Search

N/A

Summary - The animal and plant biodiversity of the Italian territory is known to be one of the richest in the Mediterranean basin and Europe as a whole, but does the genetic diversity of extant human populations show a comparable pattern? According to a number of studies, the genetic structure of Italian populations retains the signatures of complex peopling processes which took place from the Paleolithic to modern era. Although the observed patterns highlight a remarkable degree of genetic heterogeneity, they do not, however, take into account an important source of variation. In fact, Italy is home to numerous ethnolinguistic minorities which have yet to be studied systematically. Due to their difference in geographical origin and demographic history, such groups not only signal the cultural and social diversity of our country, but they are also potential contributors to its bio-anthropological heterogeneity. To fill this gap, research groups from four Italian Universities (Bologna, Cagliari, Pisa and Roma Sapienza) started a collaborative study in 2007, which was funded by the Italian Ministry of Education, University and Research and received partial support by the Istituto Italiano di Antropologia. In this paper, we present an account of the results obtained in the course of this initiative. Four case-studies relative to linguistic minorities from the Eastern Alps, Sardinia, Apennines and Southern Italy are first described and discussed, focusing on their micro-evolutionary and anthropological implications. Thereafter, we present the results of a systematic analysis of the relations between linguistic, geographic and genetic isolation. Integrating the data obtained in the course of the long-term study with literature and unpublished results on Italian populations, we show that a combination of linguistic and geographic factors is probably responsible for the presence of the most robust signatures of genetic isolation. Finally, we evaluate the magnitude of the diversity of Italian populations in the European context. The human genetic diversity of our country was found to be greater than observed throughout the continent at short (0-200 km) and intermediate (700-800km) distances, and accounted for most of the highest values of genetic distances observed at all geographic ranges. Interestingly, an important contribution to this pattern comes from the “linguistic islands” (e.g. German speaking groups of Sappada and Luserna from the Eastern Italian Alps), further proof of the importance of considering social and cultural factors when studying human genetic variation.

In this paper, we present a study of genetic variation in sub-Saharan Africa, which is based on published and unpublished data on fast-evolving (hypervariable region 1 of mitochondrial DNA and six microsatellites of Y chromosome) and slow-evolving (haplogroup frequencies) polymorphisms of mtDNA and Y chromosome. Our study reveals a striking difference in the genetic structure of food-producer (Bantu and Sudanic speakers) and hunter-gatherer populations (Pygmies, Kung, and Hadza). In fact, the ratio of mtDNA to Y-chromosome Nupsilon is substantially higher in food producers than in hunter-gatherers as determined by fast-evolving polymorphisms (1.76 versus 0.11). This finding indicates that the two population groups differ substantially in female and male migration rate and/or effective size. The difference also persists when linguistically homogeneous populations are used and outlier populations are eliminated (1.78 vs 0.19) or when the jacknife procedure is applied to a paired population data set (1.32 to 7.84 versus 0.14 to 0.66). The higher ratio of mtDNA to Y-chromosome Nnu in food producers than in hunter-gatherers is further confirmed by the use of slow-evolving polymorphisms (1.59 to 7.91 versus 0.12 to 0.35). To explain these results, we propose a model that integrates demographic and genetic aspects and incorporates ethnographic knowledge. In such a model, the asymmetric gene flow, polyginy, and patrilocality play an important role in differentiating the genetic structure of sub-Saharan populations. The existence of an asymmetric gene flow is supported by the phylogeographic features of mtDNA and Y-chromosome haplogroups found in the two population groups. The role of polyginy and patrilocality is sustained by the evidence of a differential pressure of genetic drift and gene flow on maternal and paternal lineages of food producers and hunter-gatherers that is revealed through the analysis of mitochondrial and Y-chromosomal intrapopulational variation.

