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It has been proposed that the acquisition of Plasmodium falciparum by man is a relatively recent event and that the sustained presence of this disease in man is unlikely to have been possible prior to the establishment of agriculture. To establish phylogenetic relationships among the Plasmodium species and to unravel the mystery of the origin of P. falciparum, we have analyzed and compared phylogenetically the small-subunit ribosomal RNA gene sequences of the species of malaria that infect humans as well as a number of those sequences from species that infect animals. Although this comparison confirmed the three established major subgroups, broadly classed as avian, simian, and rodent, we find that the human pathogen P. falciparum is monophyletic with the avian subgroup, indicating that P. falciparum and avian parasites share a relatively recent avian progenitor. The other important human pathogen, P. vivax, is very similar to a representative of the simian group of Plasmodium. The relationship between P. falciparum and the avian parasites, and the overall phylogeny of the genus, provides evidence of an exception to Farenholz's rule, which propounds synchronous speciation between host and parasite.

Plasmodium falciparum appears to have arisen as a result of lateral transfer between avian and human hosts.