracted human primary molars with natural proximal caries were radiographed with three different imaging modalities--Digora Optime SPP system, RVGui CCD system, and Ektaspeed films--at 50-, 65-, and 70-kV tube potentials. Three observers scored the resultant images for the presence or absence of caries. The definitive diagnosis was determined by stereomicroscopic assessment. The diagnostic accuracy for each imaging modality was expressed as the area under the receiver operating characteristic curves (A(z)). Differences among the A(z) values were assessed using two-way ANOVA and t tests. Kappa was used to measure inter- and intra-observer agreement. Higher accuracy was found for SPPs compared to film and CCD images at all tube potentials. Accuracy was significantly different only at 50-kV tube setting in favor of SPPs (p < 0.05). Inter- and intra-observer agreement was high for all systems. A SPP system can be recommended for dental peadodontic clinics particularly with 50-kV tube potential for the diagnosis of proximal caries since further advantages include the elimination of chemical processing, image enhancement, and a better low-contrast detectability performance.

Inter-population variation of cranial morphology, which plays an important role in human evolution studies and biological research, can be studied morphologically and metrically. Geometric morphometry compares body forms using specific landmarks determined by anatomical prominences. The aim of this study was to identify cranial shape differences between the crania of Byzantium period humans and modern humans. Variability in cranial shape was examined using the geometric morphometric technique based on landmark coordinates. Landmark coordinate data were collected from two-dimensional digital photogrammetry and were analyzed using generalized Procrustes analysis, hierarchical clustering and thin-plate spline analysis.

The frequency of the palatine torus varies in various populations from different regions of the world. In this study, the change of frequency of palatine torus is examined using 387 skulls from 12 different ancient Anatolian populations in various periods ranging from the Early Bronze Age to the first quarter of the 20th century. While the frequency of palatine torus is 45% in the Early Bronze Age, this ratio steadily increases to 87% in the Ottoman Period and finally declines to 40% during the recent period. It was determined that the increase in the frequency of the palatine torus is statistically significant across different periods from the Early Bronze Age until the 20th century. Constituting a passageway between Asia and Europe and being located on the crossroads of the most important trade route of the Medieval Period, the Silk Road, Anatolia is known to have been subjected to recurring invasions and migrations since the 11th century A.D. Therefore, it is possible to say that, with the introduction of the Mongoloid influence in Anatolia, genetic flow has had a significant role in the observed increase in the frequency of this trait.

It is a fact that researchers make use of various calibration methods for calculating and correcting dental caries frequency. The lack of standardization and accuracy of such methods has made it difficult for the researchers to draw reliable and differentiated conclusions from caries frequencies. Besides, the number of studies on how far the calculation methods reflect the "real" caries frequency is very limited. In this study, various methods for calculating caries frequency in skeletal samples are discussed and a new calculation method is proposed for estimating "real" caries frequency. The Hardwick's correction, which is one of the methods discussed in this study, is not successful in estimating "real" caries frequency as it proposes standard values for different life styles and dietary habits. The decayed and missing index is also considered inefficient as it assumes that all antemortem tooth loss is due to caries. The caries correction factor, proposed by Lukacs, achieves more successful results by considering factors other than caries in antemortem tooth loss, but because it does not differentiate between the anterior and posterior tooth groups during calculation, the results to be obtained therefrom may deviate from actual figures. In order to correct any such deviation, the caries correction factor must be applied separately for the anterior and posterior teeth groups since the resistance of each group to cariogenic factors is different. All the methods outlined above do not consider the effects of postmortem tooth loss on caries frequency. As a result, these methods are still far from reflecting a reliable caries frequency. The application of a proportional correction factor--as a technique newly introduced here--corrects the deviation caused by postmortem tooth loss and achieves more realistic results.

The incisors and canines and the premolars and molars show differential resistance to cariogenic factors. The anterior teeth have a lower caries frequency than the posterior teeth. However, these tooth classes are lost differentially in postmortem stages due to their anatomical structures. This differential postmortem tooth loss distorts proportions between the anterior and posterior tooth classes. The disproportionality can affect the calculation of total caries prevalence. In this paper, we propose a new calibration procedure which removes this disproportionality and call it the proportional correction factor. For this procedure, the caries rates of anterior and posterior teeth are corrected by multiplying the anterior teeth by three-eighths and the posterior teeth by five-eighths. These fractions are derived from the human dental formula which contains three anterior and five posterior teeth by side. The correction factor is more effective if the proportion of anterior to the posterior teeth is extremely distorted. When this procedure is used with the caries correction factor, it provides a useful way to approach to an almost true caries prevalence.