Sequencing and genomics analysis of the eradicated European Plasmodium vivax

Although several studies have tried to reconstruct the phylogeography of Plasmodium vivax alongside human population movements, the lack of genomic information from extinct European strains has prevented a clear understanding of its spread. We used medical microscope slides prepared in 1944 from malaria-affected patients in Spain's Ebro Delta to generate the first complete genome from an eradicated European strain. Population genetics and phylogenetic analyses placed this strain as basal to a cluster including strains from the New World. This genome allowed us to calibrate a genomic mutation rate for P. vivax, and estimate the age of the last common ancestor between European and American strains to the 17th-19th century. In addition, we found that some known variants for resistance to anti-malaria drugs were already present in the European strain, predating their use. We subsequently used the genomic mutation rate to model the emergence and spread of future resistance mutations.