Showing papers by "David Reich published in 2022"

Ancient DNA and deep population structure in sub-Saharan African foragers

Abstract: Abstract Multiple lines of genetic and archaeological evidence suggest that there were major demographic changes in the terminal Late Pleistocene epoch and early Holocene epoch of sub-Saharan Africa 1–4 . Inferences about this period are challenging to make because demographic shifts in the past 5,000 years have obscured the structures of more ancient populations 3,5 . Here we present genome-wide ancient DNA data for six individuals from eastern and south-central Africa spanning the past approximately 18,000 years (doubling the time depth of sub-Saharan African ancient DNA), increase the data quality for 15 previously published ancient individuals and analyse these alongside data from 13 other published ancient individuals. The ancestry of the individuals in our study area can be modelled as a geographically structured mixture of three highly divergent source populations, probably reflecting Pleistocene interactions around 80–20 thousand years ago, including deeply diverged eastern and southern African lineages, plus a previously unappreciated ubiquitous distribution of ancestry that occurs in highest proportion today in central African rainforest hunter-gatherers. Once established, this structure remained highly stable, with limited long-range gene flow. These results provide a new line of genetic evidence in support of hypotheses that have emerged from archaeological analyses but remain contested, suggesting increasing regionalization at the end of the Pleistocene epoch.

On the limits of fitting complex models of population history to genetic data

Abstract: Our understanding of human population history in deep time has been assisted by fitting “admixture graphs” to data: models that specify the ordering of population splits and mixtures which is the only information needed to capture the patterns of allele frequency correlation among populations. Not needing to specify population size changes, split times, or whether admixture events were sudden or drawn out simplifies the space of models that need to be searched. However, the space of possible admixture graphs relating populations is vast and cannot be sampled fully, and thus most published studies have identified fitting admixture graphs through a manual process driven by prior hypotheses, leaving the vast majority of alternative models unexplored. Here, we develop a method for systematically searching the space of all admixture graphs that can incorporate non-genetic information in the form of topology constraints. We implement this findGraphs tool within a software package, ADMIXTOOLS 2, which is a reimplementation of the ADMIXTOOLS software with new features and large performance gains. We apply this methodology to identify alternative models to admixture graphs that played key roles in eight published studies and find that graphs modeling more than six populations and two or three admixture events are often not unique, with many alternative models fitting nominally or significantly better than the published one. Our results suggest that strong claims about population history from admixture graphs should only be made when all well-fitting and temporally plausible models share common topological features. Our re-evaluation of published data also provides insight into the population histories of humans, dogs, and horses, identifying features that are stable across the models we explored, as well as scenarios of populations relationships that differ in important ways from models that have been highlighted in the literature, that fit the allele frequency correlation data, and that are not obviously wrong.

