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The genetic analysis of ancient human remains has revolutionized the study of human history, opening a direct window onto the demographic and evolutionary events that shaped our species' past. I use state-of-the-art ancient DNA methodologies, from sample collection and DNA extraction to data analysis, to study the ancient past of the western Mediterranean region, where climate does not favour DNA preservation. After the Last Glacial Maximum, amenable climatic conditions enabled the development of agriculture in the Levant, initiating the Neolithic period. In Europe, the transition from foraging to farming was driven by the migration of people from Anatolia, but in North Africa, evidence indicates a cultural diffusion, instead of population replacement. In this thesis, I show that this transition was in fact ignited by the migration of early farmers from Iberia. Moreover, a different migration wave, originating in the Levant and expanding within Africa, was associated with pastoralism in that region during the Neolithic. While the Neolithic transition is one of the most studied periods of pre-history, earlier periods are comparatively under-studied. Using whole genome sequencing data for 36 hunter-gatherers from Iberia and France, I observed that genetic lineages rooted in the Palaeolithic, survived throught the Mesolithic. Mesolithic hunter-gatherer populations formed social units that were not based on familial bonds; exchanges between groups avoided consanguinity. Coexistence with the first farming communities resulted in unidirectional admixture patterns, as we do not find gene flow from farmers to the last hunter-gatherers. Finally, using a multidisciplinary approach to study an exceptional individual of African descent buried in a Mesolithic shell midden, we find that the burial of this man during the transatlantic slave trade period could be an example of the maintenance of African cultural practices by African people displaced to Europe. My thesis highlights the power of ancient DNA analysis to uncover events and patterns of the human evolutionary history, but also that integrative approaches, where different lines of evidence are combined, can lead to exciting findings.