Population structure and recent evolution of Plasmodium falciparum

Population structure and recent evolution of Plasmodium falciparum

^*Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, MA 01536; and ^†Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697

Abstract

Plasmodium falciparum is the agent of malignant malaria, one of mankind's most severe maladies. The parasite exhibits antigenic polymorphisms that have been postulated to be ancient. We have proposed that the extant world populations of P. falciparum have derived from one single parasite, a cenancestor, within the last 5,000–50,000 years. This inference derives from the virtual or complete absence of synonymous nucleotide polymorphisms at genes not involved in immune or drug responses. Seeking to conciliate this claim with extensive antigenic polymorphism, we first note that allele substitutions or polymorphisms can arise very rapidly, even in a single generation, in large populations subject to strong natural selection. Second, new alleles can arise not only by single-nucleotide mutations, but also by duplication/deletion of short simple-repeat DNA sequences, a process several orders of magnitude faster than single-nucleotide mutation. We analyze three antigenic genes known to be extremely polymorphic: Csp, Msp-1, and Msp-2. We identify regions consisting of tandem or proximally repetitive short DNA sequences, including some previously unnoticed. We conclude that the antigenic polymorphisms are consistent with the recent origin of the world populations of P. falciparum inferred from the analysis of nonantigenic genes.

Footnotes

↵ ‡ To whom reprint requests should be addressed at: Department of Ecology and Evolutionary Biology, 321 Steinhaus Hall, University of California, Irvine, CA 92697-2525. E-mail: fjayala{at}uci.edu.
This paper was presented at the National Academy of Sciences colloquium “Variation and Evolution in Plants and Microorganisms: Toward a New Synthesis 50 Years After Stebbins,” held January 27–29, 2000, at the Arnold and Mabel Beckman Center in Irvine, CA.
Data deposition: The sequences reported in this paper has been deposited in the GenBank database [accession nos. for MAD20 (X05624), 3D7 (Z35327), CAMP (X03831), PaloAlto1 (M37213), R033 (Y00087), K1 (X03371), PaloAlto2 (X15063), and WELL (A04562)].
Abbreviations:

CSP,

circumsporozoite protein;

MSP-1 and MSP-2,

merozoite surface proteins 1 and 2, respectively;

CR,

central region;

NR,

not repetitive;

RAT,

repeat allotype;

RHR,

repeat homology region