Group leaders: Prof. Antonio Torroni, Prof. Ornella Semino, Prof. Luca Ferretti, Prof. Anna Olivieri, Prof. Alessandro Achilli

Collaborators: Vincenza Battaglia, Marco Rosario Capodiferro (PhD student), Alessandro Raveane (Postdoc)

 One of the main objectives of the research group is the reconstruction, based on genetic and genomic data, of the evolutionary history and demographic events that have involved present and past human populations (at both micro and macro-geographic levels) and some animals (especially domestic animals and those living in close contact with our species). Genetic findings can be easily employed also in multidisciplinary studies involving apparently far away scientific and cultural contexts, from forensics to history, archaeology, linguistics, anthropology, education and public health.

The genetic systems under study are the autosomes as well as the uniparentally transmitted mitochondrial DNA (mtDNA) and male-specific portion of the Y chromosome (MSY). The latter two are not reshuffled by recombination and thus constitute a molecular archive of the history and migration of females and males, respectively, who transmitted them to subsequent generations. Our studies has also implications in biomedicine. For instance, the mitochondrial DNA contains 37 genes that are coding for components of respiratory chain enzyme complexes and are essential for cellular energy production. Thus, one of the aims of the research of this group is also to define the role of the “normal” sequence variation of mtDNA in some diseases (Parkinson’s, Alzheimer’s, diabetes, reduced fertility), in aging and athletic performance.

Research Topics:

1) Origin of populations from Europe and the Mediterranean area

The demographic and genetic history of Europe and surrounding regions is extremely complex. The purpose of this research is to investigate, through the analysis of modern and ancient DNA genomes, what aspects of the variability of European populations can be traced back to the first colonization of the continent by modern humans, to post – glacial expansions, the Neolithic diffusion and (or) more recent events of gene flow. Over the years our studies on this general topic have been very productive and have used as the main tool of investigation the two non-recombinant genetic systems (mtDNA and MSY), which we are now integrating with genome-wide analyses.

Collaborations: Prof. Fulvio Cruciani (Sapienza Univ. di Roma); Dr. Martin Bodner, Prof. Walther Parson (Innsbruck Medical Univ., Austria); Dr. Francesca Gandini, Prof. Maria Pala, Prof. Martin B. Richards (Univ. of Huddersfield, UK); Prof. Vincent Macaulay (Univ. of Glasgow, UK); Prof. Andrea Novelletto (Univ. Tor Vergata, Roma); Prof. Antonio Salas (Univ. of Santiago de Compostela, Spain); Prof. Richard Villems (Estonian Biocentre, Tartu, Estonia).

Recent publications:

• Phylogeography of human Y-chromosome haplogroup Q3-L275 from an academic/citizen science collaboration (2017)
• Origin and spread of human mitochondrial DNA haplogroup U7 (2017)
• Reconciling evidence from ancient and contemporary genomes: a major source for the European Neolithic within Mediterranean Europe (2017)
• Genomic insights into the origin of farming in the ancient Near East (2016)
• Mapping human dispersals into the Horn of Africa from Arabian Ice Age refugia using mitogenomes (2016)
• Phylogenetic applications of whole Y-chromosome sequences and the Near Eastern origin of Ashkenazi Levites (2013)

2) The genetic origin of Italian populations

Despite its small geographic area, the Italian peninsula, for geographical, climatic and historical reasons, has occupied for several millennia a central position in the flow of genetic exchange and commercial trades among ancient populations. The objective of this research line is to reconstruct the prehistorical and historical genetics of the early Italy at a very high level of genetic resolution in a very large number of subjects (covering all Italian regions). To accomplish this task, a genome-wide scan on rare and common SNPs as well as analyses of both uniparental genetic systems (MSY and mtDNA) are going to be performed.

Collaborations: Prof. Andrea Angius (Istituto di Ricerca Genetica e Biomedica – CNR, Cagliari); Prof. Cristian Capelli (Univ. of Oxford, UK); Prof. David Caramelli (Univ. di Firenze); Prof. Cristina Cattaneo (Univ. di Milano); Dr. Hovirag Lancioni, Dr. Irene Cardinali (Univ. di Perugia); Prof. Carlo Previderè (Dip. di Medicina Legale, Univ. di Pavia); Prof. Mait Metspalu (Estonian Biocentre, Tartu, Estonia).

Recent publications:

• Reconstructing the genetic history of Italians: new insights from a male (Y-chromosome) perspective (2018)
• Genealogical relationships between early medieval and modern inhabitants of Piedmont (2015)
• Small effective population size and genetic homogeneity in the Val Borbera isolate (2013)
• Mitochondrial DNA variation of modern Tuscans supports the near eastern origin of Etruscans (2007)

3) The peopling of Sardinia

Sardinian people are a “genetic outlier” in the European contest. Archaeological data point to a first evidence of modern human presence on the island dating back to about 13,000 years ago (Upper Palaeolithic). Distinctive genetic traits of Sardinians have been retrieved with all genetic systems, due to a combination of founder effects, geographic isolation, and selection. Recent paleo-genomic data based on nuclear genome markers have revealed that, among present-day populations, Sardinians retain the highest levels of genetic similarity with Early Neolithic farmers across Europe. However, this scenario appears in contrast with data provided by uniparentally-transmitted genetic systems. We are currently investigating on this topic, also from an ancient DNA perspective.