The genetic history of the Southern Arc: A bridge between West Asia and Europe

Abstract: By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra–West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe. Description Connecting genes and history Stories about the peopling—and people—of Southern Europe and West Asia have been passed down for thousands of years, and these stories have contributed to our historical understanding of populations. Genomic data provide the opportunity to truly understand these patterns independently from written history. In a trio of papers, Lazaridis et al. examined more than 700 ancient genomes from across this region, the Southern Arc, spanning 11,000 years, from the earliest farming cultures to post-Medieval times (see the Perspective by Arbuckle and Schwandt). On the basis of these results, the authors suggest that earlier reliance on modern phenotypes and ancient writings and artistic depictions provided an inaccurate picture of early Indo-Europeans, and they provide a revised history of the complex migrations and population integrations that shaped these cultures. —SNV A web of migrations between Anatolia, its neighbors, and the Steppe suggests a West Asian origin of Indo-Anatolian languages. INTRODUCTION For thousands of years, humans moved across the “Southern Arc,” the area bridging Europe through Anatolia with West Asia. We report ancient DNA data from 727 individuals of this region over the past 11,000 years, which we co-analyzed with the published archaeogenetic record to understand the origins of its people. We focused on the Chalcolithic and Bronze Ages about 7000 to 3000 years ago, when Indo-European language speakers first appeared. RATIONALE Genetic data are relevant for understanding linguistic evolution because they can identify movement-driven opportunities for language spread. We investigated how the changing ancestral landscape of the Southern Arc, as reflected in DNA, corresponds to the structure inferred by linguistics, which links Anatolian (e.g., Hittite and Luwian) and Indo-European (e.g., Greek, Armenian, Latin, and Sanskrit) languages as twin daughters of a Proto-Indo-Anatolian language. RESULTS Steppe pastoralists of the Yamnaya culture initiated a chain of migrations linking Europe in the west to China and India in the East. Some people across the Balkans (about 5000 to 4500 years ago) traced almost all their genes to this expansion. Steppe migrants soon admixed with locals, creating a tapestry of diverse ancestry from which speakers of the Greek, Paleo-Balkan, and Albanian languages arose. The Yamnaya expansion also crossed the Caucasus, and by about 4000 years ago, Armenia had become an enclave of low but pervasive steppe ancestry in West Asia, where the patrilineal descendants of Yamnaya men, virtually extinct on the steppe, persisted. The Armenian language was born there, related to Indo-European languages of Europe such as Greek by their shared Yamnaya heritage. Neolithic Anatolians (in modern Turkey) were descended from both local hunter-gatherers and Eastern populations of the Caucasus, Mesopotamia, and the Levant. By about 6500 years ago and thereafter, Anatolians became more genetically homogeneous, a process driven by the flow of Eastern ancestry across the peninsula. Earlier forms of Anatolian and non–Indo-European languages such as Hattic and Hurrian were likely spoken by migrants and locals participating in this great mixture. Anatolia is remarkable for its lack of steppe ancestry down to the Bronze Age. The ancestry of the Yamnaya was, by contrast, only partly local; half of it was West Asian, from both the Caucasus and the more southern Anatolian-Levantine continuum. Migration into the steppe started by about 7000 years ago, making the later expansion of the Yamnaya into the Caucasus a return to the homeland of about half their ancestors. CONCLUSION All ancient Indo-European speakers can be traced back to the Yamnaya culture, whose southward expansions into the Southern Arc left a trace in the DNA of the Bronze Age people of the region. However, the link connecting the Proto-Indo-European–speaking Yamnaya with the speakers of Anatolian languages was in the highlands of West Asia, the ancestral region shared by both. Many partings, many meetings: How migration and admixture drove early language spread. Westward and northward migrations out of the West Asian highlands split the Proto-Indo-Anatolian language into Anatolian and Indo-European branches. Yamnaya pastoralists, formed on the steppe by a fusion of newcomers and locals, admixed again as they expanded far and wide, splitting the Proto-Indo-European language into its daughter languages across Eurasia. Border colors represent the ancestry and locations of five source populations before the migrations (arrows) and mixture (pie charts) documented here.

An integrative skeletal and paleogenomic analysis of stature variation suggests relatively reduced health for early European farmers

Abstract: Significance Subsistence shifts from hunting and gathering to agriculture over the last 12,000 y have impacted human culture, biology, and health. Although past human health cannot be assessed directly, adult stature variation and skeletal indicators of nonspecific stress can serve as proxies for health during growth and development. By integrating paleogenomic genotype and osteological stature data on a per-individual basis for 167 prehistoric Europeans, we observe relatively shorter than expected statures among early farmers after correcting for individual genetic contributions to stature. Poorer nutrition and/or increased disease burdens for early agriculturalists may partly underscore this result. Our integrated osteological–genetic model has exciting potential for studies of past human health and expansion into various other contexts.

South-to-north migration preceded the advent of intensive farming in the Maya region

Abstract: The genetic prehistory of human populations in Central America is largely unexplored leaving an important gap in our knowledge of the global expansion of humans. We report genome-wide ancient DNA data for a transect of twenty individuals from two Belize rock-shelters dating between 9,600-3,700 calibrated radiocarbon years before present (cal. BP). The oldest individuals (9,600-7,300 cal. BP) descend from an Early Holocene Native American lineage with only distant relatedness to present-day Mesoamericans, including Mayan-speaking populations. After ~5,600 cal. BP a previously unknown human dispersal from the south made a major demographic impact on the region, contributing more than 50% of the ancestry of all later individuals. This new ancestry derived from a source related to present-day Chibchan speakers living from Costa Rica to Colombia. Its arrival corresponds to the first clear evidence for forest clearing and maize horticulture in what later became the Maya region.

The Anglo-Saxon migration and the formation of the early English gene pool

Abstract: Abstract The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture 1 . The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate 2–4 . Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans—including 278 individuals from England—alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present-day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age France 5,6 .

