scholarly journals Extremely flexible infection programs in a fungal plant pathogen

2017 ◽  
Author(s):  
Janine Haueisen ◽  
Mareike Möller ◽  
Christoph J. Eschenbrenner ◽  
Jonathan Grandaubert ◽  
Heike Seybold ◽  
...  

AbstractFilamentous plant pathogens exhibit extraordinary levels of genomic variability that is proposed to facilitate rapid adaptation to changing host environments. However, the impact of genomic variation on phenotypic differentiation in pathogen populations is largely unknown. Here, we address the extent of variability in infection phenotypes of the hemibiotrophic wheat pathogen Zymoseptoria tritici by studying three field isolates collected in Denmark, Iran, and the Netherlands. These three isolates differ extensively in genome structure and gene content, but produce similar disease symptoms in the same susceptible wheat cultivar. Using advanced confocal microscopy, staining of reactive oxygen species, and comparative analyses of infection stage-specific RNA-seq data, we demonstrate considerable variation in the temporal and spatial course of infection of the three isolates. Based on microscopic observation, we determined four core infection stages: establishment, biotrophic growth, lifestyle transition, and necrotrophic growth and asexual reproduction. Comparative analyses of the fungal transcriptomes, sequenced for every infection stage, revealed that the gene expression profiles of the isolates differed significantly, and 20% of the genes are differentially expressed between the three isolates during infection. The genes exhibiting isolate-specific expression patterns are enriched in genes encoding effector candidates that are small, secreted, cysteine-rich proteins and putative virulence determinants. Moreover, the differentially expressed genes were located significantly closer to transposable elements, which are enriched for the heterochromatin-associated histone marks H3K9me3 and H3K27me3 on the accessory chromosomes. This observation indicates that transposable elements and epigenetic regulation contribute to the infection-associated transcriptional variation between the isolates. Our findings illustrate how high genetic diversity in a pathogen population can result in highly differentiated infection and expression phenotypes that can support rapid adaptation in changing environments. Furthermore, our study reveals an exceptionally high extent of plasticity in the infection program of an important wheat pathogen and shows a substantial redundancy in infection-related gene expression.Author summaryZymoseptoria tritici is a pathogen that infects wheat and induces necrosis in leaf tissue. Z. tritici field populations exhibit high levels of genetic diversity, and here we addressed the consequences of this diversity on infection phenotypes. We conducted a detailed comparison of the infection processes of three Z. tritici isolates collected in Denmark, the Netherlands, and Iran. We inoculated leaves of a susceptible wheat cultivar and monitored development of disease symptoms and infection structures in leaf tissue by confocal microscopy. The three isolates exhibited highly differentiated spatial and temporal patterns of infection, although quantitative disease was similar. Furthermore, more than 20% of the genes were differentially expressed in the three isolates during wheat infection. Variation in gene expression is particularly associated with transposable elements, suggesting a role of epigenetic regulation in transcriptional variation among the three isolates. Finally, we find that genes encoding putative virulence determinants were enriched among the differentially expressed genes, suggesting that each of the three Z. tritici isolates utilizes different strategies to manipulate host defenses. Our results emphasize that phenotypic diversity plays an important role in pathogen populations and should be considered when developing crop protection strategies.

1999 ◽  
Vol 10 (6) ◽  
pp. 1859-1872 ◽  
Author(s):  
Arnoud J. Kal ◽  
Anton Jan van Zonneveld ◽  
Vladimir Benes ◽  
Marlene van den Berg ◽  
Marian Groot Koerkamp ◽  
...  

We describe a genome-wide characterization of mRNA transcript levels in yeast grown on the fatty acid oleate, determined using Serial Analysis of Gene Expression (SAGE). Comparison of this SAGE library with that reported for glucose grown cells revealed the dramatic adaptive response of yeast to a change in carbon source. A major fraction (>20%) of the 15,000 mRNA molecules in a yeast cell comprised differentially expressed transcripts, which were derived from only 2% of the total number of ∼6300 yeast genes. Most of the mRNAs that were differentially expressed code for enzymes or for other proteins participating in metabolism (e.g., metabolite transporters). In oleate-grown cells, this was exemplified by the huge increase of mRNAs encoding the peroxisomal β-oxidation enzymes required for degradation of fatty acids. The data provide evidence for the existence of redox shuttles across organellar membranes that involve peroxisomal, cytoplasmic, and mitochondrial enzymes. We also analyzed the mRNA profile of a mutant strain with deletions of the PIP2and OAF1 genes, encoding transcription factors required for induction of genes encoding peroxisomal proteins. Induction of genes under the immediate control of these factors was abolished; other genes were up-regulated, indicating an adaptive response to the changed metabolism imposed by the genetic impairment. We describe a statistical method for analysis of data obtained by SAGE.