Among the several factors affecting the genetic makeup of human populations, language represents a crucial component, potentially acting as a genetic barrier separating different ethnic groups. The Albanian-speaking Arbërëshe are one of the largest linguistic minorities in Italy, whose origin is generally connected with population movements of Albanians occurred between the 15th and the 16th centuries, mainly linked to the invasion of Balkans by the Ottoman Empire. Actually, the presence of these populations in Italy is the complex result of several migration waves (at least eight), whether coming directly from Albania or arrived in Italy after intermediate steps in Greece (Peloponnese). Originating from a restricted number of founders and having preserved their isolation from the surrounding populations, Arbërëshe groups are characterized by high levels of within village endogamy and inbreeding, and marked differentiation among different villages. Furthermore, despite many scholars generally agree that Arbërisht (language spoken by Arbërëshe) belongs to the Tosk dialect group, the Albanian spoken in Italy is actually not completely homogeneous among all Arbërëshe communities. History, identity and culture of each Arbërëshe group are therefore the distinct product of different origin and migration processes, as well as of different degrees of isolation or interaction with surrounding populations, over five centuries of independent evolution. In this context, we used a micro-geographic approach aimed at comparing different linguistic isolates with their geographic neighbors and putative source populations, to facilitate the reconstruction of historical and micro-evolutionary processes shaping current population genetic structure, particularly focusing on the role of culture vs. geography. For this purpose more than 500 samples from Arbërëshe of Sicily and Calabria, together as samples from both Sicily/South-Italy and the Balkans, have been analyzed for Y-chromosome diversity by using 32 SNPs and 17 STRs. The comparison with Italian and Balkan genetic landscapes will allow to 1) describe the genetic structure of Arbërëshe communities and evaluate the degree of isolation or admixture of each group, 2) investigate the genetic ancestry of each isolate by assessing the genetic connection with putative source populations. Preliminary results reveal high levels of within-population genetic variability and a marked genetic differentiation between the two Arbërëshe group. Accordingly, comparison with Italian and Balkan populations suggests distinct origins and different degrees of admixture. Ongoing analysis on this dataset, together with the maternal perspective, will help to shed light on factors affecting the gene-culture co-evolution processes in these model-populations.

Due to their low genetic complexity and relative environmental and socio-cultural uniformity, geographical and/or cultural isolates provide an unique opportunity to reconstruct processes shaping human biodiversity. Groups with remarkable historic and linguistic peculiarities, often living in a mountainous setting, are widely dispersed in the Italian territory from the Alps to the main islands. Following and developing previous work by the same research network, the project initiative “Human biodiversity in Italy: micro-evolutionary patterns” is aimed at achieving an extensive genetic characterization of these populations and studying the relations between patterns of genetic diversity and cultural, historical and demographic factors. To this purpose, research units from the Universities of Bologna, Cagliari, Pisa and Roma Sapienza are collaborating in a multidisciplinary framework. The innovative aspects of this project are represented by: i) an accurate sampling strategy based on the history and the demographic structure of the populations; ii) a complete genotyping of uniparental and autosomal markers; iii) a participative involvement of the interested communities.

We briefly review the current status of anthropological and genetic studies of isolated populations and of their micro-evolutionary and biomedical applications, with particular emphasis on European populations. Thereafter, we describe the ongoing collaborative research project "Isolating the Isolates: geographic and cultural factors of human genetic variation" regarding Italian extant geographical and/or linguistic isolates, aimed at overcoming the limitations of previous studies regarding geographical coverage of isolates, number and type of genetic polymorphisms under study and suitability of the experimental design to investigate gene-culture coevolutionary processes. An interdisciplinary sampling approach will make it possible to collect several linguistic isolates and their geographic neighbours from Trentino, Veneto, Friuli, Tuscany, Sardinia and Calabria. This will be coupled with a shared genotyping strategy based on mitochondrial and Y-chromosomal polymorphisms. The results will be analyzed with a focus on the role of geographical and cultural factors in shaping human biodiversity. The aims of the project go beyond the simple reconstruction of the genetic structure and history of the examined groups. In fact, the study will also include an assessment for future bio-medical studies and the development of genetic and bio-demographic databases. Ethical and educational aspects are also foreseen by the project, by using informed consents together with disseminating activities in loco, completed by the creation of a dedicated web site for both scientific and public audiences.

The search for a method that utilizes biological information to predict humans’ place of origin has occupied scientists for millennia. Over the past four decades, scientists have employed genetic data in an effort to achieve this goal but with limited success. While biogeographical algorithms using next-generation sequencing data have achieved an accuracy of 700 km in Europe, they were inaccurate elsewhere. Here we describe the Geographic Population Structure (GPS) algorithm and demonstrate its accuracy with three data sets using 40,000–130,000 SNPs. GPS placed 83% of worldwide individuals in their country of origin. Applied to over 200 Sardinians villagers, GPS placed a quarter of them in their villages and most of the rest within 50 km of their villages. GPS’s accuracy and power to infer the biogeography of worldwide individuals down to their country or, in some cases, village, of origin, underscores the promise of admixture-based methods for biogeography and has ramifications for genetic ancestry testing., Current methods to identify the geographical origin of humans based on DNA data present limited accuracy. Here, the authors develop a new algorithm, the Genographic Population Structure (GPS), and demonstrate its ability to place worldwide individuals within their country or, in some cases, village of origin.

