The origin and geographical spread of Plasmodium falciparum is here determi
ned by analysis of mitochondrial DNA sequence polymorphism and divergence f
rom its most closely related species P. reichenowi (a rare parasite of chim
panzees). The complete 6 kb mitochondrial genome was sequenced from the sin
gle known isolate of P. reichenowi and from four different cultured isolate
s of P. falciparum, and aligned with the two previously derived P. falcipar
um sequences. The extremely low synonymous nucleotide polymorphism in P. fa
lciparum (pi = 0.0004) contrasts with the divergence at such sites between
the two species (K = 0.1201), and supports a hypothesis that P. falciparum
has recently emerged from a single ancestral population. To survey the geog
raphical distribution of mitochondrial haplotypes in P. falciparum, 104 iso
lates from several endemic areas were typed for each of the identified sing
le nucleotide polymorphisms. The haplotypes show a radiation out of Africa,
with unique types in Southeast Asia and South America being related to Afr
ican types by single nucleotide changes. This indicates that P. falciparum
originated in Africa and colonised Southeast Asia and South America separat
ely. (C) 2000 Elsevier Science B.V. All rights reserved.