The shaping of immunological responses through natural selection after the Roma Diaspora

David Comas,Mihai Ioana,Elena Bosch,Hafid Laayouni,Rob Ter Horst,Erica Bianco,Jaume Bertranpetit,Begoña Dobon,Mayukh Mondal,Mihai G Netea

doi:10.1038/s41598-020-73182-1

Abstract

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.

Highlights

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
Roma fall in a cline between European/Romanians and Indian populations, with the closest Indian populations being those geographically located in Northwest India: Rajput (RAJ), Uttar Pradesh Upper Caste Brahmins (UBR), and Punjabi (PJL)
It is at K = 4 when Roma show their own genetic component. This component can be seen in small proportions in some European populations: Romanian, Tuscans (TSI) and Iberia (IBS), areas with a known presence of Roma; and it appears in some Indian populations (RAJ, UBR, PJL, VLR and RIA)

Summary

Introduction

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. 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 assessed whole-genome sequences of both Roma individuals and individuals from the local European population of Romanians, to identify features of the genetic history of the Roma that point to the selective pressures they faced after settling in Europe. We identify several candidate immune and metabolic genes and pathways under recent positive selection in both Roma and non-Roma Romanians, arguing for a significant role of these pathways for host defense against infections prevalent on the continent during the last millennium of common habitation of these two populations

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