La Sassa cave: Isotopic evidence for Copper Age and Bronze Age population dynamics in Central Italy.

This study focuses on the changes in diet and mobility of people buried in the La Sassa cave (Latium, Central Italy) during the Copper and Bronze Ages to contribute to the understanding of the complex contemporary population dynamics in Central Italy. To that purpose, carbon and nitrogen stable isotope analyses, strontium isotope analyses, and FT-IR evaluations were performed on human and faunal remains from this cave. The stable isotope analyses evidence a slight shift in diet between Copper and Bronze Age individuals, which becomes prominent in an individual, dating from a late phase, when the cave was mainly used as a cultic shelter. This diachronic study documents an increased dietary variability due to the introduction of novel resources in these protohistoric societies, possibly related to the southward spread of northern human groups into Central Italy. This contact between different cultures is also testified by the pottery typology found in the cave. The latter shows an increase in cultural intermingling starting during the beginning of the middle Bronze Age. The local mobility during this phase likely involved multiple communities scattered throughout an area of a few kilometers around the cave, which used the latter as a burial site both in the Copper and Bronze ages.

Genomic ancestry, diet and microbiomes of Upper Palaeolithic hunter-gatherers from San Teodoro cave.

Recent improvements in the analysis of ancient biomolecules from human remains and associated dental calculus have provided new insights into the prehistoric diet and genetic diversity of our species. Here we present a multi-omics study, integrating metagenomic and proteomic analyses of dental calculus, and human ancient DNA analysis of the petrous bones of two post-Last Glacial Maximum (LGM) individuals from San Teodoro cave (Italy), to reconstruct their lifestyle and the post-LGM resettlement of Europe. Our analyses show genetic homogeneity in Sicily during the Palaeolithic, representing a hitherto unknown Italian genetic lineage within the previously identified Villabruna cluster. We argue that this lineage took refuge in Italy during the LGM, followed by a subsequent spread to central-western Europe. Analysis of dental calculus showed a diet rich in animal proteins which is also reflected on the oral microbiome composition. Our results demonstrate the power of this approach in the study of prehistoric humans and will enable future research to reach a more holistic understanding of the population dynamics and ecology.

Bioarchaeological and palaeogenomic portrait of two Pompeians that died during the eruption of Vesuvius in 79 AD.

The archaeological site of Pompeii is one of the 54 UNESCO World Heritage sites in Italy, thanks to its uniqueness: the town was completely destroyed and buried by a Vesuvius' eruption in 79 AD. In this work, we present a multidisciplinary approach with bioarchaeological and palaeogenomic analyses of two Pompeian human remains from the Casa del Fabbro. We have been able to characterize the genetic profile of the first Pompeian' genome, which has strong affinities with the surrounding central Italian population from the Roman Imperial Age. Our findings suggest that, despite the extensive connection between Rome and other Mediterranean populations, a noticeable degree of genetic homogeneity exists in the Italian peninsula at that time. Moreover, palaeopathological analyses identified the presence of spinal tuberculosis and we further investigated the presence of ancient DNA from Mycobacterium tuberculosis. In conclusion, our study demonstrates the power of a combined approach to investigate ancient humans and confirms the possibility to retrieve ancient DNA from Pompeii human remains. Our initial findings provide a foundation to promote an intensive and extensive paleogenetic analysis in order to reconstruct the genetic history of population from Pompeii, a unique archaeological site.

First Glimpse into the Genomic Characterization of People from the Imperial Roman Community of Casal Bertone (Rome, First-Third Centuries AD).

This paper aims to provide a first glimpse into the genomic characterization of individuals buried in Casal Bertone (Rome, first-third centuries AD) to gain preliminary insight into the genetic makeup of people who lived near a tannery workshop, fullonica. Therefore, we explored the genetic characteristics of individuals who were putatively recruited as fuller workers outside the Roman population. Moreover, we identified the microbial communities associated with humans to detect microbes associated with the unhealthy environment supposed for such a workshop. We examined five individuals from Casal Bertone for ancient DNA analysis through whole-genome sequencing via a shotgun approach. We conducted multiple investigations to unveil the genetic components featured in the samples studied and their associated microbial communities. We generated reliable whole-genome data for three samples surviving the quality controls. The individuals were descendants of people from North African and the Near East, two of the main foci for tannery and dyeing activity in the past. Our evaluation of the microbes associated with the skeletal samples showed microbes growing in soils with waste products used in the tannery process, indicating that people lived, died, and were buried around places where they worked. In that perspective, the results represent the first genomic characterization of fullers from the past. This analysis broadens our knowledge about the presence of multiple ancestries in Imperial Rome, marking a starting point for future data integration as part of interdisciplinary research on human mobility and the bio-cultural characteristics of people employed in dedicated workshops.

