Paleogenomic Data Research Articles

Clubfoot and its implications for the locomotion of a medieval skeleton from Estremoz, Portugal

This study describes foot bone anomalies and the degenerative changes associated with locomotion adaptations. An adult male (approximately 29-46 years old) from Estremoz, Portugal (13th-15th century). The skeletal anomalies observed in this skeleton were described and measurements were compared between both sides of the individual and with the mean of the adult males from the same collection. The most anomalous bones are the right medial cuneiform and metatarsals. Degenerative changes are more severe on the left lower limb and right upper limb. This skeleton represents a unilateral case of talipes varus of the right foot, with the metatarsals being more affected while previously published cases show more severe anomalies of the hindfoot. The degenerative changes observed in the skeleton suggest that both legs and arms, aided by crutches, were used for locomotion. This case shows that club foot skeletal anomalies are variable and the pattern of bony changes throughout the body can reveal locomotion adaptations. The possibility of a genetic cause cannot be assessed due to the absence of paleogenomic data. Since the anomalies found in this case are different than those previously published, we recommend care when analysing foot bones.

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

Human culture, biology, and health were shaped dramatically by the onset of agriculture ∼12,000 y B.P. This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared “predicted” genetic contributions to height from paleogenomic data and “achieved” adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (∼38,000 to 2,400 B.P.). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P = 0.040) and −2.21 cm shorter relative to post-Neolithic individuals (P = 0.068), with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation: for example, with Neolithic individuals −2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P = 0.120). We also incorporated observations of paleopathological indicators of nonspecific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

Genomic basis for skin phenotype and cold adaptation in the extinct Steller's sea cow.

Steller’s sea cow, an extinct sirenian and one of the largest Quaternary mammals, was described by Georg Steller in 1741 and eradicated by humans within 27 years. Here, we complement Steller’s descriptions with paleogenomic data from 12 individuals. We identified convergent evolution between Steller’s sea cow and cetaceans but not extant sirenians, suggesting a role of several genes in adaptation to cold aquatic (or marine) environments. Among these are inactivations of lipoxygenase genes, which in humans and mouse models cause ichthyosis, a skin disease characterized by a thick, hyperkeratotic epidermis that recapitulates Steller’s sea cows’ reportedly bark-like skin. We also found that Steller’s sea cows’ abundance was continuously declining for tens of thousands of years before their description, implying that environmental changes also contributed to their extinction.

Genomic Analysis of 18th-Century Kazakh Individuals and Their Oral Microbiome.

Simple SummaryPaleogenomic research has enhanced our understanding of past human populations and migrations. Moreover, ancient DNA can also provide information on the interactions between humans and their associated pathogens. Periodontitis, currently suffered by millions of people worldwide, is a gum infection that is caused by pathogenic oral bacteria, widely referred to as the “red complex”, which can lead to tooth loss and has been linked to an increased risk of oesophageal cancer. In this study we combine human population genetics with genomic analysis of the oral microbiome of 18th-century people from the Kazakh Khanate in Kazakhstan to gain insight into their health status and explore bacterial coadaptation to recent dietary changes.The Asian Central Steppe, consisting of current-day Kazakhstan and Russia, has acted as a highway for major migrations throughout history. Therefore, describing the genetic composition of past populations in Central Asia holds value to understanding human mobility in this pivotal region. In this study, we analyse paleogenomic data generated from five humans from Kuygenzhar, Kazakhstan. These individuals date to the early to mid-18th century, shortly after the Kazakh Khanate was founded, a union of nomadic tribes of Mongol Golden Horde and Turkic origins. Genomic analysis identifies that these individuals are admixed with varying proportions of East Asian ancestry, indicating a recent admixture event from East Asia. The high amounts of DNA from the anaerobic Gram-negative bacteria Tannerella forsythia, a periodontal pathogen, recovered from their teeth suggest they may have suffered from periodontitis disease. Genomic analysis of this bacterium identified recently evolved virulence and glycosylation genes including the presence of antibiotic resistance genes predating the antibiotic era. This study provides an integrated analysis of individuals with a diet mostly based on meat (mainly horse and lamb), milk, and dairy products and their oral microbiome.