Evaluation and validation of an RT‐PCR assay for specific detection of monkeypox virus (MPXV)

Abstract: Monkeypox virus (MPXV) is a zoonotic orthopoxvirus within the Poxviridae family. MPXV is endemic to Central and West Africa. However, the world is currently witnessing an international outbreak with no clear epidemiological links to travel or animal exposure and with ever‐increasing numbers of reported cases worldwide. Here, we evaluated and validated a new, sensitive, and specific real‐time PCR‐assay for MPXV diagnosis in humans and compare the performance of this novel assay against a Food & Drug Administration‐cleared pan‐Orthopox RT‐PCR assay. We determined specificity, sensitivity, and analytic performance of the PKamp™ Monkeypox Virus RT‐PCR assay targeting the viral F3L‐gene. In addition, we further evaluated MPXV‐PCR‐positive specimens by viral culture, electron microscopy, and viral inactivation assays. The limit of detection was established at 7.2 genome copies/reaction, and MPXV was successfully identified in 20 clinical specimens with 100% correlation against the reference method with 100% sensitivity and specificity. Our results demonstrated the validity of this rapid, robust, and reliable RT‐PCR assay for specific and accurate diagnosis of MPXV infection in human specimens collected both as dry swabs and in viral transport media. This assay has been approved by NYS Department of Health for clinical use.

Three assays for in-solution enrichment of ancient human DNA at more than a million SNPs

Abstract: The strategy of in-solution enrichment for hundreds of thousands of single-nucleotide polymorphisms (SNPs) has been used to analyze >70% of individuals with genome-scale ancient DNA published to date. This approach makes it economical to study ancient samples with low proportions of human DNA and increases the rate of conversion of sampled remains into interpretable data. So far, nearly all such data have been generated using a set of bait sequences targeting about 1.24 million SNPs (the “1240k reagent”), but synthesis of the reagent has been cost-effective for only a few laboratories. In 2021, two companies, Daicel Arbor Biosciences and Twist Bioscience, made available assays that target the same core set of SNPs along with supplementary content. We test all three assays on a common set of 27 ancient DNA libraries and show that all three are effective at enriching many hundreds of thousands of SNPs. For all assays, one round of enrichment produces data that are as useful as two. In our testing, the “Twist Ancient DNA” assay produces the highest coverages, greatest uniformity on targeted positions, and almost no bias toward enriching one allele more than another relative to shotgun sequencing. We also identify hundreds of thousands of targeted SNPs for which there is minimal allelic bias when comparing 1240k data to either shotgun or Twist data. This facilitates coanalysis of the large data sets that have been generated using 1240k and Twist capture, as well as shotgun sequencing approaches.

The diverse genetic origins of a Classical period Greek army

Abstract: Significance By studying genome-wide data from 54 individuals from eighth- to fifth-century Sicily, we gain insights into the composition of Classical Greek armies (ca. fifth c. BCE) and the populace of a Greek colony. The presence of mercenaries in Greek armies fighting in the Mediterranean, as early as 480 BCE and with origins as far away as northern Europe and the Caucasus, is absent from historical texts and thus so far underappreciated in ancient classical scholarship. Our interdisciplinary study both underlines the value of integrating genetic studies to complement archaeological and historical research and highlights the importance of warfare in facilitating continental-scale human mobility, cultural contact, and cooperation in the Mediterranean of the Classical period.

Three Reagents for in-Solution Enrichment of Ancient Human DNA at More than a Million SNPs

