ArticlePLoS computational biology2012
Evolution of the multi-domain structures of virulence genes in the human malaria parasite, Plasmodium falciparum.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Population genomics of virulence genes of Plasmodium falciparum in clinical isolates from Uganda.Scientific reports · 2017Trial
- From multiplicity of infection to force of infection in sparsely sampled high-transmissioneLife · 2026Article
- Predictive value of PfEMP1 antibody profiles for the course of controlled human malaria infections.PLoS pathogens · 2026Article
- Var genes, strain hyperdiversity, and malaria transmission dynamics.Trends in parasitology · 2025Review
- Hyper-diverse antigenic variation and resilience to transmission-reducing intervention in falciparum malaria.Nature communications · 2024Article
- Hyper-diverse antigenic variation and resilience to transmission-reducing intervention in falciparum malaria.medRxiv : the preprint server for health sciences · 2024Article
- Neutral vs. non-neutral genetic footprints of Plasmodium falciparum multiclonal infections.PLoS computational biology · 2023Article
- An antigenic diversification threshold for falciparum malaria transmission at high endemicity.PLoS computational biology · 2021Article
- Deciphering Molecular Virulence Mechanism of Mycobacterium tuberculosis Dop isopeptidase Based on Its Sequence-Structure-Function Linkage.The protein journal · 2020Article
- Controlled human malaria infection with Plasmodium falciparum demonstrates impact of naturally acquired immunity on virulence gene expression.PLoS pathogens · 2019Article
- Plasmodium knowlesi: a superb in vivo nonhuman primate model of antigenic variation in malaria.Parasitology · 2018Review
- Serological Conservation of Parasite-Infected Erythrocytes Predicts Plasmodium falciparum Erythrocyte Membrane Protein 1 Gene Expression but Not Severity of Childhood Malaria.Infection and immunity · 2016Article
- The role of PfEMP1 as targets of naturally acquired immunity to childhood malaria: prospects for a vaccine.Parasitology · 2016Review
- Global selection of Plasmodium falciparum virulence antigen expression by host antibodies.Scientific reports · 2016Article
- Differential Plasmodium falciparum surface antigen expression among children with Malarial Retinopathy.Scientific reports · 2015Article
- Maintenance of phenotypic diversity within a set of virulence encoding genes of the malaria parasite Plasmodium falciparum.Journal of the Royal Society, Interface · 2015Article
- Mastering malaria: what helps and what hurts.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- MDAT- Aligning multiple domain arrangements.BMC bioinformatics · 2015Article
- Generation of antigenic diversity in Plasmodium falciparum by structured rearrangement of Var genes during mitosis.PLoS genetics · 2014Article
- Plasmodium falciparum antigenic variation: relationships between widespread endothelial activation, parasite PfEMP1 expression and severe malaria.BMC infectious diseases · 2014Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
The var gene family of Plasmodium falciparum encodes the immunodominant variant surface antigens PfEMP1. These highly polymorphic proteins are important virulence factors that mediate cytoadhesion to a variety of host tissues, causing sequestration of parasitized red blood cells in vital organs, including the brain or placenta. Acquisition of variant-specific antibodies correlates with protection against severe malarial infections; however, understanding the relationship between gene expression and infection outcome is complicated by the modular genetic architectures of var genes that encode varying numbers of antigenic domains with differential binding specificities. By analyzing the domain architectures of fully sequenced var gene repertoires we reveal a significant, non-random association between the number of domains comprising a var gene and their sequence conservation. As such, var genes can be grouped into those that are short and diverse and genes that are long and conserved, suggesting gene length as an important characteristic in the classification of var genes. We then use an evolutionary framework to demonstrate how the same evolutionary forces acting on the level of an individual gene may have also shaped the parasite's gene repertoire. The observed associations between sequence conservation, gene architecture and repertoire structure can thus be explained by a trade-off between optimizing within-host fitness and minimizing between-host immune selection pressure. Our results demonstrate how simple evolutionary mechanisms can explain var gene structuring on multiple levels and have important implications for understanding the multifaceted epidemiology of P. falciparum malaria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.