Susceptibility to Neurodegenerative Disorders: Insights from Paleogenomic Data

abstract: Ancient human genome data accumulated in recent years can be employed to establish the spatiotemporal trajectories of genetic variants associated with human diseases. Such knowledge might illuminate if and how past adaptations impact contemporary human health and medicine. Scarcely any studies have yet attempted to evaluate genetic susceptibility to neurodegenerative disorders in ancient human communities. Using publicly available ancient human genome-wide data, this study evaluated the molecular predisposition to neurodegenerative disorders in ancient human communities. Ancient genome-wide data was screened for the presence of variants unequivocally associated with neuro-degenerative disorders in modern populations, identifying two rare variants in the LRRK2 gene associated with Mendelian Parkinson’s disease, a pathogenic variant in the CRH gene associated with an uncommon form of epilepsy, and a rare variant in the TREM2 gene that is a possible risk modifier associated with Alzheimer’s disease. Their historical and geographic prevalence was also assessed, indicating differing spatiotemporal frequency dynamics for these clinically significant variants. Neurodegenerative disorders often have poorly understood pathogenesis that might be elucidated by studying the interaction of past genetic variability with ecological and evolutionary factors such as adverse environmental conditions, specific selective pressures, periods of population isolation, and admixture processes. Data on molecular predisposition to neurodegenerative disorders in ancient genomes is instructive to modern medical diagnostic and therapeutic practices.

Diversity and Structure of Mitochondrial Gene Pools of Slavs in the Ethnogenetic Aspect

Data on the variability of the nucleotide sequences of whole mitochondrial genomes in populations of Russians, Poles, and Serbs, which represent, respectively, the groups of East, West, and South Slavs, are reviewed in comparison with similar data for other European peoples. It was shown that the results of the analysis of the variability of whole mitogenomes make it possible to substantially detail the ideas about the structure and diversity of mitochondrial gene pools obtained earlier with other approaches, e.g., analysis of the distribution of haplotypes of mtDNA major noncoding region or the frequencies of mitochondrial haplogroups. It has been demonstrated that Bayesian analysis of large data sets on the variability of whole mitogenomes in the Slavs enabled the identification of between-regional differences in the dynamics of the effective population size over time for Europe. The use of a phylogeographic analysis of modern and paleogenomic data on the variability of whole mitogenomes makes it possible to define unique phylogenetic mtDNA clusters specific to certain ethnic groups and their communities. Their common genetic origin, which dates back to the Bronze and Iron Ages, is demonstrated on the example of three ethnic groups of Slavs.

Genetic markers on the distribution of ancient marine hunters in Priokhotye

Представлен обзор сведений о генетическом полиморфизме современного и древнего населения Севера Азии и Америки с целью реконструкции истории миграций древних морских охотников в Охотоморском регионе. Проанализированы данные о полиморфизме митохондриальной ДНК и распространенности «арктиче- ской» мутации – варианта rs80356779-A гена CPT1A. Известно, что «арктический» вариант гена CPT1A с высокой частотой распространен в современных популяциях эскимосов, чукчей, коряков и других народов Охотоморско- го региона, хозяйственный уклад которых связан с морским зверобойным промыслом. Согласно палеогеномным данным, самые ранние находки «арктического» варианта гена CPT1A обнаружены у гренландских и канадских па- леоэскимосов (4 тыс. лет назад), представителей токаревской культуры Северного Приохотья (3 тыс. лет назад) и носителей культуры позднего дзёмона острова Хоккайдо (3.5–3.8 тыс. лет назад). Результаты анализа позволили выявить несколько миграционных событий, связанных с распространением морских охотников в Охотоморском регионе. Самая поздняя миграция, оставившая следы у носителей культуры эпи-дзёмон (2.0–2.5 тыс. лет назад), привнесла с севера Приохотья на Хоккайдо и соседние территории Приамурья митохондриальную гаплогруппу G1b и «арктический» вариант гена CPT1A. Следы более ранней миграции, также привнесшей «арктическую» мута- цию, зарегистрированы у населения позднего дзёмона Хоккайдо (3.5–3.8 тыс. лет назад). Проведен филогенети- ческий анализ митохондриальных геномов, относящихся к редкой гаплогруппе C1a, встречающейся у населения Дальнего Востока и Японии, но в филогенетическом отношении родственной C1-гаплогруппам американских индейцев. Результаты показали, что дивергенция митохондриальных линий в пределах гаплогруппы C1a проис- ходила в диапазоне от 7.9 до 6.6 тыс. лет назад, а возраст японской ветви гаплогруппы C1a составляет ~5.2 тыс. лет. Пока неизвестно, связана ли эта миграция с распространением «арктического» варианта гена CPT1A или же присутствие C1a-гаплотипов у населения островов Японии маркирует собой еще один, более ранний, эпизод миграционной истории, связывающей население северо-западной Пацифики и Северной Америки.

