From single loci to gene networks: adaptation genomics of complex traits in human populations

Over the course of the last two decades, the advancement of technological innovations in the field of Molecular Genetics has exponentially enhanced the ability to produce immense amounts of genomic data in a short time and at a fraction of the cost that was necessary to produce a single human genome at the beginning of the current millennium. This incessant progress has also changed the methods with which human genomic data are stored and handled, as well as the power of the analyses that can be carried out, allowing for a shift from the study of single loci linked to very specific phenotypes, to the possibility of dissecting the genomic background of entire populations by managing thousands of high-quality whole genome sequences. After an introduction to the discipline of Molecular Anthropology and an overview of the dispersal of Homo sapiens from Africa, the peopling of Europe and the migratory processes that involved the Italian peninsula, this thesis showcases up-to-date investigative methods, that allow for the analysis of both whole genome sequences and SNP-array data at different levels of detail (from single nucleotide polymorphisms to single genes, to gene networks, to biological pathways). Significant original contributions to knowledge in the fields of Molecular Anthropology and Human Population Genomics are highlighted. In particular, this thesis provides novel and exciting insights into the demography and adaptation events of the Italian population, in relation to the historical and pre-historic migratory waves that contributed to the peopling of Europe and the Mediterranean. Then, it focuses on the single APOE gene, exploring its worldwide variability, evolution and its contribution to a very complex phenotype, such as human longevity. Finally, it explores the demo-evolutionary context of isolated populations in Southern Italy, revealing unexpected neurological pathways as drivers of local differentiation in an innovative analytical perspective.