Abstract:
:Malaria parasites possess the remarkable ability to maintain chronic infections that fail to elicit a protective immune response, characteristics that have stymied vaccine development and cause people living in endemic regions to remain at risk of malaria despite previous exposure to the disease. These traits stem from the tremendous antigenic diversity displayed by parasites circulating in the field. For Plasmodium falciparum, the most virulent of the human malaria parasites, this diversity is exemplified by the variant gene family called var, which encodes the major surface antigen displayed on infected red blood cells (RBCs). This gene family exhibits virtually limitless diversity when var gene repertoires from different parasite isolates are compared. Previous studies indicated that this remarkable genome plasticity results from extensive ectopic recombination between var genes during mitotic replication; however, the molecular mechanisms that direct this process to antigen-encoding loci while the rest of the genome remains relatively stable were not determined. Using targeted DNA double-strand breaks (DSBs) and long-read whole-genome sequencing, we show that a single break within an antigen-encoding region of the genome can result in a cascade of recombination events leading to the generation of multiple chimeric var genes, a process that can greatly accelerate the generation of diversity within this family. We also found that recombinations did not occur randomly, but rather high-probability, specific recombination products were observed repeatedly. These results provide a molecular basis for previously described structured rearrangements that drive diversification of this highly polymorphic gene family.
journal_name
PLoS Bioljournal_title
PLoS biologyauthors
Zhang X,Alexander N,Leonardi I,Mason C,Kirkman LA,Deitsch KWdoi
10.1371/journal.pbio.3000271subject
Has Abstractpub_date
2019-05-13 00:00:00pages
e3000271issue
5eissn
1544-9173issn
1545-7885pii
PBIOLOGY-D-19-00090journal_volume
17pub_type
杂志文章相关文献
PLOS BIOLOGY文献大全abstract::Many genes are regulated as an innate part of the eukaryotic cell cycle, and a complex transcriptional network helps enable the cyclic behavior of dividing cells. This transcriptional network has been studied in Saccharomyces cerevisiae (budding yeast) and elsewhere. To provide more perspective on these regulatory mec...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0030225
更新日期:2005-07-01 00:00:00
abstract::Over the past decade, biology has undergone a data revolution in how researchers collect data and the amount of data being collected. An emerging challenge that has received limited attention in biology is managing, working with, and providing access to data under continual active collection. Regularly updated data pr...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000125
更新日期:2019-01-29 00:00:00
abstract::Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1)-like receptors. To s...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.2004399
更新日期:2018-04-24 00:00:00
abstract::Three-dimensional (3D) structural information on many length scales is of central importance in biological research. Excellent methods exist to obtain structures of molecules at atomic, organelles at electron microscopic, and tissue at light-microscopic resolution. A gap exists, however, when 3D tissue structure needs...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0020329
更新日期:2004-11-01 00:00:00
abstract::Cellular aging, a progressive functional decline driven by damage accumulation, often culminates in the mortality of a cell lineage. Certain lineages, however, are able to sustain long-lasting immortality, as prominently exemplified by stem cells. Here, we show that Escherichia coli cell lineages exhibit comparable pa...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000266
更新日期:2019-05-23 00:00:00
abstract::Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framewo...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002394
更新日期:2016-03-02 00:00:00
abstract::One of the most influential observations in molecular evolution has been a strong association between local recombination rate and nucleotide polymorphisms across the genome. This is interpreted as evidence for ubiquitous natural selection. The alternative explanation, that recombination is mutagenic, has been rejecte...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001422
更新日期:2012-01-01 00:00:00
abstract::The acquisition of terminal cell fate and onset of differentiation are instructed by cell type-specific master control genes. Loss of differentiation is frequently observed during cancer progression, but the underlying causes and mechanisms remain poorly understood. We tested the hypothesis that master regulators of d...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1000040
更新日期:2009-02-24 00:00:00
abstract::Do malaria parasites enhance the attractiveness of humans to the parasite's vector? As such manipulation would have important implications for the epidemiology of the disease, the question has been debated for many years. To investigate the issue in a semi-natural situation, we assayed the attractiveness of 12 groups ...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0030298
更新日期:2005-09-01 00:00:00
abstract::A large repertoire of natural object manipulation tasks require precisely coupled symmetrical opposing forces by both hands on a single object. We asked how the lateralized brain handles this basic problem of spatial and temporal coordination. We show that the brain consistently appoints one of the hands as prime acto...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0040158
更新日期:2006-06-01 00:00:00
abstract::The small GTPase Rab5 is a key regulator of clathrin-mediated endocytosis. On early endosomes, within a spatially restricted domain enriched in phosphatydilinositol-3-phosphate [PI(3)P], Rab5 coordinates a complex network of effectors that functionally cooperate in membrane tethering, fusion, and organelle motility. H...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0020261
更新日期:2004-09-01 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pbio.1002436.]. ...