Collaborations: Prof. Andrea Angius, Prof. Francesco Cucca, Dr. Carlo Sidore (Istituto di Ricerca Genetica e Biomedica – CNR, Cagliari); Prof. Johannes Krause (Max Planck Institute for the Science of Human History, Germania).

Recent publications:

• Mitogenome Diversity in Sardinians: A Genetic Window onto an Island’s Past (2017)
• Mitochondrial haplogroup U5b3: a distant echo of the epipaleolithic in Italy and the legacy of the early Sardinians (2009)

 

4) The peopling of the Americas: a genetic perspective

The first peopling of the New World is a hot topic in genetics and anthropology. Archaeology, linguistics and genetics agree on the Asian origin of Native Americans. However, the arrival times of the first settlers, the number of migrations / expansions involved in the process and in the subsequent colonization of Central and South America, as well as the genetic consequences of the flourishing of the great Mesoamerican and Andean civilizations are still extensively debated. To clarify these issues, sequence analyses of the two non-recombinant genetic systems (MSY and mtDNA), both at the micro- and macro-geographic levels, are carried out in several modern populations and some ancient samples. In some contexts, these studies are integrated by genome-wide analyses at the nuclear level.

Collaborations: Dr. Martin Bodner, Prof. Walther Parson (Innsbruck Medical Univ., Austria); Prof. Richard Cooke (Smithsonian Tropical Research Institute, Panama); Prof. Ripan Malhi (Univ. of Illinois at Urbana-Champaign, US); Dr. Jorge A. Motta (Secretario Nacional de Ciencia y Tecnología e Innovación, Panama); Dr. Juan Miguel Pascale (Instituto Conmemorativo Gorgas de Estudios de la Salud, Panama); Dr. Ugo A. Perego (Genetic Genealogy Consultant, US).

Recent publications:

• Ancient human genomes-keys to understanding our past (2018)
• The peopling of South America and the trans-Andean gene flow of the first settlers (2018)
• The Paleo-Indian Entry into South America According to Mitogenomes (2018)
• Ancient individuals from the North American Northwest Coast reveal 10,000 years of regional genetic continuity (2017)
• The first peopling of South America: new evidence from Y-chromosome haplogroup Q (2013)
• Reconciling migration models to the Americas with the variation of North American native mitogenomes (2013)

5) A comparative analysis of historical-cultural and genetic data: conquest, commerce, crisis, culture and the Panamanian junction (1513-1671) (ERC CoG 648,535 – ArtEmpire)

The narrow Isthmus of Panama was a strategic node of the Spanish Empire and a crucial site for early modern globalization. This project combines analyses of historical documents with archaeological and archaeogenetic approaches to highlight the cultural and biological consequences of encounters between populations and goods from Europe, America, Africa and Asia in the Isthmus of Panama area during the sixteenth and seventeenth centuries.

Collaborations: Dr. Bethany Arhan (Universidad Pablo de Olavide, Spain); Dr. Corina Knipper (Curt-Engelhorn-Zentrum Archäometrie, Mannheim, Germany); Dr. Juan Martin, Dr. Javier Rivera (Universidad del Norte, Colombia).

Recent publications:

• Exploring the Y Chromosomal Ancestry of Modern Panamanians (2015)
• Decrypting the mitochondrial gene pool of modern Panamanians (2012)

 

6 ) Identification of new pathological mtDNA mutations and the roles of mitochondrial background (haplogroups) in the expression of diseases / phenotypes

The mitochondrial ATP production by the oxidative phosphorylation is essential for the maintenance of normal functions of organs and tissues. MtDNA mutations, by interfering with ATP synthesis, can cause serious maternally-transmitted diseases. The search for new disease-causing mtDNA mutations is carried out mainly on Leber’s Optic Neuropathy (LHON). In recent years, an important role of the “neutral” sequence variation of mtDNA has also been postulated for many complex diseases and other phenotypes (aging, athletic performance). To evaluate also these aspects, we are sequencing entire mitogenomes from numerous human populations and building up a database that includes representatives of each mtDNA haplogroup and sub-haplogroup present in our species.

Collaborations: Prof. Valerio Carelli (Univ. di Bologna); Dr. Cristina Cereda (IRCCS Istituto Neurologico Nazionale C. Mondino, Pavia); Prof. Alessandra Montecucco (Istituto di Genetica Molecolare – CNR, Pavia).

