Ancient Plasmodium genomes shed light on the history of human malaria
Authors: Michel Megan , Skourtanioti Eirini , Pierini Federica , Guevara Evelyn K. , Mötsch Angela , Kocher Arthur , Barquera Rodrigo , Bianco Raffaela A. , Carlhoff Selina , Coppola Bove Lorenza , Freilich Suzanne , Giffin Karen , Hermes Taylor , Hiß Alina , Knolle Florian , Nelson Elizabeth A. , Neumann Gunnar U. , Papac Luka , Penske Sandra , Rohrlach Adam B. , Salem Nada , Semerau Lena , Villalba-Mouco Vanessa , Abadie Isabelle , Aldenderfer Mark , Beckett Jessica F. , Brown Matthew , Campus Franco G. R. , Chenghwa Tsang , Cruz Berrocal María , Damašek Ladislav , Duffett Carlson Kellie Sara , Durand Raphaël , Ernée Michal , Fântăneanu Cristinel , Frenzel Hannah , García Atiénzar Gabriel , Guillén Sonia , Hsieh Ellen , Karwowski Maciej , Kelvin David , Kelvin Nikki , Khokhlov Alexander , Kinaston Rebecca L. , Korolev Arkadii , Krettek Kim-Louise , Küßner Mario , Lai Luca , Look Cory , Majander Kerttu , Mandl Kirsten , Mazzarello Vittorio , McCormick Michael , de Miguel Ibáñez Patxuka , Murphy Reg , Németh Rita E. , Nordqvist Kerkko , Novotny Friederike , Obenaus Martin , Olmo-Enciso Lauro , Onkamo Päivi , Orschiedt Jörg , Patrushev Valerii , Peltola Sanni , Romero Alejandro , Rubino Salvatore , Sajantila Antti , Salazar-García Domingo C. , Serrano Elena , Shaydullaev Shapulat , Sias Emanuela , Šlaus Mario , Stančo Ladislav , Swanston Treena , Teschler-Nicola Maria , Valentin Frederique , Van de Vijver Katrien , Varney Tamara L. , Vigil-Escalera Guirado Alfonso , Waters Christopher K. , Weiss-Krejci Estella , Winter Eduard , Lamnidis Thiseas C. , Prüfer Kay , Nägele Kathrin , Spyrou Maria , Schiffels Stephan , Stockhammer Philipp W. , Haak Wolfgang , Posth Cosimo , Warinner Christina , Bos Kirsten I. , Herbig Alexander , Krause Johannes 
Published: June 2024

Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular footprints that outline the historical reach of these species1. Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe1,2. To address these questions, we generated high-coverage ancient mitochondrial and nuclear genome-wide data from P. falciparum, P. vivax and P. malariae from 16 countries spanning around 5,500 years of human history. We identified P. vivax and P. falciparum across geographically disparate regions of Eurasia from as early as the fourth and first millennia bce, respectively; for P. vivax, this evidence pre-dates textual references by several millennia3. Genomic analysis supports distinct disease histories for P. falciparum and P. vivax in the Americas: similarities between now-eliminated European and peri-contact South American strains indicate that European colonizers were the source of American P. vivax, whereas the trans-Atlantic slave trade probably introduced P. falciparum into the Americas. Our data underscore the role of cross-cultural contacts in the dissemination of malaria, laying the biomolecular foundation for future palaeo-epidemiological 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 infection status, adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago.