Genome diversity in the Neolithic Globular Amphorae culture and the spread of Indo-European languages

It is unclear whether Indo-European languages in Europe spread from the Pontic steppes in the late Neolithic, or from Anatolia in the Early Neolithic. Under the former hypothesis, people of the Globular Amphorae culture (GAC) would be descended from Eastern ancestors, likely representing the Yamnaya culture. However, nuclear (six individuals typed for 597 573 SNPs) and mitochondrial (11 complete sequences) DNA from the GAC appear closer to those of earlier Neolithic groups than to the DNA of all other populations related to the Pontic steppe migration. Explicit comparisons of alternative demographic models via approximate Bayesian computation confirmed this pattern. These results are not in contrast to Late Neolithic gene flow from the Pontic steppes into Central Europe. However, they add nuance to this model, showing that the eastern affinities of the GAC in the archaeological record reflect cultural influences from other groups from the East, rather than the movement of people

Patterns of genetic and linguistic variation. A study of uniparental markers.

This dissertation is divided in three sections and focuses on two of the projects I worked on during my three-years PhD, funded by a European Research Council (ERC) grant LanGeLin. Both the projects share the uniparental markers as tool used for the investigation of the human evolutionary history, but each of them addresses different scientific questions by means of a different combination of molecular and statistical methods. Part I is a technical summary on current knowledge about uniparental markers features and on the pros and cons of their usage for addressing questions stemming from the fields of linguistics and archaeology. Part II summarizes the results of one of the ERC-founded LanGeLin works; here I describe the comparison of patterns of genetic and liguistic diversity in 36 Eurasian populations. The ERC-founded LanGeLin project aims to improve our understanding about the coevolution of language and genes. R. Sokal and L.L. Cavalli-Sforza in 1988 showed that a correlation between genetic and linguistic variation within major language families is actually present, but due to imperfect methods to quantify linguistic variation, it has been difficult to compare populations belonging to distant linguistic groups. Thanks to the newly PCM linguistic method, a new way to compare languages is now available, based on stable linguistic syntax features. It is now possible to test the correlation between genetic and linguistic data in a broad geo-linguistic scale, as this thesis will do, and to interpret in evolutionary terms both the rule and the exceptions. It is also possible to study maternal and paternal lineages separately, to inquire their migrational histories. Two different migrational histories emerged, with women dispersing at a higher rate than men. When comparing genetic and linguistic features a neither obvious nor simple pattern is detectable: correlations between languages and DNA variants depend on the geographical area and the genetic markers considered. Part III addresses questions related with the analysis of complete mitochondrial sequences from Mesolithic (Ms) times, which allowed us to address questions regarding Neolithic (Ne) and pre-Neolithic (pN) peopling of Sardinia. We investigated the role of two Ms Sardinian mtDNA sequences in the European context. Little is known about the genetic prehistory of Sardinia because of the scarcity of pN human remains. Modern Sardinians are known as genetic outliers in Europe, showing unusually high levels of internal diversity and a close relationship to early European Ne farmers. However, how far this peculiar genetic structure extends and how it originated was to date impossible to test. Here I present the first and oldest complete mtDNA sequences from Sardinia, dated back to 10,000 yBP. These two individuals belong to rare mtDNA lineages never been found before in Ms samples and that are currently present at low frequencies also in the whole Europe. When compared with other European pN data, the Ms Sardinian sequences appeared already well differentiated, and in general more similar to pre-Last Glacial Maximum populations, than to coeval sequences. As a side project, I was also involved in the study of the differences in twinning rate (tr) among human populations