The Genographic Project is an international effort using genetic data to chart human migratory history. The project is non-profit and non-medical, and through its Legacy Fund supports locally led efforts to preserve indigenous and traditional cultures. In its second phase, the project is focusing on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide SNP genotyping, they were designed for medical genetic studies and contain medically related markers that are not appropriate for global population genetic studies. GenoChip, the Genographic Project's new genotyping array, was designed to resolve these issues and enable higher-resolution research into outstanding questions in genetic anthropology. We developed novel methods to identify AIMs and genomic regions that may be enriched with alleles shared with ancestral hominins. Overall, we collected and ascertained AIMs from over 450 populations. Containing an unprecedented number of Y-chromosomal and mtDNA SNPs and over 130,000 SNPs from the autosomes and X-chromosome, the chip was carefully vetted to avoid inclusion of medically relevant markers. The GenoChip results were successfully validated. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays for three continental populations. While all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. The GenoChip is a dedicated genotyping platform for genetic anthropology and promises to be the most powerful tool available for assessing population structure and migration history., Comment: 11 pages, 5 Figures, 2 supplementary notes

In order to attain a finer reconstruction of the peopling of southern and central-eastem Europe from the Levant, we determined the frequencies of eight lineages internal to the Y chromosomal haplogroup J, defined by biallelic markers, in 22 population samples obtained with a fine-grained sampling scheme. Our results partially resolve a major multifurcation of lineages within the haplogroup. Analyses of molecular variance show that the area covered by haplogroup J dispersal is characterized by a significant degree of molecular radiation for unique event polymorphisms within the haplogroup, with a higher incidence of the most derived sub-haplogroups on the northern Mediterranean coast, from Turkey westward; here, J diversity is not simply a subset of that present in the area in which this haplogroup, first originated. Dating estimates, based on simple tandem repeat loci (STR) diversity within each lineage, confirmed the presence of a major population structuring at the time of spread of haplogroup J in Europe and a punctuation in the peopling of this continent in the post-Neolithic, compatible with the expansion of the Greek world. We also present here, for the first time, a novel method for comparative dating of lineages, free of assumptions of STR mutation rates.

The genetic structure and interrelationships of six populations of the Garfagnana valley (Tuscany, Italy) were examined using chromosomal heteromorphisms concurrently with blood group system, red cell isozyme, and serum protein polymorphisms, secretor status, and surname frequency data. We aimed to evaluate the relationship of cytogenetic polymorphisms to more classical sources of gene frequency data in a population with a well-known demographic scenario. The R matrix technique (Harpending and Jenkins 1973) was used to estimate kinship coefficients, and the Harpending-Ward model (1982) and its extensions for quantitative traits (Relethford and Blangero 1990) were used to detect differential systematic pressure among population subdivisions. Mantel statistics were used to assess the significance of the correlations between cytogenetic, genetic, isonymy, geographic, and migration matrices. The analyses consistently gave similar results for the DA/DAPI cytogenetic heteromorphism and most gene frequency data. Both sets of results depend on migration patterns and on geographic distance among population subdivisions. However, C cytogenetic heteromorphism and some separately analyzed genetic markers did not fit the demogeographic pattern. Overall, it appears that data from different levels of the genetic hierarchy (namely, DNA regions encoding for classical biochemical markers and the noncoding highly variable cytogenetic bands of heterochromatin) can be treated and compared using the same analytical tools.

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.

The study of food choice, one of the most complex human traits, requires an integrated approach that takes into account environmental, socio-cultural and biological diversity. We recruited 183 volunteers from four geo-linguistic groups and highly diversified in terms of both genetic background and food habits from whom we collected genotypes and phenotypes tightly linked to taste perception. We confirmed previous genetic associations, in particular with stevioside perception, and noted significant differences in food consumption: in particular, broccoli, mustard and beer consumption scores were significantly higher (Adjusted P = 0.02, Adjusted P

A number of studies carried out since the early ‘70s has investigated the effects of isolation on genetic variation within and among human populations in diverse geographical contexts. However, no extensive analysis has been carried out on the heterogeneity among genomes within isolated populations. This issue is worth exploring since events of recent admixture and/or subdivision could potentially disrupt the genetic homogeneity which is to be expected when isolation is prolonged and constant over time. Here, we analyze literature data relative to 87,818 autosomal single-nucleotide polymorphisms, which were obtained from a total of 28 European populations. Our results challenge the traditional paradigm of population isolates as genetically (and genomically) uniform entities. In fact, focusing on the distribution of variance of intra-population diversity measures across individuals, we show that the inter-individual heterogeneity of isolated populations is at least comparable to the open ones. More in particular, three small and highly inbred isolates (Sappada, Sauris and Timau in Northeastern Italy) were found to be characterized by levels of this parameter largely exceeding that of all other populations, possibly due to relatively recent events of genetic introgression. Finally, we propose a way to monitor the effects of inter-individual heterogeneity in disease-gene association studies.