Evolution of allelic dimorphism in malarial surface antigens

Abstract

The extensive sequence variation in most surface antigens of Plasmodium falciparum is one of the major factors why clinical immunity to malaria develops only after repeated infections with the same species over several years. For some P. falciparum surface antigens, all observed alleles clearly fall into two allelic classes, with divergence between classes dwarfing divergence within classes. We discuss the ways in which such allelic dimorphism deviates from the expected shape of the genealogy of genes under either neutral evolution or standard balancing selection, and present a simple test, based on coalescent theory, to detect this deviation in samples of DNA sequences. We review previous hypotheses for the origin and evolution of allelic dimorphism in malarial antigens and discuss the difficulties of explaining the available data under these proposals. We conclude by offering several possible classes of explanations for allelic dimorphism, which are worthy of further theoretical and empirical exploration. © 2008 Nature Publishing Group All rights reserved.