The evolutionary history of the polyQ tract in huntingtin sheds light on its functional pro-neural activities.

Huntington's disease is caused by a pathologically long (>35) CAG repeat located in the first exon of the Huntingtin gene (HTT). While pathologically expanded CAG repeats are the focus of extensive investigations, non-pathogenic CAG tracts in protein-coding genes are less well characterized. Here, we investigated the function and evolution of the physiological CAG tract in the HTT gene. We show that the poly-glutamine (polyQ) tract encoded by CAGs in the huntingtin protein (HTT) is under purifying selection and subjected to stronger selective pressures than CAG-encoded polyQ tracts in other proteins. For natural selection to operate, the polyQ must perform a function. By combining genome-edited mouse embryonic stem cells and cell assays, we show that small variations in HTT polyQ lengths significantly correlate with cells' neurogenic potential and with changes in the gene transcription network governing neuronal function. We conclude that during evolution natural selection promotes the conservation and purity of the CAG-encoded polyQ tract and that small increases in its physiological length influence neural functions of HTT. We propose that these changes in HTT polyQ length contribute to evolutionary fitness including potentially to the development of a more complex nervous system.

Ancient genomes from a rural site in Imperial Rome (1st-3rd cent. CE): a genetic junction in the Roman Empire.

BACKGROUND: Rome became the prosperous Capital of the Roman Empire through the political and military conquests of neighbouring areas. People were able to move Romeward modifying the Rome area's demographic structure. However, the genomic evidence for the population of one of the broadest Empires in antiquity has been sparse until recently. AIM: The genomic analysis of people buried in Quarto Cappello del Prete (QCP) necropolis was carried out to help elucidate the genomic structure of Imperial Rome inhabitants. SUBJECTS AND METHODS: We recruited twenty-five individuals from QCP for ancient DNA analysis through whole-genome sequencing. Multiple investigations were carried out to unveil the genetic components featuring in the studied samples and the community's putative demographic structure. RESULTS: We generated reliable whole-genome data for 7 samples surviving quality controls. The distribution of Imperial Romans from QCP partly overlaps with present-day Southern Mediterranean and Southern-Near Eastern populations. CONCLUSION: The genomic legacy with the south-eastern shores of the Mediterranean Sea and the Central and Western Northern-African coast funerary influence pave the way for considering people buried in QCP as resembling a Punic-derived human group.

Uniparental Lineages from the Oldest Indigenous Population of Ecuador: The Tsachilas.

Together with Cayapas, the Tsachilas constitute the oldest population in the country of Ecuador and, according to some historians, they are the last descendants of the ancient Yumbos. Several anthropological issues underlie the interest towards this peculiar population: the uncertainty of their origin, their belonging to the Barbacoan linguistic family, which is still at the center of an intense linguistic debate, and the relations of their Yumbo ancestors with the Inca invaders who occupied their ancient territory. Our contribution to the knowledge of their complex past was the reconstruction of their genetic maternal and paternal inheritance through the sequencing of 70 entire mitochondrial genomes and the characterization of the non-recombinant region of the Y chromosome in 26 males. For both markers, we built comprehensive datasets of various populations from the surrounding geographical area, northwestern South America, NW, with a known linguistic affiliation, and we could then compare our sample against the overall variability to infer relationships with other Barbacoan people and with other NW natives. We found contrasting patterns of genetic diversity for the two markers, but generally, our results indicated a possible common origin between the Tsachilas, the Chachi, and other Ecuadorian and Colombian Barbacoans and are suggestive of an interesting ancient linkage to the Inca invaders in Yumbo country.

How Does Diet Influence Our Lives? Evaluating the Relationship between Isotopic Signatures and Mortality Patterns in Italian Roman Imperial and Medieval Periods.

