title: Plasmodium falciparum antigenic variation. Mapping mosaic var gene sequences onto a network of shared, highly polymorphic sequence blocks.
abstract: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a potentially important family of immune targets, encoded by an extremely diverse gene family called var. Understanding of the genetic organization of var genes is hampered by sequence mosaicism that results from a long history of non-homologous recombination. Here we have used software designed to analyse social networks to visualize the relationships between large collections of short var sequences tags sampled from clinical parasite isolates. In this approach, two sequences are connected if they share one or more highly polymorphic sequence blocks. The results show that the majority of analysed sequences including several var-like sequences from the chimpanzee parasite Plasmodium reichenowi can be either directly or indirectly linked together in a single unbroken network. However, the network is highly structured and contains putative subgroups of recombining sequences. The major subgroup contains the previously described group A var genes, previously proposed to be genetically distinct. Another subgroup contains sequences found to be associated with rosetting, a parasite virulence phenotype. The mosaic structure of the sequences and their division into subgroups may reflect the conflicting problems of maximizing antigenic diversity and minimizing epitope sharing between variants while maintaining their host cell binding functions.
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Coast, Kilifi, Kenya. pbull@kilifi.kemri-wellcome.org
authors.forename: Peter C
authors.initials: PC
authors.lastname: Bull
authors.forename: Caroline O
authors.initials: CO
authors.lastname: Buckee
authors.forename: Sue
authors.initials: S
authors.lastname: Kyes
authors.forename: Moses M
authors.initials: MM
authors.lastname: Kortok
authors.forename: Vandana
authors.initials: V
authors.lastname: Thathy
authors.forename: Bernard
authors.initials: B
authors.lastname: Guyah
authors.forename: José A
authors.initials: JA
authors.lastname: Stoute
authors.forename: Chris I
authors.initials: CI
authors.lastname: Newbold
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics*; D002648:Child; D017124:Conserved Sequence; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D011995:Recombination, Genetic; D016415:Sequence Alignment
chemical_list: D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum