12 research outputs found
A Tale Of Three Phytopathogens: Impact Of Transposable Elements On Genome Evolution
No full textThe genus Phytophthora harbors some notorious plant pathogens like Phytophthora infestans (causal of Irish potato famine), Phytophthora sojae (soybean rot agent), and Phytophthora ramorum (responsible for sudden oak death) that have significant economic, ecological and environmental impact. These phytopathogens exhibit remarkable phenotypic instability and vary tremendously in genome size from 65 Mb (P. ramorum) to 240 Mb (P. infestans). Complete draft genome sequences revealed that a substantial portion of their genome is occupied by highly repetitive DNA. This extreme genome plasticity is due to an infestation of repetitive virus-like genomic parasites called transposable elements (TEs). TEs are sometimes called jumping genes due to their capacity to move from one place to another in the genome. TEs are usually perceived as potent mutagens and the result of their proliferation in genome is usually detrimental, although occasionally they can contribute to the evolution of the host in a variety of ways. One such mechanism is transduplication, whereby TEs capture host gene fragments, that is known to give rise to novel genes in plants. Pathogens are in a constant arms race due to their reliance on the host to reproduce and persist and the negative fitness that they impart. Therefore, it was hypothesized that the plastic P. infestans genome allows for a rapid response to the ever-changing environment imposed by this evolutionary arms race. To this end, we have employed bioinformatics tools (RepeatScout, RepeatMasker, BLAST tools) to identify different superfamilies of TEs and assess their distribution across three Phytophthora species. Much to our surprise, we found 21 TE families carrying host genes accounting for 2.4% of the P. infestans genome. Overall, we observe a strong preference of TEs to capture genes that are involved in epigenetic regulation and critical in plant pathogenesis cycle. We report on the detailed structure of these transduplicates and their capacity to encode a functional transposase. Our results show capture of whole cellular genes by TEs and the existence of transcript evidence for the genes captured. This observed pattern of transduplication is different from what is known in plants and other species, where the capture involves gene fragments that are usually pseudogenized. Moreover, detailed analysis of the captured genes show retention of introns confirming that the transduplication events occurred at a DNA level. Cross species and molecular phylogenetic analyses further reveal that a few capture events might have predated the split of P. infestans from P. sojae and P. ramorum. Hereby, we present an in-depth analysis of various transduplication events and the impact they had in shaping the evolutionary trajectory of these phytopathogens
DINE-1, the highest copy number repeats in Drosophila melanogaster are non-autonomous endonuclease-encoding rolling-circle transposable elements (Helentrons)
No full textSingle Molecule Imaging Reveals the Functional Role of the Na+/H+ Exchanger-3 Oligomerization
No full textLoss of Diacylglycerol Kinase Epsilon in Mice Causes Endothelial Distress and Impairs Glomerular Cox-2 and Pge(2) Production
No full textThrombotic microangiopathy (TMA) is a disorder characterized by microvascular occlusion that can lead to thrombocytopenia, hemolytic anemia, and glomerular damage. Complement activation is the central event in most cases of TMA. Primary forms of TMA are caused by mutations in genes encoding components of the complement or regulators of the complement cascade. Recently, we and others have described a genetic form of TMA caused by mutations in the gene diacylglycerol kinase-epsilon (DGKE) that encodes the lipid kinase DGK(epsilon) (Lemaire M, Fremeaux-Bacchi V, Schaefer F, Choi MR, Tang WH, Le Quintrec M, Fakhouri F, Taque S, Nobili F, Martinez F, Ji WZ, Overton JD, Mane SM, Nurnberg G, Altmuller J, Thiele H, Morin D, Deschenes G, Baudouin V, Llanas B, Collard L, Majid MA, Simkova E, Nurnberg P, Rioux-Leclerc N, Moeckel GW, Gubler MC, Hwa J, Loirat C, Lifton RP. Nat Genet 45: 531-536, 2013; Ozaltin F, Li BH, Rauhauser A, An SW, Soylemezoglu O, Gonul II, Taskiran EZ, Ibsirlioglu T, Korkmaz E, Bilginer Y, Duzova A, Ozen S, Topaloglu R, Besbas N, Ashraf S, Du Y, Liang CY, Chen P, Lu DM, Vadnagara K, Arbuckle S, Lewis D, Wakeland B, Quigg RJ, Ransom RF, Wakeland EK, Topham MK, Bazan NG, Mohan C, Hildebrandt F, Bakkaloglu A, Huang CL, Attanasio M. J Am Soc Nephrol 24: 377-384, 2013). DGKe is unrelated to the complement pathway, which suggests that unidentified pathogenic mechanisms independent of complement dysregulation may result in TMA. Studying Dgke knockout mice may help to understand the pathogenesis of this disease, but no glomerular phenotype has been described in these animals so far. Here we report that Dgke null mice present subclinical microscopic anomalies of the glomerular endothelium and basal membrane that worsen with age and develop glomerular capillary occlusion when exposed to nephrotoxic serum. We found that induction of cyclooxygenase-2 and of the proangiogenic prostaglandin E-2 are impaired in Dgke null kidneys and are associated with reduced expression of the antithrombotic cell adhesion molecule platelet endothelial cell adhesion molecule-1/CD31 in the glomerular endothelium. Notably, prostaglandin E-2 supplementation was able to rescue motility defects of Dgke knockdown cells in vitro and to restore angiogenesis in a test in vivo. Our results unveil an unexpected role of Dgke in the induction of cyclooxygenase-2 and in the regulation of glomerular prostanoids synthesis under stress.Wo
Mutations In Anks6 Cause A Nephronophthisis-Like Phenotype With Esrd
No full textNephronophthisis (NPHP) is one of the most common genetic causes of CKD; however, the underlying genetic abnormalities have been established in <50% of patients. We performed genome-wide analysis followed by targeted resequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 associated with an NPHP-like phenotype. Furthermore, we identified four additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic GN, interstitial nephritis, or unknown etiology. Immunohistochemistry in human embryonic kidney tissue demonstrated that the expression patterns of ANKS6 change substantially during development. Furthermore, we detected increased levels of both total and active beta-catenin in precystic tubuli in Han:SPRD Cy/+ rats. Overall, these data indicate the importance of ANKS6 in human kidney development and suggest a mechanism by which mutations in ANKS6 may contribute to an NPHP-like phenotype in humans.WoSScopu
Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis
No full textMutations in ANKS6 cause a Nephronophthisis‐Like Phenotype with End Stage Renal Disease
No full text<p>Nephronophthisis (NPHP) is one of the most common genetic causes of chronic kidney disease (CKD); however the underlying genetic abnormalities have been established in less than 50% of cases. We performed genome-wide analysis followed by targeted re-sequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 as the cause of an NPHP-like phenotype. Furthermore, we identified 4 additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic glomerulonephritis, interstitial nephritis or unknown etiology. We demonstrated expression of ANKS6 in human embryonic kidneys and showed that both total and active β-catenin were increased in pre-cystic tubuli in Cy/+ rats, indicating strong activation of the Wnt pathway</p
