Fig. 4.

Adaptive events evolved by ancestors of N_ITA/S_ITA clusters and their health implications for present-day Italians. The putative selective pressures having plausibly prompted local adaptations are displayed on the left, while biological processes subjected to natural selection are reported on the map along with their impact on present-day disease susceptibility. Distribution of biological adaptations having the potential to modulate the longevity phenotype (e.g., involving the mTOR signaling, arachidonic acid metabolism, and FoxO signaling pathways) in the overall Italian population, but especially in people from Southern Italy, is represented by the arrow on the right. Putative selective pressures, biological processes, and distribution of adaptations potentially modulating longevity are color-coded as follows: N_ITA, blue; S_ITA, red