Abstract: In-solution enrichment for hundreds of thousands of single nucleotide polymorphisms (SNPs) has been the source of >70% of all genome-scale ancient human DNA data published to date. This approach has made it possible to generate data for one to two orders of magnitude lower cost than random shotgun sequencing, making it economical to study ancient samples with low proportions of human DNA, and increasing the rate of conversion of sampled remains into working data thereby facilitating ethical stewardship of human remains. So far, nearly all ancient DNA data obtained using in-solution enrichment has been generated using a set of bait sequences targeting about 1.24 million SNPs (the ‘1240k reagent’). These sequences were published in 2015, but synthesis of the reagent has been cost-effective for only a few laboratories. In 2021, two companies made available reagents that target the same core set of SNPs along with supplementary content. Here, we test the properties of the three reagents on a common set of 27 ancient DNA libraries across a range of richness of DNA content and percentages of human molecules. All three reagents are highly effective at enriching many hundreds of thousands of SNPs. For all three reagents and a wide range of conditions, one round of enrichment produces data that is as useful as two rounds when tens of millions of sequences are read out as is typical for such experiments. In our testing, the “Twist Ancient DNA” reagent produces the highest coverages, greatest uniformity on targeted positions, and almost no bias toward enriching one allele more than another relative to shotgun sequencing. Allelic bias in 1240k enrichment has made it challenging to carry out joint analysis of these data with shotgun data, creating a situation where the ancient DNA community has been publishing two important bodes of data that cannot easily be co-analyzed by population genetic methods. To address this challenge, we introduce a subset of hundreds of thousands of SNPs for which 1240k data can be effectively co-analyzed with all other major data types.

A genetic probe into the ancient and medieval history of Southern Europe and West Asia

Abstract: Literary and archaeological sources have preserved a rich history of Southern Europe and West Asia since the Bronze Age that can be complemented by genetics. Mycenaean period elites in Greece did not differ from the general population and included both people with some steppe ancestry and others, like the Griffin Warrior, without it. Similarly, people in the central area of the Urartian Kingdom around Lake Van lacked the steppe ancestry characteristic of the kingdom’s northern provinces. Anatolia exhibited extraordinary continuity down to the Roman and Byzantine periods, with its people serving as the demographic core of much of the Roman Empire, including the city of Rome itself. During medieval times, migrations associated with Slavic and Turkic speakers profoundly affected the region. Description Connecting genes and history Stories about the peopling—and people—of Southern Europe and West Asia have been passed down for thousands of years, and these stories have contributed to our historical understanding of populations. Genomic data provide the opportunity to truly understand these patterns independently from written history. In a trio of papers, Lazaridis et al. examined more than 700 ancient genomes from across this region, the Southern Arc, spanning 11,000 years, from the earliest farming cultures to post-Medieval times (see the Perspective by Arbuckle and Schwandt). On the basis of these results, the authors suggest that earlier reliance on modern phenotypes and ancient writings and artistic depictions provided an inaccurate picture of early Indo-Europeans, and they provide a revised history of the complex migrations and population integrations that shaped these cultures. —SNV Polities of the ancient Mediterranean world preserved contrasts of ancestry since the Bronze Age but were linked by migration.

Ancient DNA from Mesopotamia suggests distinct Pre-Pottery and Pottery Neolithic migrations into Anatolia

Abstract: We present the first ancient DNA data from the Pre-Pottery Neolithic of Mesopotamia (Southeastern Turkey and Northern Iraq), Cyprus, and the Northwestern Zagros, along with the first data from Neolithic Armenia. We show that these and neighboring populations were formed through admixture of pre-Neolithic sources related to Anatolian, Caucasus, and Levantine hunter-gatherers, forming a Neolithic continuum of ancestry mirroring the geography of West Asia. By analyzing Pre-Pottery and Pottery Neolithic populations of Anatolia, we show that the former were derived from admixture between Mesopotamian-related and local Epipaleolithic-related sources, but the latter experienced additional Levantine-related gene flow, thus documenting at least two pulses of migration from the Fertile Crescent heartland to the early farmers of Anatolia. Description Connecting genes and history Stories about the peopling—and people—of Southern Europe and West Asia have been passed down for thousands of years, and these stories have contributed to our historical understanding of populations. Genomic data provide the opportunity to truly understand these patterns independently from written history. In a trio of papers, Lazaridis et al. examined more than 700 ancient genomes from across this region, the Southern Arc, spanning 11,000 years, from the earliest farming cultures to post-Medieval times (see the Perspective by Arbuckle and Schwandt). On the basis of these results, the authors suggest that earlier reliance on modern phenotypes and ancient writings and artistic depictions provided an inaccurate picture of early Indo-Europeans, and they provide a revised history of the complex migrations and population integrations that shaped these cultures. —SNV Two pulses of migration appear to have contributed to the early farmers of Anatolia.

