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At least 649 records · Page 36Linked to original sources
PubMed1987

Latent cellular oncogenes: the paradox dissolves.

The 20 known transforming onc genes of retroviruses are defined by sequences which are transduced from cellular genes, termed proto-onc genes. Based on these sequences, viral onc genes have been postulated to be transduced cellular cancer genes and proto-onc genes have been postulated to be latent cancer genes that can be activated from within the cell, to cause virus-negative tumours. The hypothesis is popular because it promises direct access to cellular cancer genes. However the existence of latent cancer genes presents a paradox since such genes would be most undesirable for eukaryotes. The hypothesis predicts (i) that viral onc genes and proto-onc genes are isogenic, (ii) that expression of proto-onc genes induces tumours, (iii) that activated proto-onc genes transform diploid cells upon transfection, like viral onc genes, and (iv) it predicts diploid tumours. As yet, none of these predictions is confirmed. Instead: (i) Structural comparisons between viral onc genes, essential retroviral genes, and the proto-onc genes show that all viral onc genes are indeed new genes, rather than transduced cellular cancer genes. They are genetic hybrids put together from truncated viral and truncated proto-onc genes. (ii) Proto-onc genes are frequently expressed in normal cells. (iii) To date, not one activated proto-onc gene has been isolated that transforms diploid cells. (iv) Above all, no diploid tumours with activated proto-onc genes have been found. Moreover the probability of spontaneous transformation in vivo is at least 10(9) times lower than predicted from the mechanisms thought to activate proto-onc genes. Therefore the hypothesis, that proto-onc genes are latent cellular oncogenes, appears to be an over-interpretation of sequence homology to structural and functional homology with viral onc genes. Here is is proposed that only rare truncations and recombinations, that alter the germline configuration of cellular genes, generate viral and possibly cellular cancer genes. The clonal chromosome abnormalities that are consistently found in tumour cells are microscopic evidence for rearrangements that may generate cancer genes. The clonality indicates that the tumours are initiated with, and possibly by these abnormalities as predicted by Boveri in 1914.

Cell Transformation, Neoplastic↗
PubMed2006

Highly variable rates of genome rearrangements between hemiascomycetous yeast lineages.

Hemiascomycete yeasts cover an evolutionary span comparable to that of the entire phylum of chordates. Since this group currently contains the largest number of complete genome sequences it presents unique opportunities to understand the evolution of genome organization in eukaryotes. We inferred rates of genome instability on all branches of a phylogenetic tree for 11 species and calculated species-specific rates of genome rearrangements. We characterized all inversion events that occurred within synteny blocks between six representatives of the different lineages. We show that the rates of macro- and microrearrangements of gene order are correlated within individual lineages but are highly variable across different lineages. The most unstable genomes correspond to the pathogenic yeasts Candida albicans and Candida glabrata. Chromosomal maps have been intensively shuffled by numerous interchromosomal rearrangements, even between species that have retained a very high physical fraction of their genomes within small synteny blocks. Despite this intensive reshuffling of gene positions, essential genes, which cluster in low recombination regions in the genome of Saccharomyces cerevisiae, tend to remain syntenic during evolution. This work reveals that the high plasticity of eukaryotic genomes results from rearrangement rates that vary between lineages but also at different evolutionary times of a given lineage.

Candida albicans↗
PubMed1991

Expression of a novel nuclear protein in activated and in tat-I expressing T cells.

The intracellular events that occur in T lymphoid cells after activation or after infection with HIV-1 are not well defined. In the case of HIV-1 infection, it is unknown whether the tat-I gene, an essential gene for viral replication, affects host cell nuclear factors. Using two-dimensional PAGE, we have identified a novel nuclear protein, designated nuclear protein-28,000 (NP-28), which is induced in Jurkat T cells by stimulation with PMA and/or PHA or ionomycin. This nuclear protein has an apparent molecular mass of 28,000 Da and an isoelectric point of 4.6. Interestingly, Jurkat cells transfected with tat-I express higher levels of NP-28 constitutively, without added stimulation. Incubation of Jurkat cells expressing tat-I with PMA and/or PHA or ionomycin causes superinduction of NP-28. We have therefore identified a novel lymphoid nuclear protein induced by T cell activation that occurs in tat-I expressing cells in the absence of activating agents.

Genes, tat↗
PubMed2001

alpha-Adducin gene and essential hypertension in China.

Adducin is a membrane skeletal protein that is involved in the regulation of membrane ion transport and cellular signal transduction. Essential hypertension has been linked to alpha-adducin gene locus, and association of a polymorphism of the gene has been found in some studies, but results of linkage or association studies on alpha-adducin gene are controversial among different populations. This study was designed to examine the linkage between alpha-adducin gene locus and essential hypertension and to reveal the relationship between an alpha-adducin gene polymorphism (Gly460Trp) and essential hypertension in a Chinese population. For the linkage study, one hundred and six Chinese nuclear families were recruited, including 417 hypertensive patients in all 474 individuals. Those samples were genotyped at D4S412 and D4S3038. The distances between the two microsatellite markers and the alpha-adducin gene locus are less than 3cM. Parametric, non-parametric linkage (NPL) analyses using the GENEHUNTER software were carried out. Sib transmission-dise- quilibrium test (S-TDT), as well as transmission-disequilibrium test (TDT). was also implemented with TDT/S-TDT Program 1.1. Serum levels of uric acid, creatinine, blood urea nitrogen (BUN), fasting glucose and lipids were determined as phenotypes. In an association study, 138 hypertensive and 121 normotensive subjects were genotyped at Gly460Trp of the alpha-adducin gene to examine a possible association between this polymorphism and blood pressure or other phenotypes. We fail to find the linkage between the two markers and essential hypertension by parametric, NPL analysis or TDT/S-TDT study. With the use of the simple association and the multivariate logistic regression analyses, we also fail to reveal a significant association between the Gly460Trp polymorphism in alpha-adducin gene and the blood pressure variation, or blood biochemical indices studied. The frequency of the 460Trp allele in Chinese (46-48%) is similar to that found in Japanese (54-60%) while the allele frequency is less common in Caucasian (13%-23%). These findings suggest that in our Chinese population, alpha-adducin 460Trp variant may not play an important role in the etiology of EH. And the negative results of linkage and TDT/ S-TDT further supports this conclusion.

