Analysis of subtelomeric virulence gene families in
            Plasmodium falciparum
            by comparative transcriptional profiling

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.

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Probing Plasmodium falciparum sexual commitment at the single-cell level

Wellcome Open Research ◽

10.12688/wellcomeopenres.14645.4 ◽

2018 ◽

Vol 3 ◽

pp. 70 ◽

Cited By ~ 14

Author(s):

Nicolas M.B. Brancucci ◽

Mariana De Niz ◽

Timothy J. Straub ◽

Deepali Ravel ◽

Lauriane Sollelis ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Life Cycle ◽

Single Cell ◽

Transcriptional Profiling ◽

Quantitative Imaging ◽

Complex Life Cycle ◽

Major Transitions ◽

Transcriptional Signature ◽

Life Cycle Stages ◽

Parasite Populations

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign.

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The Genome-Sequenced Variant of Campylobacter jejuni NCTC 11168 and the Original Clonal Clinical Isolate Differ Markedly in Colonization, Gene Expression, and Virulence-Associated Phenotypes

Journal of Bacteriology ◽

10.1128/jb.186.2.503-517.2004 ◽

2004 ◽

Vol 186 (2) ◽

pp. 503-517 ◽

Cited By ~ 141

Author(s):

Erin C. Gaynor ◽

Shaun Cawthraw ◽

Georgina Manning ◽

Joanna K. MacKichan ◽

Stanley Falkow ◽

...

Keyword(s):

Clinical Isolate ◽

Campylobacter Jejuni ◽

Transcriptional Profiling ◽

Bacterial Pathogen ◽

Gene Families ◽

Subtractive Hybridization ◽

Laboratory Culture ◽

Phenotypic Differences ◽

Culture Cells ◽

Colonization Potential

ABSTRACT The genome sequence of the enteric bacterial pathogen Campylobacter jejuni NCTC 11168 (11168-GS) was published in 2000, providing a valuable resource for the identification of C. jejuni-specific colonization and virulence factors. Surprisingly, the 11168-GS clone was subsequently found to colonize 1-day-old chicks following oral challenge very poorly compared to other strains. In contrast, we have found that the original clinical isolate from which 11168-GS was derived, 11168-O, is an excellent colonizer of chicks. Other marked phenotypic differences were also identified: 11168-O invaded and translocated through tissue culture cells far more efficiently and rapidly than 11168-GS, was significantly more motile, and displayed a different morphology. Serotyping, multiple high-resolution molecular genotyping procedures, and subtractive hybridization did not yield observable genetic differences between the variants, suggesting that they are clonal. However, microarray transcriptional profiling of these strains under microaerobic and severely oxygen-limited conditions revealed dramatic expression differences for several gene families. Many of the differences were in respiration and metabolism genes and operons, suggesting that adaptation to different oxygen tensions may influence colonization potential. This correlates biologically with our observation that anaerobically priming 11168-GS or aerobically passaging 11168-O caused an increase or decrease, respectively, in colonization compared to the parent strain. Expression differences were also observed for several flagellar genes and other less well-characterized genes that may participate in motility. Targeted sequencing of the sigma factors revealed specific DNA differences undetected by the other genomic methods. These observations highlight the capacity of C. jejuni to adapt to multiple environmental niches, the likelihood that this adaptation involves genetic evolution, and provides the first whole-genome molecular exploration of the effect of laboratory culture and storage on colonization and virulence properties of this pathogen.

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Transcriptomic Analysis of Leaf Sheath Maturation in Maize

International Journal of Molecular Sciences ◽

10.3390/ijms20102472 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2472 ◽

Cited By ~ 2

Author(s):

Lei Dong ◽

Lei Qin ◽

Xiuru Dai ◽

Zehong Ding ◽

Ran Bi ◽

...

Keyword(s):

Leaf Blade ◽

Crop Yields ◽

Transcriptional Profiling ◽

Homeobox Gene ◽

Lignin Biosynthesis ◽

Gene Families ◽

Longitudinal Axis ◽

Leaf Sheath ◽

Morphological Development ◽

Maize Leaf

The morphological development of the leaf greatly influences plant architecture and crop yields. The maize leaf is composed of a leaf blade, ligule and sheath. Although extensive transcriptional profiling of the tissues along the longitudinal axis of the developing maize leaf blade has been conducted, little is known about the transcriptional dynamics in sheath tissues, which play important roles in supporting the leaf blade. Using a comprehensive transcriptome dataset, we demonstrated that the leaf sheath transcriptome dynamically changes during maturation, with the construction of basic cellular structures at the earliest stages of sheath maturation with a transition to cell wall biosynthesis and modifications. The transcriptome again changes with photosynthesis and lignin biosynthesis at the last stage of sheath tissue maturation. The different tissues of the maize leaf are highly specialized in their biological functions and we identified 15 genes expressed at significantly higher levels in the leaf sheath compared with their expression in the leaf blade, including the BOP2 homologs GRMZM2G026556 and GRMZM2G022606, DOGT1 (GRMZM2G403740) and transcription factors from the B3 domain, C2H2 zinc finger and homeobox gene families, implicating these genes in sheath maturation and organ specialization.

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