The Neolithic transition: signs of selection and legacy of ancient genomes in present-day Europeans

The onset of the Neolithic era, approximately 12,000 years ago, marked a pivotal period in human history, characterized by profound transformations in lifestyle, subsistence strategies, and population dynamics. The shift from a nomadic hunter-gatherer lifestyle to a sedentary one, based on agriculture and animal domestication, resulted in substantial demographic and economic reconfigurations, and introduced unprecedented selective pressures on human populations. Advancements in ancient and modern DNA analyses have enabled the identification of genomic regions subjected to strong positive selection in response to these environmental and cultural changes. The strongest signs of selection have been found on the MCM6/LCT locus, on the FADS gene cluster and on HLA region, which seem to be due respectively to processes of adaptation to famine and dairy consumption, changes in diet, and pathogen exposure. Furthermore, the expansion of early Neolithic farming groups from Southwest Asia significantly reshaped the genetic landscape of European populations. This process involved both the replacement of local hunter-gatherer groups and admixture with them, resulting in a complex mosaic of ancestries. Contemporary European populations thus exhibit heterogeneous patterns of genetic diversity, shaped by region-specific admixture proportions and ancestral contributions. These genetic patterns not only inform our understanding of human population history, but also serve as the basis for the development of ancestry-specific polygenic risk scores for complex traits.