Ancient Plasmodium genomes shed light on the history of human malaria

Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures affecting the human genome, and resistance alleles constitute biomolecular footprints outlining these species’ historical reach1. Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe1,2. To evaluate the historical global distribution of various malaria subspecies, we generated the first high-coverage ancient mitochondrial and nuclear genome-wide data from P. falciparum, P. vivax, and P. malariae from 16 countries spanning c. 5500 years of human history. We find that P. vivax and P. falciparum were present across geographically disparate regions of Eurasia as early as the fourth and first millennia BCE, respectively; in the case of P. vivax, this evidence pre-dates textual references by several millennia3. Genomic comparison between now-eliminated European and ancient and modern South and Central American strains supports distinct disease histories for P. falciparum and P. vivax in the Americas: similarities between European and peri-contact South American strains suggest European colonizers were the source of American P. vivax, while the trans-Atlantic slave trade likely introduced P. falciparum into the Americas. Our data underscore the role of cross-cultural contacts in the global dissemination of malaria parasites, laying the biomolecular foundation for future palaeoepidemiological research into the impact of Plasmodium parasites on human history. Finally, our unexpected discovery of P. falciparum in the high-altitude Himalayas provides a rare case study in which individual mobility can be inferred from infectious disease status, adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago.