Population structure and recent evolution of Plasmodium falciparum

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 duplication͞deletion 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.

Evolution of allelic dimorphism in malarial surface antigens

“…As expected for genes evolving under balancing selection, the genealogy of malaria surface antigen genes is usually deeper (Figure 2b; Hughes, 1992;Conway and Baum, 2002;Polley et al, 2005) than that of other nuclear genes within the species (Rich and Ayala, 2000;Tanabe et al, 2004;Hartl, 2004), as balancing selection tends to retain different allelic variants that otherwise would have been eliminated by random genetic drift.…”

“…Idiosyncracies of mutational patterns Rich and Ayala (2000) argued that allelic dimorphism was a likely outcome of the evolution of heterogeneous repetitive regions. In the case of Msp-2, the common P. reichenowi-P. falciparum ancestor appears to contain representatives of two repeat types, each of which dominates one of the two observed allelic classes in P. falciparum.…”

“…More recently, Polley et al (2005) provided an estimate of 27 Mya, using protein-sequence comparisons of orthologous loci in species likely to have diverged both before and after that date. As both estimates are based on alignments of highly divergent sequences, which have apparently experienced a large amount of insertion and deletion events since their divergence, aligned residues may not actually reflect homologous relationships, leading to inaccurate estimated rates of protein evolution (Rich and Ayala, 2000;Hartl et al, 2002).…”

“…Population bottleneck Rich and Ayala (2000) also examined the hypothesis that allelic dimorphism at Msp-1 of P. falciparum could reflect a recent population bottleneck from a formerly more diverse P. falciparum population, with only two distantly related alleles surviving. However, although this hypothesis offers a plausible explanation for the observation of dimorphism at a single locus, it does not predict the recurrent observation of exactly two allelic families at some loci, and thus fails to offer a general explanation for allelic dimorphism.…”

The genetic diversity of Plasmodium vivax: a review

“…have been based on P. falciparum, responsible for the most severe disease form, and on genes coding for antigenic determinants such as circumsporozoite surface protein (CSP) and merozoite surface protein (MSP). These antigenic genes are non-synonymous nucleotide polymorphisms and the multiple allelic forms differ in their ability to abrogate recognition by the host's immune response (Rich & Ayala 2000). Similar approaches have been adopted to investigate P. vivax but this species has been less well studied at the molecular level when compared to P. falciparum (Cui et al 2003).…”