Inference of natural selection from ancient DNA.

Evolutionary processes, including selection, can be indirectly inferred based on patterns of genomic variation among contemporary populations or species. However, this often requires unrealistic assumptions of ancestral demography and selective regimes. Sequencing ancient DNA from temporally spaced samples can inform about past selection processes, as time series data allow direct quantification of population parameters collected before, during, and after genetic changes driven by selection. In this Comment and Opinion, we advocate for the inclusion of temporal sampling and the generation of paleogenomic datasets in evolutionary biology, and highlight some of the recent advances that have yet to be broadly applied by evolutionary biologists. In doing so, we consider the expected signatures of balancing, purifying, and positive selection in time series data, and detail how this can advance our understanding of the chronology and tempo of genomic change driven by selection. However, we also recognize the limitations of such data, which can suffer from postmortem damage, fragmentation, low coverage, and typically low sample size. We therefore highlight the many assumptions and considerations associated with analyzing paleogenomic data and the assumptions associated with analytical methods.

Reconstructing protein-coding sequences from ancient DNA.

Obtaining information about functional details of proteins of extinct species is of critical importance for a better understanding of the real-life appearance, behavior and ecology of these lost entries in the book of life. In this chapter, we discuss the possibilities to retrieve the necessary DNA sequence information from paleogenomic data obtained from fossil specimens, which can then be used to express and subsequently analyze the protein of interest. We discuss the problems specific to ancient DNA, including miscoding lesions, short read length and incomplete paleogenome assemblies. Finally, we discuss an alternative, but currently rarely used approach, direct PCR amplification, which is especially useful for comparatively short proteins.

Sources of the mitochondrial gene pool of Russians by the results of analysis of modern and paleogenomic data

Paleogenomic studies of recent years have shown that the Bronze Age migrations of populations of the PontoCaspian steppes from the east to the west of Europe had a great influence on the formation of the genetic makeup of modern Europeans. The results of studies of the variability of mitochondrial genomes in the modern Russian populations of Eastern Europe also made it possible to identify an increase in the effective population size during the Bronze Age, which, apparently, could be related to the migration processes of this time. This paper presents the results of analysis of data on the variability of entire mitochondrial genomes in the modern Russian populations in comparison with the distribution of mtDNA haplogroups in the ancient populations of Europe and the Caucasus of the Neolithic and Bronze Age. It was shown that the formation of the modern appearance of the Russian mitochondrial gene pool began approximately 4 thousand years B.C. due to the influx of mtDNA haplotypes characteristic of the population of Central and Western Europe to the east of Europe. It is assumed that the migrations of the ancient populations of the Ponto-Caspian steppes in the western direction led to the formation of mixed populations in Central Europe, bearing mitochondrial haplogroups H, J, T, K, W characteristic of Western and Central Europeans. Further expansion of these populations to the east of Europe and further to Asia explains the emergence of new features of the mitochondrial gene pool in Eastern Europeans. The results of a phylogeographic analysis are also presented, showing that the features of the geographical distribution of the subgroups of the mitochondrial haplogroup R1a in Europe are a reflection of the “Caucasian” component that appeared in the gene pools of various groups of Europeans during the migration of the Bronze Age. The results of phylogeographic analysis of mitochondrial haplogroups U2e2a1d, U4d2, N1a1a1a1, H2b, and H8b1 testify to the migrations of ancient Eastern Europeans to Asia – the south of Siberia and the Indian subcontinent.

Horse Paleogenomes and Human–Animal Interactions in Prehistory

A new analysis of paleogenomic data from 278 ancient horses (Fages et al. Cellhttp://doi.org/10.1016/j.cell.2019.03.049) finds that this animal - crucially important to many ancient and contemporary human societies for subsistence, transportation, conflict, and more - was domesticated in at least two different regions, but with the geographic and cultural origins of the modern domestic horse lineage remaining unknown. By tracing ancient horse population movements and inferring the spatiotemporal trajectories of phenotypic adaptations, this study provides fresh perspectives on past human group interactions and activities.

Megalithic tombs in western and northern Neolithic Europe were linked to a kindred society

Paleogenomic and archaeological studies show that Neolithic lifeways spread from the Fertile Crescent into Europe around 9000 BCE, reaching northwestern Europe by 4000 BCE. Starting around 4500 BCE, a new phenomenon of constructing megalithic monuments, particularly for funerary practices, emerged along the Atlantic façade. While it has been suggested that the emergence of megaliths was associated with the territories of farming communities, the origin and social structure of the groups that erected them has remained largely unknown. We generated genome sequence data from human remains, corresponding to 24 individuals from five megalithic burial sites, encompassing the widespread tradition of megalithic construction in northern and western Europe, and analyzed our results in relation to the existing European paleogenomic data. The various individuals buried in megaliths show genetic affinities with local farming groups within their different chronological contexts. Individuals buried in megaliths display (past) admixture with local hunter-gatherers, similar to that seen in other Neolithic individuals in Europe. In relation to the tomb populations, we find significantly more males than females buried in the megaliths of the British Isles. The genetic data show close kin relationships among the individuals buried within the megaliths, and for the Irish megaliths, we found a kin relation between individuals buried in different megaliths. We also see paternal continuity through time, including the same Y-chromosome haplotypes reoccurring. These observations suggest that the investigated funerary monuments were associated with patrilineal kindred groups. Our genomic investigation provides insight into the people associated with this long-standing megalith funerary tradition, including their social dynamics.

The Northern Dispersal Route

Archaeological evidence indicates that the original settlement of the Altai occurred by ∼800 ka. The next major wave of hominin migration occurred by approximately 500–400 ka, followed by another one at ∼300 ka. Archaeological findings indicate a continuous evolution of lithic industries between 80 and 10 ka across the Altai. At about 55–45 ka, a small group of Neanderthals appeared in the Altai, producing various forms of lithics at places such as Okladnikov Cave and Chagyrskaya Cave. In the case of Denisova Cave, we suggest that the probable assimilation of Neanderthals occurred without any significant changes in material culture. The current archaeological patterns are well matched with the paleogenomic data from the region. Genetic data suggest that Denisovans were present in the area during at least two separate occasions and over a long period of time, with their presence perhaps interrupted by Neanderthal occupation. The analysis of odontological data shows that Denisovans preserved some archaic morphological features. The archaeological data, along with fragmentary human remains, demonstrate significantly different patterns in comparison with contemporary sites in eastern Asia. The specific position of the Denisovans could possibly be explained as a result of the temporal and geographic isolation of the migrant groups over a long period of time, with the ancestral population originating from western Asia.

Genomic fossils reveal adaptation of non-autonomous pararetroviruses driven by concerted evolution of noncoding regulatory sequences.

The interplay of different virus species in a host cell after infection can affect the adaptation of each virus. Endogenous viral elements, such as endogenous pararetroviruses (PRVs), have arisen from vertical inheritance of viral sequences integrated into host germline genomes. As viral genomic fossils, these sequences can thus serve as valuable paleogenomic data to study the long-term evolutionary dynamics of virus–virus interactions, but they have rarely been applied for this purpose. All extant PRVs have been considered autonomous species in their parasitic life cycle in host cells. Here, we provide evidence for multiple non-autonomous PRV species with structural defects in viral activity that have frequently infected ancient grass hosts and adapted through interplay between viruses. Our paleogenomic analyses using endogenous PRVs in grass genomes revealed that these non-autonomous PRV species have participated in interplay with autonomous PRVs in a possible commensal partnership, or, alternatively, with one another in a possible mutualistic partnership. These partnerships, which have been established by the sharing of noncoding regulatory sequences (NRSs) in intergenic regions between two partner viruses, have been further maintained and altered by the sequence homogenization of NRSs between partners. Strikingly, we found that frequent region-specific recombination, rather than mutation selection, is the main causative mechanism of NRS homogenization. Our results, obtained from ancient DNA records of viruses, suggest that adaptation of PRVs has occurred by concerted evolution of NRSs between different virus species in the same host. Our findings further imply that evaluation of within-host NRS interactions within and between populations of viral pathogens may be important.

Early farmers from across Europe directly descended from Neolithic Aegeans

Farming and sedentism first appeared in southwestern Asia during the early Holocene and later spread to neighboring regions, including Europe, along multiple dispersal routes. Conspicuous uncertainties remain about the relative roles of migration, cultural diffusion, and admixture with local foragers in the early Neolithization of Europe. Here we present paleogenomic data for five Neolithic individuals from northern Greece and northwestern Turkey spanning the time and region of the earliest spread of farming into Europe. We use a novel approach to recalibrate raw reads and call genotypes from ancient DNA and observe striking genetic similarity both among Aegean early farmers and with those from across Europe. Our study demonstrates a direct genetic link between Mediterranean and Central European early farmers and those of Greece and Anatolia, extending the European Neolithic migratory chain all the way back to southwestern Asia.