Blood ◽  
2009 ◽  
Vol 114 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Andrew N. Harman ◽  
Marianne Kraus ◽  
Chris R. Bye ◽  
Karen Byth ◽  
Stuart G. Turville ◽  
...  

AbstractDendritic cells (DCs) play a key role in the pathogenesis of HIV infection. HIV interacts with these cells through 2 pathways in 2 temporal phases, initially via endocytosis and then via de novo replication. Here the transcriptional response of human DCs to HIV-1 was studied in these phases and at different stages of the virus replication cycle using purified HIV-1 envelope proteins, and inactivated and viable HIV-1. No differential gene expression was detected in response to envelope. However, more than 100 genes were differentially expressed in response to entry of viable and inactivated HIV-1 in the first phase. A completely different set of genes was differentially expressed in the second phase, predominantly in response to viable HIV-1, including up-regulation of immune regulation genes, whereas genes encoding lysosomal enzymes were down-regulated. Cathepsins B, C, S, and Z RNA and protein decreased, whereas cathepsin L was increased, probably reflecting a concomitant decrease in cystatin C. The net effect was markedly diminished cathepsin activity likely to result in enhanced HIV-1 survival and transfer to contacting T lymphocytes but decreased HIV-1 antigen processing and presentation to these T cells.


2002 ◽  
Vol 81 (6) ◽  
pp. 399-405 ◽  
Author(s):  
X. Han ◽  
S. Amar

Despite their similar spindle-shaped appearance, periodontal ligament fibroblasts (PDLF) and gingival fibroblasts (GF) appear to display distinct functional activities in the maintenance of tissue integrity and during inflammatory/immune responses. We postulated that different characteristics of PDLF and GF are defined by the differential expression of specific genes. To test this, we investigated the possible variance of gene expression profile between cultured PDLF and GF, using DNA microarray technology. One hundred sixty-three genes were found differentially expressed by at least three-fold between PDLF and GF. Genes encoding transmembrane proteins and cytoskeleton-related proteins tended to be up-regulated in PDLF, whereas genes encoding cell-cycle regulation proteins and metabolism-related proteins tended to be up-regulated in GF. We concluded that PDLF and GF appear to display different gene expression patterns that may reflect intrinsic functional differences of the two cell populations and may well coordinate with their tissue-specific activities.


2020 ◽  
Author(s):  
Shahan Mamoor

We probed published and public microarray datasets (1, 2) to discover the most significant gene expression changes in the blood of patients with sepsis. We found significant induction expression of IL18RAP and IL18R1, genes encoding subunits of the interleukin-18 receptor, in whole blood from patients with sepsis.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2932-2932 ◽  
Author(s):  
Emanuela M. Ghia ◽  
Laura Z. Rassenti ◽  
Liguang Chen ◽  
Bing Cui ◽  
Christopher Deboever ◽  
...  

Abstract ROR1 is a type-1 tyrosine kinase-like orphan-receptor that ordinarily is expressed during embryogenesis, but that also is found on leukemia cells of patients (pts) with chronic lymphocytic leukemia (CLL). We identified patients with CLL cells that had negligible expression of ROR1, despite otherwise satisfying all standard criteria for diagnosis of CLL by iwCLL criteria. We performed next-generation-sequencing on the transcriptomes of 12 CLL cases that had negligible expression of ROR1 and 12 cases that expressed levels of ROR1 comparable to that typically observed in CLL. Eight of the 12 ROR1-negative cases expressed unmutated immunoglobulin heavy-chain variable region genes (IGHV) and 4 used mutated IGHV. Similarly, 7 of the 12 ROR1-positive cases used unmutated IGHV and 5 had mutated IGHV. We identified 3,094 genes that were differentially expressed between the ROR1-positive and ROR1-negative samples out of 14,761 protein-coding genes tested (DESeq2, BH-adjusted p < 0.05). Subnetwork analyses revealed 55 subnetworks that were differentially expressed between ROR1-positive and ROR1-negative cases. ROR1-positive CLL cells had higher-level expression of subnetworks associated with protein-kinase activation or proliferation of tumor cells, but lower-level expression of subnetworks associated with induction of apoptosis or RNA degradation and/or processing, than did ROR1-negative CLL cells. ROR1 and AKT1 were included in 7 subnetworks associated with proliferation, hematologic cancer, or inhibition of cell death. Fourteen (25%) of the 55 differentially expressed subnetworks previously were identified as being differentially expressed between ROR1-positve leukemias of ROR1xTCL1 transgenic mice and ROR1-negative leukemias of Eµ-TCL1-transgenic mice (see Widhopf et al, Proc Natl Acad Sci USA, 2014, PMC3896194). Gene-set enrichment analysis (GSEA) of genes encoding proteins involved in targeted signaling pathways in the BIOCARTA and Reactome database revealed that the ROR1+ leukemias had higher expression levels of genes encoding proteins in the AKT pathway than did the ROR1-negative cases. Immunoblot analysis revealed higher levels of activated pAKT relative to total AKT in representative cases of ROR1-positive CLL (8.8 ± 2.8, N = 7) than that detected in ROR1-negative CLL samples (1.0 ± 0.4, N = 4, P<0.01) (the ratios of pAKT/AKT were normalized to the mean ratio observed for ROR1-negative CLL samples); this is comparable to what we observed for ROR1-positive leukemias of ROR1xTCL1 mice, which had higher levels of activated AKT than the ROR1-negative leukemias of Eµ-TCL1 transgenic mice (Widhopf et al, Proc Natl Acad Sci USA, 2014, PMC3896194). Despite the small size of these two cohorts, it is noteworthy that the median time from diagnosis to initial therapy of the 12 patients with ROR1-negative CLL (9.4 years) was significantly longer than that noted for the 12 ROR1-positive CLL cases (2.5 years, (p < 0.01) used in this comparative analysis. In summary, this study describes a potentially new subtype of ROR1-negative CLL that has a distinctive gene expression signature and apparently indolent clinical course. Disclosures Kipps: Pharmacyclics Abbvie Celgene Genentech Astra Zeneca Gilead Sciences: Other: Advisor.