of Africa (where the tr is maximum), Europe and Asia (where the tr is minimum). The contact point between these projects was represented by the common bioinformatics and biostatistical tools needed for analysis of large genomic. Although I considered that, for the sake of consistency, this thesis will mostly focus on the ERC-funded project, I am enclosing, in the final Manuscripts section, both papers produced during my doctoral years.Questa tesi riassume l’attività di ricerca da me svolta durante i tre anni di dottorato, sovvenzionato dal progetto ERC LanGeLin, il cui scopo principale è di migliorare le conoscenze sulla co-evoluzione di lingue e geni. I progetti descritti condividono l’uso di marcatori uniparentali usati per gli studi di evoluzione umana, ma differiscono per la combinazione di metodi molecolari e statistici. La Parte I descrive lo stato dell’arte dei marcatori uniparentali e i pro e contro del loro utilizzo in ambito linguistico e archeologico. La Parte II riassume i risultati delle ricerche condotte nell’ambito del progetto LanGeLin che descrive la diversità dei pattern genetici e linguistici in 36 popolazioni Euroasiatiche. Il progetto LanGeLin (Language and Gene Lineages), finanziato dal “European Research Council” ha lo scopo di testare l’ipotesi di Darwin presentata in “Origine delle specie”. Darwin intuì che l’albero filogenetico delle diverse sottospecie umane, potesse sovrapporsi a quello ottenuto a partire dalle diverse lingue, offrendo di fatto la possibilità di studiare la genealogia delle lingue e allo stesso tempo capire come le differenze tra queste avrebbero permesso di far luce sugli aspetti elusivi della storia demografica umana. R. Sokal e L.L. Cavalli-Sforza nel 1988 hanno elucidato come la comparazione dei vocaboli rifletta la correlazione fra variabilità genetica e linguistica nelle maggiori famiglie linguistiche ma, a causa di metodi linguistici, risulta difficile comparare popolazioni derivanti da gruppi linguistici distanti. Il nuovo metodo linguistico PCM si basa sulle caratteristiche linguistiche più stabili della sintassi. È stato dunque possibile, anche in questa tesi, testare su larga scala geo-linguistica la correlazione tra dati genetici e linguistici. Lo studio delle discendenze materne e paterne è stato condotto separatamente per indagarne le relative storie di migrazione: due differenti storie sono emerse dall’analisi del Ychr (discendenza patrilineare) e del mtDNA (discendenza matrilineare). Non ovvie considerazioni sono scaturite dalla comparazione delle caratteristiche genetiche e linguistiche, che ha portato a definire come la correlazione tra lingue e sequenza genetica sia dipendente dall’area geografica e dai marcatori genetici considerati. La Parte III descrive l’analisi di sequenze di mtDNA del Mesolitico (Ms) che ci ha permesso di indagare sul popolamento della Sardegna in periodo Neolitico (Ne) e pre-Neolitico (pN). Lo studio è stato incentrato su due sequenze mitocondriali sarde Ms in relazione al contesto europeo. C’è ancora molta incertezza sulla variabilità genetica della Sardegna preistorica, a causa della scarsità di resti umani Ne. Dal punto di vista genetico, i sardi moderni possono considerarsi un gruppo a se stante rispetto al resto dell’Europa continentale, mostrando alti livelli di diversità interna e una forte vicinanza con i primi coltivatori europei del Ne. Questa tesi riporta le due prime sequenze mtDNA complete sarde, datate circa 10000 anni fa. I due individui confermano un’occupazione mesolitica dell’isola e rappresentano un aplotipo mai trovato prima in Sardegna mesolitica e con basse frequenze nell’intera Europa. Le due sequenze risultano ben differenziate se comparate con altri dati europei pN, e più simili a popolazioni dell’era pre-glaciale che a popolazioni coeve. Analisi di inferenza Bayesiana hanno mostrato come i primi abitanti dell’isola abbiano contribuito poco al popolamento attuale dell’isola, la cui diversità genetica deriva da migrazioni dal continente in tempi neolitici. Un progetto portato avanti parallelamente, ha riguardato lo studio di frequenze alleliche in gemelli dizigotici provenienti da popolazioni umane africane, europee ed asiatiche. Le tecniche bioinformatiche e biostatistiche usate per le analisi genomiche su larga scala, fanno da collante con i precedenti progetti descritti

Natural selection accounts for differences in dizygotic twinning rates at the worldwide scale