1,000 ancient genomes uncover 10,000 years of natural selection in Europe

Abstract: Ancient DNA has revolutionized our understanding of human population history. However, its potential to examine how rapid cultural evolution to new lifestyles may have driven biological adaptation has not been met, largely due to limited sample sizes. We assembled genome-wide data from 1,291 individuals from Europe over 10,000 years, providing a dataset that is large enough to resolve the timing of selection into the Neolithic, Bronze Age, and Historical periods. We identified 25 genetic loci with rapid changes in frequency during these periods, a majority of which were previously undetected. Signals specific to the Neolithic transition are associated with body weight, diet, and lipid metabolism-related phenotypes. They also include immune phenotypes, most notably a locus that confers immunity to Salmonella infection at a time when ancient Salmonella genomes have been shown to adapt to human hosts, thus providing a possible example of human-pathogen co-evolution. In the Bronze Age, selection signals are enriched near genes involved in pigmentation and immune-related traits, including at a key human protein interactor of SARS-CoV-2. Only in the Historical period do the selection candidates we detect largely mirror previously-reported signals, highlighting how the statistical power of previous studies was limited to the last few millennia. The Historical period also has multiple signals associated with vitamin D binding, providing evidence that lactase persistence may have been part of an oligogenic adaptation for efficient calcium uptake and challenging the theory that its adaptive value lies only in facilitating caloric supplementation during times of scarcity. Finally, we detect selection on complex traits in all three periods, including selection favoring variants that reduce body weight in the Neolithic. In the Historical period, we detect selection favoring variants that increase risk for cardiovascular disease plausibly reflecting selection for a more active inflammatory response that would have been adaptive in the face of increased infectious disease exposure. Our results provide an evolutionary rationale for the high prevalence of these deadly diseases in modern societies today and highlight the unique power of ancient DNA in elucidating biological change that accompanied the profound cultural transformations of recent human history.

Obesity as a mortality risk factor in the medical ward: a case control study

Abstract: Research regarding the association between severe obesity and in-hospital mortality is inconsistent. We evaluated the impact of body mass index (BMI) levels on mortality in the medical wards. The analysis was performed separately before and during the COVID-19 pandemic.We retrospectively retrieved data of adult patients admitted to the medical wards at the Mount Sinai Health System in New York City. The study was conducted between January 1, 2011, to March 23, 2021. Patients were divided into two sub-cohorts: pre-COVID-19 and during-COVID-19. Patients were then clustered into groups based on BMI ranges. A multivariate logistic regression analysis compared the mortality rate among the BMI groups, before and during the pandemic.Overall, 179,288 patients were admitted to the medical wards and had a recorded BMI measurement. 149,098 were admitted before the COVID-19 pandemic and 30,190 during the pandemic. Pre-pandemic, multivariate analysis showed a "J curve" between BMI and mortality. Severe obesity (BMI > 40) had an aOR of 0.8 (95% CI:0.7-1.0, p = 0.018) compared to the normal BMI group. In contrast, during the pandemic, the analysis showed a "U curve" between BMI and mortality. Severe obesity had an aOR of 1.7 (95% CI:1.3-2.4, p < 0.001) compared to the normal BMI group.Medical ward patients with severe obesity have a lower risk for mortality compared to patients with normal BMI. However, this does not apply during COVID-19, where obesity was a leading risk factor for mortality in the medical wards. It is important for the internal medicine physician to understand the intricacies of the association between obesity and medical ward mortality.

Ancient DNA reveals five streams of migration into Micronesia and matrilocality in early Pacific seafarers

Abstract: Micronesia began to be peopled earlier than other parts of Remote Oceania, but the origins of its inhabitants remain unclear. We generated genome-wide data from 164 ancient and 112 modern individuals. Analysis reveals five migratory streams into Micronesia. Three are East Asian related, one is Polynesian, and a fifth is a Papuan source related to mainland New Guineans that is different from the New Britain–related Papuan source for southwest Pacific populations but is similarly derived from male migrants ~2500 to 2000 years ago. People of the Mariana Archipelago may derive all of their precolonial ancestry from East Asian sources, making them the only Remote Oceanians without Papuan ancestry. Female-inherited mitochondrial DNA was highly differentiated across early Remote Oceanian communities but homogeneous within, implying matrilocal practices whereby women almost never raised their children in communities different from the ones in which they grew up. Description Human migrations into Micronesia The movements of ancient humans can be difficult to ascertain from their current population genetic structure. Studying the peopling of the Micronesian islands, Liu et al. examined 164 ancient human remains from five different archaeological sites in remote Oceania from different prehistoric time frames, along with 112 present-day individuals from the same area. They combined these new data with the results of previous studies and also compared their results with linguistic studies. Their analysis revealed successive movements from island Southeast Asia that differ from those in the southwest Pacific. Furthermore, co-analysis of Micronesian and southwest Pacific ancient DNA indicates that the first people who colonized the Pacific islands had a population structure in which men moved to find their mates, whereas women rarely moved to join men. —LMZ Analyses of ancient and modern Micronesians show different peopling compared with the southwest Pacific