2019 ◽  
Author(s):  
Eva K Fischer ◽  
Youngseok Song ◽  
Kimberly A Hughes ◽  
Wen Zhou ◽  
Kim L Hoke

AbstractHow underlying mechanisms bias evolution toward predictable outcomes remains an area of active debate. In this study, we leveraged phenotypic plasticity and parallel adaptation across independent lineages of Trinidadian guppies (Poecilia reticulata) to assess the predictability of gene expression evolution during parallel adaptation. Trinidadian guppies have repeatedly and independently adapted to high- and low-predation environments in the wild. We combined this natural experiment with a laboratory breeding design to attribute transcriptional variation to the genetic influences of population of origin and developmental plasticity in response to rearing with or without predators. We observed substantial gene expression plasticity as well as the evolution of expression plasticity itself across populations. Genes exhibiting expression plasticity within populations were more likely to also differ in expression between populations, with the direction of population differences more likely to be opposite those of plasticity. While we found more overlap than expected by chance in genes differentially expressed between high- and low-predation populations from distinct evolutionary lineages, the majority of differentially expressed genes were not shared between lineages. Our data suggest alternative transcriptional configurations associated with shared phenotypes, highlighting a role for transcriptional flexibility in the parallel phenotypic evolution of a species known for rapid adaptation.


2018 ◽  
Author(s):  
Parvathy Krishnan ◽  
Lukas Meile ◽  
Clémence Plissonneau ◽  
Xin Ma ◽  
Fanny E. Hartmann ◽  
...  

AbstractBackgroundVariation in gene expression contributes to phenotypic diversity within species and adaptation. However, very few cases of adaptive regulatory changes have been reported and the mechanisms underlying variation in gene expression remain largely unexplored. Fungal pathogen genomes are highly plastic and harbour numerous insertions of transposable elements, which can potentially contribute to gene expression regulation. In this work we elucidated how transposable elements contribute to variation of melanin accumulation, a quantitative adaptive trait of fungal pathogens that is involved in survival under stress conditions.ResultsWe demonstrated that differential transcriptional regulation of the gene encoding the transcription factor Zmr1, which controls expression of the genes in the melanin biosynthetic gene cluster, is responsible for variation in melanin accumulation in the fungal plant pathogenZymoseptoria tritici. We show that differences in melanin levels between two strains ofZ. triticiare due to two levels of transcriptional regulation: 1) variation in the promoter sequence ofZmr1, and 2) an insertion of transposable elements upstream of theZmr1promoter. Remarkably, independent insertions of transposable elements upstream ofZmr1occurred in 9% ofZ. triticistrains from around the world and negatively regulatedZmr1expression, contributing to melanin accumulation variation.ConclusionsOur studies demonstrate that different layers of transcriptional control fine-tune the synthesis of melanin. These regulatory mechanisms potentially evolved to balance the fitness costs associated with melanin production against its positive contribution to survival in stressful environments.


2019 ◽  
Author(s):  
Elena F. Boer ◽  
Hannah F. Van Hollebeke ◽  
Sungdae Park ◽  
Carlos R. Infante ◽  
Douglas B. Menke ◽  
...  