The present research investigates the relationship between dietary habits and mortality patterns in the Roman Imperial and Medieval periods. The reconstructions of population dynamics and subsistence strategies provide a fascinating source of information for understanding our history. This is particularly true given that the changes in social, economic, political, and religious aspects related to the transition from the Roman period to the Middle Ages have been widely discussed. We analyzed the isotopic and mortality patterns of 616 individuals from 18 archeological sites (the Medieval Latium sites of Colonna, Santa Severa, Allumiere, Cencelle, and 14 Medieval and Imperial funerary contexts from Rome) to compile a survivorship analysis. A semi-parametric approach was applied, suggesting variations in mortality patterns between sexes in the Roman period. Nitrogen isotopic signatures influenced mortality in both periods, showing a quadratic and a linear effect for Roman Imperial and Medieval populations, respectively. No influence of carbon isotopic signatures has been detected for Roman Imperial populations. Conversely, increased mortality risk for rising carbon isotopic values was observed in Medieval samples.

Exploring mobility in Italian Neolithic and Copper Age communities.

As a means for investigating human mobility during late the Neolithic to the Copper Age in central and southern Italy, this study presents a novel dataset of enamel oxygen and carbon isotope values (δ18Oca and δ13Cca) from the carbonate fraction of biogenic apatite for one hundred and twenty-six individual teeth coming from two Neolithic and eight Copper Age communities. The measured δ18Oca values suggest a significant role of local sources in the water inputs to the body water, whereas δ13Cca values indicate food resources, principally based on C3 plants. Both δ13Cca and δ18Oca ranges vary substantially when samples are broken down into local populations. Statistically defined thresholds, accounting for intra-site variability, allow the identification of only a few outliers in the eight Copper Age communities, suggesting that sedentary lifestyle rather than extensive mobility characterized the investigated populations. This seems to be also typical of the two studied Neolithic communities. Overall, this research shows that the investigated periods in peninsular Italy differed in mobility pattern from the following Bronze Age communities from more northern areas.

Leopoli-Cencelle (9th-15th centuries CE), a centre of Papal foundation: bioarchaeological analysis of the skeletal remains of its inhabitants.

BACKGROUND: The medieval city of Leopoli-Cencelle (9th-15th centuries CE) represents an exceptional study-model for extending our knowledge of the Italian Medieval period due not only to the large sample size available but also to the widespread presence of material data and a well preserved archaeological context. AIM: This research aims to reconstruct the osteobiography of the inhabitants of this centre of Papal foundation. SUBJECTS AND METHODS: The analysed sample counts 877 individuals. Scientifically established anthropological morphological methods were used for assessing their biological profile as well as for reconstructing lifestyle and health status. RESULTS: The sample consists of 62.49% adults and 37.51% non-adults. The mortality pattern shows the highest peak prior to 1 year and between 1 and 6 years of age and a reduced longevity of female individuals as commonly observed in pre-antibiotic era populations. Metric and musculoskeletal stress markers revealed different biomechanical stress between sexes probably carrying out different working activities. The palaeopathological analysis supports a general good health status with the exception of a few specific cases. CONCLUSIONS: The present research helps shed light on the lifestyle of the inhabitants of Leopoli-Cencelle, enhancing a better understanding of the Italian Middle Ages.

A multidisciplinary approach for investigating dietary and medicinal habits of the Medieval population of Santa Severa (7th-15th centuries, Rome, Italy).

A multidisciplinary approach, combining stable isotope analysis from bone proteins and investigations on dental calculus using DNA analysis, light microscopy, and gas chromatography coupled with mass spectrometry, was applied to reconstruct dietary and medicinal habits of the individuals recovered in the cemetery of the Castle of Santa Severa (7th-15th centuries CE; Rome, Italy). Stable isotope analysis was performed on 120 humans, 41 faunal specimens and 8 charred seeds. Dental calculus analyses were carried out on 94 samples. Overall, isotope data indicated an omnivorous diet based on C3-terrestrial protein, although some individuals possessed carbon values indicative of C4 plant consumption. In terms of animal protein, the diet was probably based on cattle, sheep, pig and chicken products, as witnessed by the archaeozoological findings. Evidence from calculus suggested the consumption of C3 cereals, Fabaceae, Fagaceae, milk and dairy products. Secondary metabolites of herbs and wine were also detected. The detection of marine fish ancient DNA, as well as of ω3 fatty acids in calculus, hypothesized the consumption of marine foodstuffs for this coastal population, despite the lack of a clear marine isotopic signal and the presence of polyunsaturated fatty acids in plant tissues. Moreover, the knowledge of ethnopharmacological tradition and the application of medicinal plants (e.g. Punica granatum L., Ephedra sp. L.) were also identified. The detection of artemisinin, known to have antimalarial properties, led to hypothesize the presence of malaria in the area. Altogether, the combined application of microscopy and biomolecular techniques provided an innovative reconstruction of Medieval lifeways in Central Italy.