Entwined African and Asian genetic roots of medieval peoples of the Swahili coast

Abstract: Abstract The urban peoples of the Swahili coast traded across eastern Africa and the Indian Ocean and were among the first practitioners of Islam among sub-Saharan people 1,2 . The extent to which these early interactions between Africans and non-Africans were accompanied by genetic exchange remains unknown. Here we report ancient DNA data for 80 individuals from 6 medieval and early modern ( ad 1250–1800) coastal towns and an inland town after ad 1650. More than half of the DNA of many of the individuals from coastal towns originates from primarily female ancestors from Africa, with a large proportion—and occasionally more than half—of the DNA coming from Asian ancestors. The Asian ancestry includes components associated with Persia and India, with 80–90% of the Asian DNA originating from Persian men. Peoples of African and Asian origins began to mix by about ad 1000, coinciding with the large-scale adoption of Islam. Before about ad 1500, the Southwest Asian ancestry was mainly Persian-related, consistent with the narrative of the Kilwa Chronicle, the oldest history told by people of the Swahili coast 3 . After this time, the sources of DNA became increasingly Arabian, consistent with evidence of growing interactions with southern Arabia 4 . Subsequent interactions with Asian and African people further changed the ancestry of present-day people of the Swahili coast in relation to the medieval individuals whose DNA we sequenced.

The Eneolithic cemetery at Khvalynsk on the Volga River

Abstract: Abstract The genetically attested migrations of the third millennium BC have made the origins and nature of the Yamnaya culture a question of broad relevance across northern Eurasia. But none of the key archaeological sites most important for understanding the evolution of Yamnaya culture is published in western languages. These key sites include the fifth-millennium BC Khvalynsk cemetery in the middle Volga steppes. When the first part of the Eneolithic cemetery (Khvalynsk I) was discovered in 1977–1979, the graves displayed many material and ritual traits that were quickly recognized as similar and probably ancestral to Yamnaya customs, but without the Yamnaya kurgans. With the discovery of a second burial plot (Khvalynsk II) 120 m to the south in 1987–1988, Khvalynsk became the largest excavated Eneolithic cemetery in the Don-Volga-Ural steppes (201 recorded graves), dated about 4500–4300 BCE. It has the largest copper assemblage of the fifth millennium BC in the steppes (373 objects) and the largest assemblage of sacrificed domesticated animals (at least 106 sheep-goat, 29 cattle, and 16 horses); and it produced four polished stone maces from well-documented grave contexts. The human skeletons have been sampled extensively for ancient DNA, the basis for an analysis of family relationships. This report compiles information from the relevant Russian-language publications and from the archaeologists who excavated the site, two of whom are co-authors, about the history of excavations, radiocarbon dates, copper finds, domesticated animal sacrifices, polished stone maces, genetic and skeletal studies, and relationships with other steppe cultures as well as agricultural cultures of the North Caucasus (Svobodnoe-Meshoko) and southeastern Europe (Varna and Cucuteni-Tripol’ye B1). Khvalynsk is described as a coalescent culture, integrating and combining northern and southern elements, a hybrid that can be recognized genetically, in cranio-facial types, in exchanged artifacts, and in social segments within the cemetery. Stone maces symbolized the unification and integration of socially defined segments at Khvalynsk.

