Evidence map›Paper›PMID 24253306›Full record

ArticleNucleic acids research2014

DNA secondary structures are associated with recombination in major Plasmodium falciparum variable surface antigen gene families.

Adam F Sander, Thomas Lavstsen, Thomas S Rask, Michael Lisby, Ali Salanti, Sarah L Fordyce, Jakob S Jespersen, Richard Carter, Kirk W Deitsch, Thor G Theander and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
5.2field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 46 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Adam F SanderCentre for Medical Parasitology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Øster Farimagsgade 5, Building 22 & 23, PO Box 2099, 1014 Copenhagen K, Denmark, Centre for Medical Parasitology, Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen K, Denmark, Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Lyngby, Denmark, Department of Biology, University of Copenhagen, Ole Maaloees Vej 5, DK-2200 Copenhagen N, Denmark, Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350 Copenhagen, Denmark, Institute of Infection and Immunology Research, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland, UK and Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.
Thomas Lavstsen
Thomas S Rask
Michael Lisby
Ali Salanti
Sarah L Fordyce
Jakob S Jespersen
Richard Carter
Kirk W Deitsch
Thor G Theander
Anders Gorm Pedersen
David E Arnot
Rigshospitalet · DKUniversity of Copenhagen · DKCopenhagen University Hospital · DKNatural History Museum of Denmark · DK

Funding

DNA repair and recombination within the var gene family of P. falciparumR01AI099327 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI DEITSCH, KIRK W · 2012 to 2016
$2.2M
NIAID NIH HHS R01 AI099327
6 · The paper itself

Abstract

Many bacterial, viral and parasitic pathogens undergo antigenic variation to counter host immune defense mechanisms. In Plasmodium falciparum, the most lethal of human malaria parasites, switching of var gene expression results in alternating expression of the adhesion proteins of the Plasmodium falciparum-erythrocyte membrane protein 1 class on the infected erythrocyte surface. Recombination clearly generates var diversity, but the nature and control of the genetic exchanges involved remain unclear. By experimental and bioinformatic identification of recombination events and genome-wide recombination hotspots in var genes, we show that during the parasite's sexual stages, ectopic recombination between isogenous var paralogs occurs near low folding free energy DNA 50-mers and that these sequences are heavily concentrated at the boundaries of regions encoding individual Plasmodium falciparum-erythrocyte membrane protein 1 structural domains. The recombinogenic potential of these 50-mers is not parasite-specific because these sequences also induce recombination when transferred to the yeast Saccharomyces cerevisiae. Genetic cross data suggest that DNA secondary structures (DSS) act as inducers of recombination during DNA replication in P. falciparum sexual stages, and that these DSS-regulated genetic exchanges generate functional and diverse P. falciparum adhesion antigens. DSS-induced recombination may represent a common mechanism for optimizing the evolvability of virulence gene families in pathogens.

Indexed as

Recombination, GeneticAntigenic VariationAntigens, ProtozoanDNA, ProtozoanGenes, ProtozoanMultigene FamilyNucleic Acid ConformationPlasmodium falciparumProtein Structure, TertiaryProtozoan ProteinsSaccharomyces cerevisiaeAntigens, ProtozoanDNA, Protozoanerythrocyte membrane protein 1, Plasmodium falciparumProtozoan Proteins

Identifiers

PMID24253306
PMCPMC3936766
OpenAlexW2012787238

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.