The Roma people are the largest transnational ethnic minority in Europe and can be considered the last human migration of South Asian origin into the continent. They left Northwest India approximately 1,000 years ago, reaching the Balkan Peninsula around the twelfth century and Romania in the fourteenth century. Here, we analyze whole-genome sequencing data of 40 Roma and 40 non-Roma individuals from Romania. We performed a genome-wide scan of selection comparing Roma, their local host population, and a Northwestern Indian population, to identify the selective pressures faced by the Roma mainly after they settled in Europe. We identify under recent selection several pathways implicated in immune responses, among them cellular metabolism pathways known to be rewired after immune stimulation. We validated the interaction between PIK3-mTOR-HIF-1α and cytokine response influenced by bacterial and fungal infections. Our results point to a significant role of these pathways for host defense against the most prevalent pathogens in Europe during the last millennium.

罗姆人是欧洲最大的跨国少数民族，可以说是南亚裔人类最后一次进入欧洲大陆。他们大约在 1000 年前离开印度西北部，在 12 世纪左右到达巴尔干半岛，在 14 世纪到达罗马尼亚。在这里，我们分析了来自罗马尼亚的 40 名罗姆人和 40 名非罗姆人的全基因组测序数据。我们进行了全基因组选择扫描，比较了罗姆人、他们当地的宿主种群和西北部的印度种群，以确定罗姆人主要在欧洲定居后面临的选择压力。我们在最近的选择下确定了几种与免疫反应有关的途径，其中包括已知在免疫刺激后重新连接的细胞代谢途径。我们验证了 PIK3-mTOR-HIF-1α 与受细菌和真菌感染影响的细胞因子反应之间的相互作用。我们的研究结果表明，这些途径在上个千年对欧洲最流行的病原体进行宿主防御方面发挥了重要作用。