Ancient DNA from Protohistoric Period Cambodia indicates that South Asians admixed with local populations as early as 1st–3rd centuries CE

Abstract: Abstract Indian cultural influence is remarkable in present-day Mainland Southeast Asia (MSEA), and it may have stimulated early state formation in the region. Various present-day populations in MSEA harbor a low level of South Asian ancestry, but previous studies failed to detect such ancestry in any ancient individual from MSEA. In this study, we discovered a substantial level of South Asian admixture (ca. 40–50%) in a Protohistoric individual from the Vat Komnou cemetery at the Angkor Borei site in Cambodia. The location and direct radiocarbon dating result on the human bone (95% confidence interval is 78–234 calCE) indicate that this individual lived during the early period of Funan, one of the earliest states in MSEA, which shows that the South Asian gene flow to Cambodia started about a millennium earlier than indicated by previous published results of genetic dating relying on present-day populations. Plausible proxies for the South Asian ancestry source in this individual are present-day populations in Southern India, and the individual shares more genetic drift with present-day Cambodians than with most present-day East and Southeast Asian populations.

Haplotype-based inference of recent effective population size in modern and ancient DNA samples

Abstract: Individuals sharing recent ancestors are likely to co-inherit large identical-by-descent (IBD) genomic regions. The distribution of these IBD segments in a population may be used to reconstruct past demographic events such as effective population size variation, but accurate IBD detection is difficult in ancient DNA (aDNA) data and in underrepresented populations with limited reference data. In this work, we introduce an accurate method for inferring effective population size variation during the past ~2,000 years in both modern and aDNA data, called HapNe. HapNe infers recent population size fluctuations using either IBD sharing (HapNe-IBD) or linkage disequilibrium (HapNe-LD), which does not require phasing and can be computed in low coverage data, including data sets with heterogeneous sampling times. HapNe showed improved accuracy in a range of simulated demographic scenarios compared to currently available methods for IBD-based and LD-based inference of recent effective population size, while requiring fewer computational resources. We applied HapNe to several modern populations from the 1, 000 Genomes Project, the UK Biobank, the Allen Ancient DNA Resource, and recently published samples from Iron Age Britain, detecting multiple instances of recent effective population size variation across these groups.

Data and model bias in artificial intelligence for healthcare applications in New Zealand

Abstract: Introduction Developments in Artificial Intelligence (AI) are adopted widely in healthcare. However, the introduction and use of AI may come with biases and disparities, resulting in concerns about healthcare access and outcomes for underrepresented indigenous populations. In New Zealand, Māori experience significant inequities in health compared to the non-Indigenous population. This research explores equity concepts and fairness measures concerning AI for healthcare in New Zealand. Methods This research considers data and model bias in NZ-based electronic health records (EHRs). Two very distinct NZ datasets are used in this research, one obtained from one hospital and another from multiple GP practices, where clinicians obtain both datasets. To ensure research equality and fair inclusion of Māori, we combine expertise in Artificial Intelligence (AI), New Zealand clinical context, and te ao Māori. The mitigation of inequity needs to be addressed in data collection, model development, and model deployment. In this paper, we analyze data and algorithmic bias concerning data collection and model development, training and testing using health data collected by experts. We use fairness measures such as disparate impact scores, equal opportunities and equalized odds to analyze tabular data. Furthermore, token frequencies, statistical significance testing and fairness measures for word embeddings, such as WEAT and WEFE frameworks, are used to analyze bias in free-form medical text. The AI model predictions are also explained using SHAP and LIME. Results This research analyzed fairness metrics for NZ EHRs while considering data and algorithmic bias. We show evidence of bias due to the changes made in algorithmic design. Furthermore, we observe unintentional bias due to the underlying pre-trained models used to represent text data. This research addresses some vital issues while opening up the need and opportunity for future research. Discussions This research takes early steps toward developing a model of socially responsible and fair AI for New Zealand's population. We provided an overview of reproducible concepts that can be adopted toward any NZ population data. Furthermore, we discuss the gaps and future research avenues that will enable more focused development of fairness measures suitable for the New Zealand population's needs and social structure. One of the primary focuses of this research was ensuring fair inclusions. As such, we combine expertise in AI, clinical knowledge, and the representation of indigenous populations. This inclusion of experts will be vital moving forward, proving a stepping stone toward the integration of AI for better outcomes in healthcare.

