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Malaria History, Colonization-Related Spread Revealed in Ancient DNA Sequencing Study

Plasmodium falciparum in red blood cells

NEW YORK – An international team led by investigators at the Max Planck Institute for Evolutionary Anthropology and Harvard University has turned to ancient DNA to retrace the historical spread of Plasmodium falciparum, P. vivax, and P. malariae, uncovering signs that malaria-causing parasites moved into new parts of the world as a consequence of colonialism and the trans-Atlantic slave trade.

"Together with textual, osteological, and archaeological evidence, these new biomolecular data provide an opportunity to reassess our understanding of the past distribution of malaria parasite species," first and co-corresponding author Megan Michel, an archaeogenetics researcher affiliated with the MPI for Evolutionary Anthropology, Harvard University, and the Max Planck-Harvard Research Center for Archaeosciences of the Ancient Mediterranean, and her colleagues wrote in a paper published in Nature on Wednesday.

In an effort to overcome past challenges in finding Plasmodium DNA in ancient samples, the researchers began by screening shotgun metagenomic sequences on ancient samples from some 10,000 individuals assessed at the Max Planck Institute of Geoanthropology. They narrowed in on P. falciparum, P. vivax, or P. malariae sequences in three dozen isolates from 26 archaeological sites spanning 16 countries and going back roughly 5,500 years.

From there, the team relied on in-solution hybridization capture based on distinct bait sets to isolate and sequence nuclear and mitochondrial parasite genomes from 10 ancient cases of P. falciparum infection, 21 cases of P. vivax infection, two P. malariae-infected samples, and two cases marked by P. falciparum-P. malariae co-infection.

"Taken together, the capacity to reconstruct ancient genomes from Plasmodium [species] lays the groundwork for future studies on the origins, transmission, evolution, and cultural impact of human malaria parasites," the authors wrote.

Along with P. vivax isolates found at Middle Neolithic, Chalcolithic, and Eneolithic sites in Germany, Spain, and Russia, respectively, the researchers saw P. falciparum turning up at Iron Age sites in Central Europe as well as a high-altitude site in the Himalayan valley that has been dated at around 2,800 years old.

The latter finding "provides a rare case study in which individual mobility can be inferred from infection status," the authors suggested, "adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago."

By analyzing the newly-sequenced Plasmodium samples in combination with published genotyping data for more than 2,100 modern and 31 ancient strains of P. falciparum or P. vivax, the team further linked Plasmodium spread to documented migrations.

For example, P. vivax spread into South America appeared to involve a strain previously found in Europe, while the available data suggested P. falciparum spread to the Americas during the trans-Atlantic slave trade or during colonization by individuals from Mediterranean Europe.

"Our data underscore the role of cross-cultural contacts in the dissemination of malaria," the authors explained, "laying the biomolecular foundation for future palaeo-epidemiological research into the impact of Plasmodium parasites on human history."