Concerted variation of the 3' regulatory region of Ig heavy chain and Gm haplotypes across human continental populations.

OBJECTIVES: The 3' regulatory region of the immunoglobulin heavy chain gene (IGH) includes the HS1.2 enhancer displaying length polymorphism with four known variants. The goal of the research was to provide an overview of this variability and of its evolutionary significance across human populations. MATERIALS AND METHODS: We compiled published and original data on HS1.2 polymorphism in 3,100 subjects from 26 human populations. Moreover, we imputed the haplotypic arrangement of the HS1.2 region in the 1000 Genomes Project (1KGP). In this dataset, imputation could also be obtained for the G1m-G3m allotype by virtue of the precise correspondence between serological types and amino acid (and DNA) substitutions in IGHG1 and IGHG3. RESULTS: HS1.2 variant frequencies displayed similar patterns of continental partitioning as those reported in the literature for the physically neighboring IGHG1-IGHG3 system. The 1KGP data revealed that linkage disequilibrium (LD) can explain the spread of joint HS1.2-IGHG1-IGHG3 associations across continents and within continental populations, with stronger LD out of Africa and the features of an evolutionarily stable genomic block with differential expression in lymphoblastoid cell lines. DISCUSSION: Strong population structuring involves at least the entire 70 kb genomic region here considered, due to the tight LD which maintained HS1.2, IGHG1, and IGHG3 in nonrandom arrangements. This might be key to better understand the evolutionary path of the entire genomic region driven by immune response capabilities, during the formation of continental gene pools.

Dissecting the Pre-Columbian Genomic Ancestry of Native Americans along the Andes-Amazonia Divide.

Extensive European and African admixture coupled with loss of Amerindian lineages makes the reconstruction of pre-Columbian history of Native Americans based on present-day genomes extremely challenging. Still open questions remain about the dispersals that occurred throughout the continent after the initial peopling from the Beringia, especially concerning the number and dynamics of diffusions into South America. Indeed, if environmental and historical factors contributed to shape distinct gene pools in the Andes and Amazonia, the origins of this East-West genetic structure and the extension of further interactions between populations residing along this divide are still not well understood. To this end, we generated new high-resolution genome-wide data for 229 individuals representative of one Central and ten South Amerindian ethnic groups from Mexico, Peru, Bolivia, and Argentina. Low levels of European and African admixture in the sampled individuals allowed the application of fine-scale haplotype-based methods and demographic modeling approaches. These analyses revealed highly specific Native American genetic ancestries and great intragroup homogeneity, along with limited traces of gene flow mainly from the Andes into Peruvian Amazonians. Substantial amount of genetic drift differentially experienced by the considered populations underlined distinct patterns of recent inbreeding or prolonged isolation. Overall, our results support the hypothesis that all non-Andean South Americans are compatible with descending from a common lineage, while we found low support for common Mesoamerican ancestors of both Andeans and other South American groups. These findings suggest extensive back-migrations into Central America from non-Andean sources or conceal distinct peopling events into the Southern Continent.

Mitochondrial characterisation of two Spanish populations from the Vera and Bejar valleys (Central Spain).

This survey reports the mitochondrial data of two Spanish populations living in the Vera and Bejar valleys, on the opposite slopes of the Sierra de Gredos (Central Spain), which crosses Spain east to west. The aim of the study was to characterise the mitochondrial genetic pool of the Vera and Bejar populations to investigate a putative mitogenetic differentiation between them, evidence that would support the role of the Sierra de Gredos as a genetic barrier in their micro-evolutionary histories. Blood samples of 137 people (66 from Vera and 71 from Bejar) were collected and mtDNA hypervariable regions I and II (HVR-I and HVR-II) were dissected along with several mtDNA-coding region SNPs. The main European mitochondrial lineages have been found both in Vera and in Bejar, together with the typical African haplogroups L (in Vera) and U6 (in Bejar). FST value and the 95% credible regions calculated for haplogroup frequencies do not reveal genetic differentiation among the populations. Vera and Bejar contain an expected mitochondrial variability within them, but they do not seem to be genetically different from each other, leading us to conclude that the Sierra de Gredos is not a significant genetic barrier in their maternal genetic history.

