ArticlePLoS genetics2014
Generation of antigenic diversity in Plasmodium falciparum by structured rearrangement of Var genes during mitosis.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed.
- Population genomics of virulence genes of Plasmodium falciparum in clinical isolates from Uganda.Scientific reports · 2017Trial
- Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure.BMC infectious diseases · 2017Trial
- Cell cycle checkpoint activity in the malaria parasitemSphere · 2026Article
- From multiplicity of infection to force of infection in sparsely sampled high-transmissioneLife · 2026Article
- Article
- Comprehensive computational insights into Plasmodium retrocopies reveals potential roles in virulence-associated functions.Genetica · 2026Article
- Impact of GC content on de novo gene birth.Nature communications · 2026Article
- upsML: A high-accuracy machine learning classifier for predicting Plasmodium falciparum var gene upstream groups.PloS one · 2026Article
- Towards an evolutionary baseline model ofbioRxiv : the preprint server for biology · 2025Article
- Plasmodium falciparum DNA repair dynamics reveal unique roles for TLS polymerases and PfRad51 in genome diversification.Nucleic acids research · 2025Article
- Nutrient stress dramatically increases malaria parasite clag2 copy number to increase host cell permeability and enable pathogen survival.PLoS pathogens · 2025Article
- High-resolution map of the Plasmodium falciparum genome reveals MORC/ApiAP2-mediated links between distant, functionally related genes.Nature microbiology · 2025Article
- Plasmodium falciparum expresses fewer var genes at lower levels during asymptomatic dry season infections than clinical malaria cases.PLoS pathogens · 2025Article
- Var genes, strain hyperdiversity, and malaria transmission dynamics.Trends in parasitology · 2025Review
- Variable surface antigen expression, virulence, and persistent infection byMicrobiology and molecular biology reviews : MMBR · 2025Review
- A paradoxical population structure of var DBLα types in Africa.PLoS pathogens · 2025Article
- Copy Number Variations of Plasmodium vivax DBP1, EBP/DBP2, and RBP2b in Ethiopians Who Are Duffy Positive and Duffy Negative.The Journal of infectious diseases · 2024Article
- Article
- Hyper-diverse antigenic variation and resilience to transmission-reducing intervention in falciparum malaria.Nature communications · 2024Article
- GenotypingIndian journal of microbiology · 2024Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
The most polymorphic gene family in P. falciparum is the ∼60 var genes distributed across parasite chromosomes, both in the subtelomeres and in internal regions. They encode hypervariable surface proteins known as P. falciparum erythrocyte membrane protein 1 (PfEMP1) that are critical for pathogenesis and immune evasion in Plasmodium falciparum. How var gene sequence diversity is generated is not currently completely understood. To address this, we constructed large clone trees and performed whole genome sequence analysis to study the generation of novel var gene sequences in asexually replicating parasites. While single nucleotide polymorphisms (SNPs) were scattered across the genome, structural variants (deletions, duplications, translocations) were focused in and around var genes, with considerable variation in frequency between strains. Analysis of more than 100 recombination events involving var exon 1 revealed that the average nucleotide sequence identity of two recombining exons was only 63% (range: 52.7-72.4%) yet the crossovers were error-free and occurred in such a way that the resulting sequence was in frame and domain architecture was preserved. Var exon 1, which encodes the immunologically exposed part of the protein, recombined in up to 0.2% of infected erythrocytes in vitro per life cycle. The high rate of var exon 1 recombination indicates that millions of new antigenic structures could potentially be generated each day in a single infected individual. We propose a model whereby var gene sequence polymorphism is mainly generated during the asexual part of the life cycle.
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