The lingering effects of Neanderthal introgression on human complex traits

Abstract: The mutations introduced into the ancestors of modern humans from interbreeding with Neanderthals have been suggested to contribute an unexpected extent to complex human traits. However, testing this hypothesis has been challenging due to the idiosyncratic population genetic properties of introgressed mutations. We developed rigorous methods to assess the contribution of introgressed Neanderthal mutations to heritable trait variation relative to that of modern human variants. We applied these methods to analyze 235,592 introgressed Neanderthal mutations and 96 distinct phenotypes measured in about 300,000 unrelated white British individuals in the UK Biobank. Introgressed Neanderthal mutations have a significant contribution to trait variation consistent with the polygenic architecture of complex phenotypes (contributing 0.1% of heritable variation averaged across phenotypes; p = 9.59×10-9). However, the contribution of introgressed mutations tends to be significantly depleted relative to modern human mutations matched for allele frequency and linkage disequilibrium (about 57% depletion on average), consistent with purifying selection on introgressed mutations. Different from previous studies (McArthur 2021), we find no evidence for elevated heritability across the phenotypes examined. We identified 348 independent significant associations of introgressed Neanderthal mutations with 64 phenotypes (p < 1 ×10-10). Previous work (Skov 2021) has suggested that a majority of such associations are likely driven by statistical association with nearby modern human variants that are the true causal variants. We therefore developed a customized statistical fine-mapping methodology for introgressed mutations that led us to identify 112 regions (at a false discovery proportion of 16%) across 47 phenotypes containing 4,303 unique genetic variants where introgressed mutations are highly likely to have a phenotypic effect. Examination of these mutations reveal their substantial impact on genes that are important for the immune system, development, and metabolism. Our results provide the first rigorous basis for understanding how Neanderthal introgression modulates complex trait variation in present-day humans.

Genetic estimates of the initial peopling of Polynesian islands actually reflect later inter-island contacts

Abstract: The timing of the initial peopling of the Polynesian islands remains highly debated. Suggested dates are primarily based on archaeological evidence and differ by several hundred years. Ioannidis et al. [2021] used genome-wide data from 430 modern individuals from 21 Pacific islands to obtain genetic estimates. Their results supported late settlement dates, e.g. approximately 1200 CE for Rapa Nui. However, when investigating the underlying model we found that the genetic estimator used by Ioannidis et al. [2021] is biased to be about 300 years too old. Correcting for this bias gives genetic settlement dates that are more recent than any dates consistent with archaeological records, as radiocarbon dating of human-modified artifacts shows settlement definitively earlier than the bias-corrected genetic estimates. These too-recent estimates can only be explained by substantial gene flow between islands after their initial settlements. Therefore, contacts attested by archaeological and linguistic evidence [Kirch, 2021] must have been accompanied also by demographically significant movement of people. This gene flow well after the initial settlements was not modelled by Ioannidis et al. [2021] and challenges their interpretation that carving anthropomorphic stone statues was spread during initial settlements of islands. Instead, the distribution of this cultural practice likely reflects later inter-island exchanges, as suggested earlier [Kirch, 2017].

Technical Report on Ancient DNA analysis of 27 African Americans from Catoctin Furnace, Maryland

Abstract: Catoctin Furnace is an industrial site that functioned from 1776–1903 and was operated at least partially by an enslaved workforce until about 1850, when it shifted to paid European laborers. A cemetery including 35 graves from which the remains of 32 individuals identified with African ancestry were excavated in 1979-1980 during construction of a highway that impacted the site. Since then, the human remains have been under the stewardship of the Smithsonian’s National Museum of Natural History (NMNH). The goal of this report is to document the successful generation of ancient DNA from 27 individuals from the cemetery. The analysis of the Catoctin individuals is part of a long-term study dedicated to restoring knowledge of the identity, origins, and legacy of the enslaved and free African Americans who labored and were buried at Catoctin Furnace1.

A Bioarchaeological Investigation of Fraternal Stillborn Twins from Tell el-Hesi

Abstract: A double nonadult burial excavated at the Ottoman period (1600–1800 CE) cemetery at Tell el-Hesi was hypothesized to belong to a set of stillborn twins. This study incorporated the use of multiple bioarchaeological techniques in order to assess both the age and survival of the perinates. Cranial and long-bone measurements were undertaken to determine age at death, while stable carbon and nitrogen isotopes were considered alongside microCT assessments of bacterial bioerosion in the cortices of long bones to identify whether these infants were born alive and had breastfed. Ancient DNA analysis can now identify twins with greater certainty and was also employed to confirm the sex and biological relationship between these two individuals. Using these various lines of evidence, we test two hypotheses, ultimately finding support for both: (1) the two perinates buried together from Tell el-Hesi were fraternal female twins; and (2) these perinates were likely stillborn.