journal_title:PLoS biology
pub_type: 已发布勘误
doi:10.1371/journal.pbio.1002494
更新日期:2016-06-08 00:00:00
abstract::From early dinosaurs with as many as nine wrist bones, modern birds evolved to develop only four ossifications. Their identity is uncertain, with different labels used in palaeontology and developmental biology. We examined embryos of several species and studied chicken embryos in detail through a new technique allowi...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001957
更新日期:2014-09-30 00:00:00
abstract::Polarized growth is maintained by both polarized exocytosis, which transports membrane components to specific locations on the cell cortex, and endocytosis, which retrieves these components before they can diffuse away. Despite functional links between these two transport pathways, they are generally considered to be ...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002534
更新日期:2016-08-15 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pbio.2002794.]. ...
journal_title:PLoS biology
pub_type: 杂志文章,已发布勘误
doi:10.1371/journal.pbio.1002615
更新日期:2017-11-01 00:00:00
abstract::Systems biology approaches can reveal intermediary levels of organization between genotype and phenotype that often underlie biological phenomena such as polygenic effects and protein dispensability. An important conceptualization is the module, which is loosely defined as a cohort of proteins that perform a dedicated...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0040317
更新日期:2006-10-01 00:00:00
abstract::Pollen tube (PT) reception in flowering plants describes the crosstalk between the male and female gametophytes upon PT arrival at the synergid cells of the ovule. It leads to PT growth arrest, rupture, and sperm cell release, and is thus essential to ensure double fertilization. Here, we describe TURAN (TUN) and EVAN...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002139
更新日期:2015-04-28 00:00:00
abstract::Disease-associated misfolded proteins or proteins damaged due to cellular stress are generally disposed via the cellular protein quality-control system. However, under saturating conditions, misfolded proteins will aggregate. In higher eukaryotes, these aggregates can be transported to accumulate in aggresomes at the ...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0040417
更新日期:2006-12-01 00:00:00
abstract::Fusion proteins composed of the histone methyltransferase mixed-lineage leukemia (MLL) and a variety of unrelated fusion partners are highly leukemogenic. Despite their prevalence, particularly in pediatric acute leukemia, many molecular details of their transforming mechanism are unknown. Here, we provide mechanistic...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1000249
更新日期:2009-11-01 00:00:00
abstract::The intrinsic flexibility of proteins allows them to undergo large conformational fluctuations in solution or upon interaction with other molecules. Proteins also commonly assemble into complexes with diverse quaternary structure arrangements. Here we investigate how the flexibility of individual protein chains influe...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001870
更新日期:2014-05-27 00:00:00
abstract::In eukaryotic cells, most mRNAs are exported from the nucleus by the transcription export (TREX) complex, which is loaded onto mRNAs after their splicing and capping. We have studied in mammalian cells the nuclear export of mRNAs that code for secretory proteins, which are targeted to the endoplasmic reticulum membran...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0050322
更新日期:2007-12-01 00:00:00
abstract::Within the human host, the malaria parasite Plasmodium falciparum is exposed to multiple selection pressures. The host environment changes dramatically in severe malaria, but the extent to which the parasite responds to-or is selected by-this environment remains unclear. From previous studies, the parasites that cause...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.2004328
更新日期:2018-03-12 00:00:00
abstract::The signals that initiate cell invasion are not well understood, but there is increasing evidence that extracellular physical signals play an important role. Here we show that epithelial cell invasion in the intestine of zebrafish meltdown (mlt) mutants arises in response to unregulated contractile tone in the surroun...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001386
更新日期:2012-01-01 00:00:00
abstract::Ever since the discovery of neural stem cells in the mammalian brain, the possibility of brain tissue regeneration has captured the minds of scientists, clinicians, and the public. Neural stem cells have been envisioned as a source of donor cells for transplantation and vectors for the delivery of gene therapy. Over t...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.2002329
更新日期:2017-05-15 00:00:00
abstract::Copper (Cu) has emerged as an important modifier of body lipid metabolism. However, how Cu contributes to the physiology of fat cells remains largely unknown. We found that adipocytes require Cu to establish a balance between main metabolic fuels. Differentiating adipocytes increase their Cu uptake along with the ATP7...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.2006519
更新日期:2018-09-10 00:00:00
abstract::Protein kinase B (PKB/Akt) belongs to the AGC superfamily of related serine/threonine protein kinases. It is a key regulator downstream of various growth factors and hormones and is involved in malignant transformation and chemo-resistance. Full-length PKB protein has not been crystallised, thus studying the molecular...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1000017
更新日期:2009-01-20 00:00:00
abstract::Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cance...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000948
更新日期:2020-12-07 00:00:00
abstract::The oversupply of postdoctoral scholars relative to available faculty positions has led to calls for better assessment of career outcomes. Here, we report the results of a study of postdoctoral outcomes at the University of California, San Francisco, and suggest that institutions have an obligation to determine where ...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002458
更新日期:2016-05-06 00:00:00
abstract::The ability to use stored information in a highly flexible manner is a defining feature of the declarative memory system. However, the neuronal mechanisms underlying this flexibility are poorly understood. To address this question, we recorded single-unit activity from the hippocampus of 2 nonhuman primates performing...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000876
更新日期:2020-11-18 00:00:00
abstract::Although psychological and computational models of time estimation have postulated the existence of neural representations tuned for specific durations, empirical evidence of this notion has been lacking. Here, using a functional magnetic resonance imaging (fMRI) adaptation paradigm, we show that the inferior parietal...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002262
更新日期:2015-09-17 00:00:00