AbstractThe tetrapod limb is a stunning example of evolutionary diversity, with dramatic variation not only among distantly related species, but also between the serially homologous forelimbs (FLs) and hindlimbs (HLs) within species. Despite this variation, highly conserved genetic and developmental programs underlie limb development and identity in all tetrapods, raising the question of how limb diversification is generated from a conserved toolkit. In some breeds of domestic pigeon, shifts in the expression of two conserved limb identity transcription factors,PITX1andTBX5, are associated with the formation of feathered HLs with partial FL identity. To determine how modulation ofPITX1andTBX5expression affects downstream gene expression, we compared the transcriptomes of embryonic limb buds from pigeons with scaled and feathered HLs. We identified a set of differentially expressed genes enriched for genes encoding transcription factors, extracellular matrix proteins, and components of developmental signaling pathways with important roles in limb development. A subset of the genes that distinguish scaled and feathered HLs are also differentially expressed between FL and scaled HL buds in pigeons, pinpointing a set of gene expression changes downstream ofPITX1andTBX5in the partial transformation from HL to FL identity. We extended our analyses by comparing pigeon limb bud transcriptomes to chicken, anole lizard, and mammalian datasets to identify deeply conservedPITX1- andTBX5-regulated components of the limb identity program. Our analyses reveal a suite of predominantly low-level gene expression changes that are conserved across amniotes to regulate the identity of morphologically distinct limbs.Summary statementIn feather-footed pigeons, mutant alleles ofPITX1andTBX5drive the partial redeployment of an evolutionarily conserved forelimb genetic program in the hindlimb.


2019 ◽  
Vol 11 (11) ◽  
pp. 3095-3105 ◽  
Author(s):  
Alice Feurtey ◽  
Danielle M Stevens ◽  
Wolfgang Stephan ◽  
Eva H Stukenbrock

Abstract Genome analyses have revealed a profound role of hybridization and introgression in the evolution of many eukaryote lineages, including fungi. The impact of recurrent introgression on fungal evolution however remains elusive. Here, we analyzed signatures of introgression along the genome of the fungal wheat pathogen Zymoseptoria tritici. We applied a comparative population genomics approach, including genome data from five Zymoseptoria species, to characterize the distribution and composition of introgressed regions representing segments with an exceptional haplotype pattern. These regions are found throughout the genome, comprising 5% of the total genome and overlapping with > 1,000 predicted genes. We performed window-based phylogenetic analyses along the genome to distinguish regions which have a monophyletic or nonmonophyletic origin with Z. tritici sequences. A majority of nonmonophyletic windows overlap with the highly variable regions suggesting that these originate from introgression. We verified that incongruent gene genealogies do not result from incomplete lineage sorting by comparing the observed and expected length distribution of haplotype blocks resulting from incomplete lineage sorting. Although protein-coding genes are not enriched in these regions, we identify 18 that encode putative virulence determinants. Moreover, we find an enrichment of transposable elements in these regions implying that hybridization may contribute to the horizontal spread of transposable elements. We detected a similar pattern in the closely related species Zymoseptoria ardabiliae, suggesting that hybridization is widespread among these closely related grass pathogens. Overall, our results demonstrate a significant impact of recurrent hybridization on overall genome evolution of this important wheat pathogen.


2006 ◽  
Vol 74 (6) ◽  
pp. 3633-3642 ◽  
Author(s):  
Sinem Beyhan ◽  
Anna D. Tischler ◽  
Andrew Camilli ◽  
Fitnat H. Yildiz

ABSTRACT Differences in whole-genome expression patterns between the classical and El Tor biotypes of Vibrio cholerae O1 were determined under conditions that induce virulence gene expression in the classical biotype. A total of 524 genes (13.5% of the genome) were found to be differentially expressed in the two biotypes. The expression of genes encoding proteins required for biofilm formation, chemotaxis, and transport of amino acids, peptides, and iron was higher in the El Tor biotype. These gene expression differences may contribute to the enhanced survival capacity of the El Tor biotype in environmental reservoirs. The expression of genes encoding virulence factors was higher in the classical than in the El Tor biotype. In addition, the vieSAB genes, which were originally identified as regulators of ctxA transcription, were expressed at a fivefold higher level in the classical biotype. We determined the VieA regulon in both biotypes by transcriptome comparison of wild-type and vieA deletion mutant strains. VieA predominantly regulates gene expression in the classical biotype; 401 genes (10.3% of the genome), including those encoding proteins required for virulence, exopolysaccharide biosynthesis, and flagellum production as well as those regulated by σE, are differentially expressed in the classical vieA deletion mutant. In contrast, only five genes were regulated by VieA in the El Tor biotype. A large fraction (20.8%) of the genes that are differentially expressed in the classical versus the El Tor biotype are controlled by VieA in the classical biotype. Thus, VieA is a major regulator of genes in the classical biotype under virulence gene-inducing conditions.


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