Who were the miners of Allumiere? A multidisciplinary approach to reconstruct the osteobiography of an Italian worker community.

This research presents an in-depth study of the skeletal remains collected from the archaeological site of Allumiere (15th-16th centuries CE; Rome, Italy). A multidisciplinary approach was used, combining skeletal biology, molecular anthropology and archaeobotany with the aim of reconstructing the osteobiography of the alum miners buried at the site. Since 1460, the area of the Tolfa Mountains was significant for the exploitation of alum which was used for a wide range of purposes in the Middle Ages, ranging from woven production to medical practice. A total of 70 individuals (63 adults and 7 juveniles) were studied. The sex ratio of the community indicated a higher prevalence of males with respect to females. Morphological examination indicated occupational musculoskeletal stress markers, which might reflect the specific phase of alum production that each individual was occupied in. Dietary reconstruction was primarily performed through carbon and nitrogen stable isotope analysis with integration of the results obtained by microscopic, genetic and GC-MS investigations on dental calculus. The diet was omnivorous, indicating a reliance on C3-terrestrial protein and evidence for limited C4 consumption by some individuals. Herbivores, such as sheep and cattle, appear to have contributed to the diet more than pigs and chickens. Consumption of Fagaceae and Poaceae species was predominant; moreover, indicators of Brassicaceae and milk and its derivatives were abundantly recurrent in the population, followed by plant oils and theophylline. Furthermore, the detection of pharmacological alkaloids indicated the knowledge and application of medicinal plants by the community. The novel use of multiple techniques based on cutting-edge technologies has provided a unique window on the lifestyles of individuals from one of the first Italian settlements of alum workers.

Signs of continental ancestry in urban populations of Peru through autosomal STR loci and mitochondrial DNA typing.

The human genetic diversity around the world was studied through several high variable genetic markers. In South America the demic consequences of admixture events between Native people, European colonists and African slaves have been displayed by uniparental markers variability. The mitochondrial DNA (mtDNA) has been the most widely used genetic marker for studying American mixed populations, although nuclear markers, such as microsatellite loci (STRs) commonly used in forensic science, showed to be genetically and geographically structured. In this work, we analyzed DNA from buccal swab samples of 296 individuals across Peru: 156 Native Amazons (Ashaninka, Cashibo and Shipibo from Ucayali, Huambiza from Loreto and Moche from Lambayeque) and 140 urban Peruvians from Lima and other 33 urban areas. The aim was to evaluate, through STRs and mtDNA variability, recent migrations in urban Peruvian populations and to gain more information about their continental ancestry. STR data highlighted that most individuals (67%) of the urban Peruvian sample have a strong similarity to the Amazon Native population, whereas 22% have similarity to African populations and only ~1% to European populations. Also the maternally-transmitted mtDNA confirmed the strong Native contribution (~90% of Native American haplogroups) and the lower frequencies of African (~6%) and European (~3%) haplogroups. This study provides a detailed description of the urban Peruvian genetic structure and proposes forensic STRs as a useful tool for studying recent migrations, especially when coupled with mtDNA.

Mitochondrial variability in the Mediterranean area: a complex stage for human migrations.

CONTEXT: The Mediterranean area has always played a significant role in human dispersal due to the large number of migratory events contributing to shape the cultural features and the genetic pool of its populations. OBJECTIVE: This paper aims to review and diachronically describe the mitogenome variability in the Mediterranean population and the main demic diffusions that occurred in this area over time. METHODS: Frequency distributions of the leading mitochondrial haplogroups have been geographically and chronologically evaluated. The variability of U5b and K lineages has been focussed to broaden the knowledge of their genetic histories. RESULTS: The mitochondrial genetic makeup of Palaeolithic hunter-gatherers is poorly defined within the extant Mediterranean populations, since only a few traces of their genetic contribution are still detectable. The Neolithic lineages are more represented, suggesting that the Neolithic revolution had a marked effect on the peopling of the Mediterranean area. The largest effect, however, was provided by historical migrations. CONCLUSION: Although the mitogenome variability has been widely used to try and clarify the evolution of the Mediterranean genetic makeup throughout almost 50 000 years, it is necessary to collect whole genome data on both extinct and extant populations from this area to fully reconstruct and interpret the impact of multiple migratory waves and their cultural and genetic consequences on the structure of the Mediterranean populations.