22pop_random0.1sorted_neutral.map - plink map file for Bayenv; reference dataset<br><div>22pop_random0.1sorted_neutral.ped - plink ped file for Bayenv; reference dataset<br></div><div>22pop_random0.1sorted_neutral_bayenv - Input file for Bayenv; reference dataset<br></div><div><div>22pop_continental_maf0.005_83genes.map - plink map file for Bayenv; candidate dataset<br></div><div>22pop_continental_maf0.005_83genes.ped - plink ped file for Bayenv; candidate dataset<br></div><div>22pop_continental_maf0.005_83genes_bayenv - Input file for Bayenv; candidate dataset</div></div><div>random0.1sorted_neutral.map - plink map file for BayeScan; reference dataset<br></div><div>random0.1sorted_neutral.ped - plink ped file for BayeScan; reference dataset<br></div><div>random0.1sorted_neutral_bayescan - Input file for Bayescan; reference dataset </div><div>continental_maf0.005_83genes.map - plink map file for BayeScan; candidate dataset<br></div><div>continental_maf0.005_83genes.ped - plink ped file for BayeScan; candidate dataset<br></div><div>continental_maf0.005_83genes_bayescan - Input file for Bayescan; candidate dataset <br></div><div>twins_rate_22pop_Oct2016 - Values of the environmental variable (twins rate) used as input for Bayenv<br></div

Electronic Supplementary Information from Genome diversity in the Neolithic Globular Amphorae culture and the spread of Indo-European languages

Supplementary Materials, 16 supplementary tables and appendi

Low dose aspirin and clinical outcomes in patients with SARS-CoV-2 pneumonia: a propensity score-matched cohort analysis from the National SIMI‑COVID‑19 Registry

Background: SARS- CoV-2 virus has had dramatic consequences worldwide being able to cause acute respiratory distress syndrome (ARDS), massive thrombosis and pulmonary embolism and, finally, patients' death. In COVID-19 infection, platelets have a procoagulant phenotype that can cause thrombosis in the pulmonary and systemic vascular network. Aspirin is a well-known anti-platelet drug widely used for the prevention of cardiovascular events and systematic reviews suggest a possible benefit of low-dose aspirin (LDA) use in the prevention and treatment of ARDS in patients with COVID-19 infection. However, several studies are available in the literature which do not support any benefits and no association with the patients' outcome. Therefore, currently available data are inconclusive. Materials and patients: Data from the nationwide cohort multicenter study of the Italian Society of Internal Medicine (SIMI) were analyzed. We conducted a propensity score-matched cohort analysis to investigate the impact of chronic assumption of LDA on mortality of adult COVID-19 patients admitted in Internal Medicine Units (IMU). Data from 3044 COVID-19 patients who referred to 41 Italian hospitals between February 3rd to May 8th 2020 were analyzed. A propensity score-matched analysis was conducted using the following variables: age, sex, hypertension, hyperlipidemia diabetes, atrial fibrillation, cerebrovascular disease, COPD, CKD and stratified upon LDA usage, excluding anticoagulant treatment. After matching, 380 patients were included in the final analysis (190 in LDA group and 190 in no-LDA group). Results: 66.2% were male, median age was 77 [70-83]. 34.8% of the population died during the hospitalization. Cardiovascular diseases were not significantly different between the groups. After comparison of LDA and no-LDA subgroups, we didn't record a significant difference in mortality rate (35.7% vs 33.7%) duration of hospital stay and ICU admission. In a logistic regression model, age (OR 1.05; 95% CI 1.01-1.09), FiO2 (OR 1.024; 95% CI 1.03-1.04) and days between symptoms onset and hospitalization (OR 0.93; 95% CI 0.87-0.99) were the only variables independently associated with death

A genetic perspective on Longobard-Era migrations

From the first century AD, Europe has been interested by population movements, commonly known as Barbarian migrations. Among these processes, the one involving the Longobard culture interested a vast region, but its dynamics and demographic impact remains largely unknown. Here we report 87 new complete mitochondrial sequences coming from nine early-medieval cemeteries located along the area interested by the Longobard migration (Czech Republic, Hungary and Italy). From the same areas, we sampled necropoleis characterized by cultural markers associated with the Longobard culture (LC) and coeval burials where no such markers were found, or with a chronology slightly preceding the presumed arrival of the Longobards in that region (NLC). Population genetics analysis and demographic modeling highlighted a similarity between LC individuals, as reflected by the sharing of quite rare haplogroups and by the degree of genetic resemblance between Hungarian and Italian LC necropoleis estimated via a Bayesian approach, ABC. The demographic model receiving the strongest statistical support also postulates a contact between LC and NLC communities, thus indicating a complex dynamics of admixture in medieval Europe