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1.
Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification 总被引:14,自引:0,他引:14
Yanai I Benjamin H Shmoish M Chalifa-Caspi V Shklar M Ophir R Bar-Even A Horn-Saban S Safran M Domany E Lancet D Shmueli O 《Bioinformatics (Oxford, England)》2005,21(5):650-659
MOTIVATION: Genes are often characterized dichotomously as either housekeeping or single-tissue specific. We conjectured that crucial functional information resides in genes with midrange profiles of expression. RESULTS: To obtain such novel information genome-wide, we have determined the mRNA expression levels for one of the largest hitherto analyzed set of 62 839 probesets in 12 representative normal human tissues. Indeed, when using a newly defined graded tissue specificity index tau, valued between 0 for housekeeping genes and 1 for tissue-specific genes, genes with midrange profiles having 0.15< tau<0.85 were found to constitute >50% of all expression patterns. We developed a binary classification, indicating for every gene the I(B) tissues in which it is overly expressed, and the 12-I(B) tissues in which it shows low expression. The 85 dominant midrange patterns with I(B)=2-11 were found to be bimodally distributed, and to contribute most significantly to the definition of tissue specification dendrograms. Our analyses provide a novel route to infer expression profiles for presumed ancestral nodes in the tissue dendrogram. Such definition has uncovered an unsuspected correlation, whereby de novo enhancement and diminution of gene expression go hand in hand. These findings highlight the importance of gene suppression events, with implications to the course of tissue specification in ontogeny and phylogeny. AVAILABILITY: All data and analyses are publically available at the GeneNote website, http://genecards.weizmann.ac.il/genenote/ and, GEO accession GSE803. CONTACT: doron.lancet@weizmann.ac.il SUPPLEMENTARY INFORMATION: Four tables available at the above site. 相似文献
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When organisms perform a single task, selection leads to phenotypes that maximize performance at that task. When organisms need to perform multiple tasks, a trade‐off arises because no phenotype can optimize all tasks. Recent work addressed this question, and assumed that the performance at each task decays with distance in trait space from the best phenotype at that task. Under this assumption, the best‐fitness solutions (termed the Pareto front) lie on simple low‐dimensional shapes in trait space: line segments, triangles and other polygons. The vertices of these polygons are specialists at a single task. Here, we generalize this finding, by considering performance functions of general form, not necessarily functions that decay monotonically with distance from their peak. We find that, except for performance functions with highly eccentric contours, simple shapes in phenotype space are still found, but with mildly curving edges instead of straight ones. In a wide range of systems, complex data on multiple quantitative traits, which might be expected to fill a high‐dimensional phenotype space, is predicted instead to collapse onto low‐dimensional shapes; phenotypes near the vertices of these shapes are predicted to be specialists, and can thus suggest which tasks may be at play. 相似文献
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Ethan L. Sanford Kwong W. Choy Patricia K. Donahoe Adam A. Tracy Regis Hila Maria Loscertales Mauro Longoni 《PloS one》2016,11(2)
Congenital diaphragmatic hernia is associated with pulmonary hypoplasia and respiratory distress, which result in high mortality and morbidity. Although several transgenic mouse models of lung hypoplasia exist, the role of miRNAs in this phenotype is incompletely characterized. In this study, we assessed microRNA expression levels during the pseudoglandular to canalicular phase transition of normal human fetal lung development. At this critical time, when the distal respiratory portion of the airways begins to form, microarray analysis showed that the most significantly differentially expressed miRNA was miR-449a. Prediction algorithms determined that N-myc is a target of miR-449a and identified the likely miR-449a:N-myc binding sites, confirmed by luciferase assays and targeted mutagenesis. Functional ex vivo knock-down in organ cultures of murine embryonic lungs, as well as in ovo overexpression in avian embryonic lungs, suggested a role for miR-449a in distal epithelial proliferation. Finally, miR-449a expression was found to be abnormal in rare pulmonary specimens of human fetuses with Congenital Diaphragmatic Hernia in the pseudoglandular or canalicular phase. This study confirms the conserved role of miR-449a for proper pulmonary organogenesis, supporting the delicate balance between expansion of progenitor cells and their terminal differentiation, and proposes the potential involvement of this miRNA in human pulmonary hypoplasia. 相似文献
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Asaf Zviran Nofar Mor Yoach Rais Hila Gingold Shani Peles Elad Chomsky Sergey Viukov Jason D. Buenrostro Roberta Scognamiglio Leehee Weinberger Yair S. Manor Vladislav Krupalnik Mirie Zerbib Hadas Hezroni Diego Adhemar Jaitin David Larastiaso Shlomit Gilad Sima Benjamin Jacob H. Hanna 《Cell Stem Cell》2019,24(2):328-341.e9
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Steven R Fiddaman Michal Vinkler Simon G Spiro Hila Levy Christopher A Emerling Amy C Boyd Evangelos A Dimopoulos Juliana A Vianna Theresa L Cole Hailin Pan Miaoquan Fang Guojie Zhang Tom Hart Laurent A F Frantz Adrian L Smith 《Molecular biology and evolution》2022,39(1)
Penguins (Sphenisciformes) are an iconic order of flightless, diving seabirds distributed across a large latitudinal range in the Southern Hemisphere. The extensive area over which penguins are endemic is likely to have fostered variation in pathogen pressure, which in turn will have imposed differential selective pressures on the penguin immune system. At the front line of pathogen detection and response, the Toll-like receptors (TLRs) provide insight into host evolution in the face of microbial challenge. TLRs respond to conserved pathogen-associated molecular patterns and are frequently found to be under positive selection, despite retaining specificity for defined agonist classes. We undertook a comparative immunogenetics analysis of TLRs for all penguin species and found evidence of adaptive evolution that was largely restricted to the cell surface-expressed TLRs, with evidence of positive selection at, or near, key agonist-binding sites in TLR1B, TLR4, and TLR5. Intriguingly, TLR15, which is activated by fungal products, appeared to have been pseudogenized multiple times in the Eudyptes spp., but a full-length form was present as a rare haplotype at the population level. However, in vitro analysis revealed that even the full-length form of Eudyptes TLR15 was nonfunctional, indicating an ancestral cryptic pseudogenization prior to its eventual disruption multiple times in the Eudyptes lineage. This unusual pseudogenization event could provide an insight into immune adaptation to fungal pathogens such as Aspergillus, which is responsible for significant mortality in wild and captive bird populations. 相似文献
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Precise subcellular localization is an important factor in regulation of the functions of protein tyrosine phosphatases. The non-receptor form of protein tyrosine phosphatase epsilon (cyt-PTP(epsilon)) can be found in cell nuclei, among other cellular locations, while p67 PTP(epsilon), a naturally occurring isoform which lacks the 27 N terminal residues of cyt-PTP(epsilon), is exclusively cytosolic. Using deletion and scanning mutagenesis we report that the first 10 amino acid residues of cyt-PTP(epsilon), in particular residues R4, K5, and R9, are critical components for its nuclear localization. We also establish that increased oxidative stress enhances accumulation of cyt-PTP(epsilon) in cell nuclei. Of the four known protein forms of PTP(epsilon), cyt-PTP(epsilon) is the only one which includes the extreme N-terminal sequence containing R4, K5, and R9. The role of the unique N terminus of cyt-PTP(epsilon) is therefore to regulate its subcellular localization. The existence of naturally occurring forms of PTP(epsilon) which lack this sequence and which are generated by translational and posttranslational mechanisms, suggests that nuclear localization of cyt-PTP(epsilon) can be actively regulated by cells. 相似文献
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E1 and E2 are two hepatitis C viral envelope glycoproteins that assemble into a heterodimer that is essential for membrane fusion and penetration into the target cell. Both extracellular and transmembrane (TM) glycoprotein domains contribute to this interaction, but study of TM–TM interactions has been limited because synthesis and structural characterization of these highly hydrophobic segments present significant challenges. In this NMR study, by successful expression and purification of the E2 transmembrane domain as a fusion construct we have determined the global fold and characterized backbone motions for this peptide incorporated in phospholipid micelles. Backbone resonance frequencies, relaxation rates and solvent exposure measurements concur in showing this domain to adopt a helical conformation, with two helical segments spanning residues 717–726 and 732–746 connected by an unstructured linker containing the charged residues D728 and R730 involved in E1 binding. Although this linker exhibits increased local motions on the ps timescale, the dominating contribution to its relaxation is the global tumbling motion with an estimated correlation time of 12.3 ns. The positioning of the helix–linker–helix architecture within the mixed micelle was established by paramagnetic NMR spectroscopy and phospholipid-peptide cross relaxation measurements. These indicate that while the helices traverse the hydrophobic interior of the micelle, the linker lies closer to the micelle perimeter to accommodate its charged residues. These results lay the groundwork for structure determination of the E1/E2 complex and a molecular understanding of glycoprotein heterodimerization. 相似文献
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Dalit Meron Elinor Atias Lilach Iasur Kruh Hila Elifantz Dror Minz Maoz Fine Ehud Banin 《The ISME journal》2011,5(1):51-60
Rising concentrations of atmospheric carbon dioxide are acidifying the world''s oceans. Surface seawater pH is 0.1 units lower than pre-industrial values and is predicted to decrease by up to 0.4 units by the end of the century. This change in pH may result in changes in the physiology of ocean organisms, in particular, organisms that build their skeletons/shells from calcium carbonate, such as corals. This physiological change may also affect other members of the coral holobiont, for example, the microbial communities associated with the coral, which in turn may affect the coral physiology and health. In the present study, we examined changes in bacterial communities in the coral mucus, tissue and skeleton following exposure of the coral Acropora eurystoma to two different pH conditions: 7.3 and 8.2 (ambient seawater). The microbial community was different at the two pH values, as determined by denaturing gradient gel electrophoresis and 16S rRNA gene sequence analysis. Further analysis of the community in the corals maintained at the lower pH revealed an increase in bacteria associated with diseased and stressed corals, such as Vibrionaceae and Alteromonadaceae. In addition, an increase in the number of potential antibacterial activity was recorded among the bacteria isolated from the coral maintained at pH 7.3. Taken together, our findings highlight the impact that changes in the pH may have on the coral-associated bacterial community and their potential contribution to the coral host. 相似文献