Recent publications:

• Haplogroup J mitogenomes are the most sensitive to the pesticide rotenone: Relevance for human diseases (2018)
• Peculiar combinations of individually non-pathogenic missense mitochondrial DNA variants cause low penetrance Leber’s hereditary optic neuropathy (2018)
• A missense MT-ND5 mutation in differentiated Parkinson Disease cytoplasmic hybrid induces ROS-dependent DNA Damage Response amplified by DROSHA (2017)
• Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions (2014)
• A novel in-frame 18-bp microdeletion in MT-CYB causes a multisystem disorder with prominent exercise intolerance (2014)
• Cybrid studies establish the causal link between the mtDNA m.3890G>A/MT-ND1 mutation and optic atrophy with bilateral brainstem lesions (2013)

 

7) The genetics of taste

The ability to perceive flavors is genetically determined and the perception of flavors is the main factor driving the choice of foods, causing their acceptance or rejection. On the other hand, the choice of foods is an important factor that can modulate the risk of common diseases, such as obesity, diabetes, metabolic syndrome, but also cardiovascular diseases and cancer. The aim of our work is to correlate the variations of genes involved in taste perception, and thus in food choices, with diet and health state, in particular with tumors of the digestive system.

Collaborations: Prof. G. Nadia Ranzani (Dip. di Biologia e Biotecnologie, Univ. di Pavia).

 

8) Origin and spread of the Asian tiger mosquito (Aedes albopictus)

Over the last 40 years, the tiger mosquito Aedes albopictus, indigenous to East Asia, has colonized every continent except Antarctica. Its spread has become a growing public health concern, being a competent vector for many arboviruses including those causing West Nile fever, yellow fever, Dengue fever, Saint Louis encephalitis and the recently emerged Zika fever.

The present study involves the definition and analysis of mitogenome sequence variation in samples from numerous African, European and American populations, in order to identify the ancestral Asian source(s) of Ae. albopictus adventive populations and their possible selective advantages as well as migration routes and expansion times.

Recent publications:

• The Worldwide Spread of the Tiger Mosquito as Revealed by Mitogenome Haplogroup Diversity (2016)

Collaborations: Dr. Paolo Gabrieli, Prof. Giuliano Gasperi, Prof. Ludvik Gomulski, Prof. Anna Malacrida (Department of Biology and Biotechnology, Univ. of Pavia).

 

9) Modes and times of domestication of some mammal species (Bos taurus, Bubalus bubalis, Ovis aeries, Capra hircus, Equus caballus)

Our first phylogeographic studies on the entire mitogenome of cattle, horse, goat and sheep provided new information on the domestication process(es). Most of the domestic species have been involved in a single domestication event that occurred in the Neolithic period (about 10,000 years ago) in the Fertile Crescent. On the contrary, the high number of haplogroups found in modern equine breeds suggests that the domestication of wild horses took place in several centres around Eurasia. The analysis is currently extended to the nuclear genome (in particular to the Y chromosome), focusing on the origin of local breeds (especially in Italy). The overall aim is to highlight parallel genetic histories of humans and domestic animals useful to further extend the current knowledge of human populations.

Collaborations: Dr. Hovirag Lancioni, Dr. Irene Cardinali, Dr. Emiliano Lasagna, Prof. Francesca Maria Sarti, Dr. Katia Cappelli, Prof. Maurizio Silvestrelli and Prof. Emidio Albertini (Univ. di Perugia); Dr. Licia Colli and Prof. Paolo Ajmone Marsan (Univ. Cattolica del S. Cuore, Piacenza).

Recent publications:

• Mitochondrial DNA variants of Podolian cattle breeds testify for a dual maternal origin (2018)
• Whole Mitogenomes Reveal the History of Swamp Buffalo: Initially Shaped by Glacial Periods and Eventually Modelled by Domestication (2017)
• An Overview of Ten Italian Horse Breeds through Mitochondrial DNA (2016)
• Survey of uniparental genetic markers in the Maltese cattle breed reveals a significant founder effect but does not indicate local domestication (2016)
• Whole mitochondrial genomes unveil the impact of domestication on goat matrilineal variability (2015)
• Mitogenomes from Egyptian Cattle Breeds: New Clues on the Origin of Haplogroup Q and the Early Spread of Bos taurus from the Near East (2015)

 

10) Genetic origins of Italian wild mammals (Sus scrofa)

The same phylogeographic approach employed to analyze the domestic species is now employed for studying the variability of some wild species that are related or depending on human activities. In particular, virtually all European wild boars belong to only one mtDNA haplogroup, named D1, with the notable exception of the Italian-specific haplogroup D4. A phylogeographic study based on complete mitogenomes is in progress to clarify the origin and spread of this “Italian” lineage.

Collaborations: Dr. Hovirag Lancioni and Dr. Francesca Vercillo (Univ. of Perugia); Dr. Massimo Scandura (Univ. of Sassari).