Genomic Data from Extinct North American Camelops Revise Camel Evolutionary History.

Recent advances in paleogenomic technologies have enabled an increasingly detailed understanding of the evolutionary relationships of now-extinct mammalian taxa. However, a number of enigmatic Quaternary species have never been characterized with molecular data, often because available fossils are rare or are found in environments that are not optimal for DNA preservation. Here, we analyze paleogenomic data extracted from bones attributed to the late Pleistocene western camel, Camelops cf. hesternus, a species that was distributed across central and western North America until its extinction approximately 13,000 years ago. Despite a modal sequence length of only around 35 base pairs, we reconstructed high-coverage complete mitochondrial genomes and low-coverage partial nuclear genomes for each specimen. We find that Camelops is sister to African and Asian bactrian and dromedary camels, to the exclusion of South American camelids (llamas, guanacos, alpacas, and vicuñas). These results contradict previous morphology-based phylogenetic models for Camelops, which suggest instead a closer relationship between Camelops and the South American camelids. The molecular data imply a Late Miocene divergence of the Camelops clade from lineages that separately gave rise to the extant camels of Eurasia. Our results demonstrate the increasing capacity of modern paleogenomic methods to resolve evolutionary relationships among distantly related lineages.

Modern humans' paleogenomics and the new evidences on the European prehistory

The modern human settlement of Europe is a complex process with overimposed migrations and regionalisation episodes, as well as adaptive processes that shaped the genome of modern populations. New developments in massive sequencing techniques allow now the generation of an unprecedented amount of genomic data, including the genotyping of a large number of single nucleotide polymorphisms (SNPs) and the generation of complete ancient genomes. These paleogenomic data will have much more resolution for studying the past than genomic data from present-day individuals because migration, admixture and population replacement can confound the interpretation of current genetic diversity. However, their interpretation will require a real multidisciplinary effort, involving population geneticists, archaeologists and anthropologists. Here, we explain how paleogenomics is providing new insights into a wide range of topics such as demography, undetected migrations, mating strategies or adaptive processes of prehistoric European populations.Statement of significance The study of the prehistoric modern humans' settlement of Europe has been until recently restricted to fields such as archaeology and physical anthropology. However, with the advent of the new sequencing technologies in the last few years, it is increasingly possible to retrieve massive genomic data from these past populations, and to directly test previous hypothesis on human population movements and affinities. We provide here a guideline of the main areas of study of the past that will likely be impacted by paleogenomic studies in the next years.Data availability The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are contained within the paper.

A Paleogenomic Perspective on Evolution and Gene Function: New Insights from Ancient DNA

The publication of partial and complete paleogenomes within the last few years has reinvigorated research in ancient DNA. No longer limited to short fragments of mitochondrial DNA, inference of evolutionary processes through time can now be investigated from genome-wide data sampled as far back as 700,000 years. Tremendous insights have been made, in particular regarding the hominin lineage. With rare exception, however, a paleogenomic perspective has been mired by the quality and quantity of recoverable DNA. Though conceptually simple, extracting ancient DNA remains challenging, and sequencing ancient genomes to high coverage remains prohibitively expensive for most laboratories. Still, with improvements in DNA isolation and declining sequencing costs, the taxonomic and geographic purview of paleogenomics is expanding at a rapid pace. With improved capacity to screen large numbers of samples for those with high proportions of endogenous ancient DNA, paleogenomics is poised to become a key technology to better understand recent evolutionary events.

Paleogenomic data suggest mammal‐like genome size in the ancestral amniote and derived large genome size in amphibians

An unsolved question in evolutionary genomics is whether amniote genomes have been expanding or contracting since the common ancestor of this diverse group. Here, we report on the polarity of amniote genome size evolution using genome size estimates for 14 extinct tetrapod genera from the Paleozoic and early Mesozoic Eras using osteocyte lacunae size as a correlate. We find substantial support for a phylogenetically controlled regression model relating genome size to osteocyte lacunae size (P of slopes <0.01, r²=0.65, phylogenetic signal λ=0.83). Genome size appears to have been homogeneous across Paleozoic crown-tetrapod lineages (average haploid genome size 2.9-3.7 pg) with values similar to those of extant mammals. The differentiation in genome size and underlying architecture among extant tetrapod lineages likely evolved in the Mesozoic and Cenozoic Eras, with expansion in amphibians, contractions along the diapsid lineage, and no directional change within the synapsid lineage leading to mammals.