Adult↗
PubMed2004

Mili, a mammalian member of piwi family gene, is essential for spermatogenesis.

The piwi family genes, which are defined by conserved PAZ and Piwi domains, play important roles in stem cell self-renewal, RNA silencing, and translational regulation in various organisms. To reveal the function of the mammalian homolog of piwi, we produced and analyzed mice with targeted mutations in the Mili gene, which is one of three mouse homologs of piwi. Spermatogenesis in the MILI-null mice was blocked completely at the early prophase of the first meiosis, from the zygotene to early pachytene, and the mice were sterile. However, primordial germ cell development and female germ cell production were not disturbed. Furthermore, MILI bound to MVH, which is an essential factor during the early spermatocyte stage. The similarities in the phenotypes of the MILI- and MVH-deficient mice and in the physical binding properties of MILI and MVH indicate a functional association of these proteins in post-transcriptional regulation. These data indicate that MILI is essential for the differentiation of spermatocytes.

Animals↗
PubMed2006

[Correlation analysis and identification of G421C in regulatory region of CYP4F2 gene with essential hypertension].

OBJECTIVE: To investigate the correlation between G421C polymorphism in the regulatory region of CYP4F2 gene and essential hypertension and its molecular mechanism. METHODS: Totally 196 hypertensive patients (hypertension group) and 219 normotensive subjects (control group) were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The promoter activity with different alleles was evaluated by reporter assay. A Myb responsive element was identified using gel retardation assay. RESULTS: Significant differences were found in distribution of genotype and allele frequency of G421C between hypertension group and control group (P < 0.05), and homozygous GG genotype was independently associated with hypertension after adjustment for age, gender, body mass index, and other risk factors (odds ratios 1.87, 95% CI 1.11-3.13, P < 0.05). 421G reporter construct showed decreased promoter activity compared with 421C reporter construct. 421G existed in Myb responsive element, whereas 421C damaged this motif. CONCLUSION: G421C polymorphism in the regulatory region of CYP4F2 gene is correlated with essential hypertension. 421G allele inhibits transcription by binding affinity of Myb responsive element.

Adult↗
PubMed1991

The tubB alpha-tubulin gene is essential for sexual development in Aspergillus nidulans.

The filamentous fungus Aspergillus nidulans has two genes encoding alpha-tubulin, tubA and tubB. Mutational analysis of tubA has demonstrated that the tubA gene is essential for mitosis and nuclear migration. In this study we have deleted the tubB gene by replacing it with a selectable marker and have named this new allele tubB delta. The results demonstrate that the tubB gene is not required for vegetative growth or asexual reproduction, nor is it required for the initiation or early stages of sexual differentiation. Deletion of tubB, however, completely prevents ascosporogenesis, because tubB delta strains produce no sexual spores when self-crossed. These strains produce viable ascospores when outcrossed to tubB+ strains, indicating that the tubB delta mutation is recessive. We have studied the cytology of sexual development in wild-type strains and in the tubB mutant and have observed that tubB delta. strains develop normally to the stage of ascus formation. However, only a single nuclear mass is observed in the tubB delta ascus, indicating that either the two zygotic haploid nuclei are blocked in karyogamy or that karyogamy occurs but the resulting diploid nucleus is subsequently blocked in meiosis I.

Aspergillus nidulans↗
PubMed2004

Evidence against the selfish operon theory.

According to the selfish operon hypothesis, the clustering of genes and their subsequent organization into operons is beneficial for the constituent genes because it enables the horizontal gene transfer of weakly selected, functionally coupled genes. The majority of these are expected to be non-essential genes. From our analysis of the Escherichia coli genome, we conclude that the selfish operon hypothesis is unlikely to provide a general explanation for clustering nor can it account for the gene composition of operons. Contrary to expectations, essential genes with related functions have an especially strong tendency to cluster, even if they are not in operons. Moreover, essential genes are particularly abundant in operons.

Animals↗
PubMed2006

In silico analysis of Burkholderia pseudomallei genome sequence for potential drug targets.

Recent advances in DNA sequencing technology have enabled elucidation of whole genome information from a plethora of organisms. In parallel with this technology, various bioinformatics tools have driven the comparative analysis of the genome sequences between species and within isolates. While drawing meaningful conclusions from a large amount of raw material, computer-aided identification of suitable targets for further experimental analysis and characterization, has also led to the prediction of non-human homologous essential genes in bacteria as promising candidates for novel drug discovery. Here, we present a comparative genomic analysis to identify essential genes in Burkholderia pseudomallei. Our in silico prediction has identified 312 essential genes which could also be potential drug candidates. These genes encode essential proteins to support the survival of B. pseudomallei including outer-inner membrane and surface structures, regulators, proteins involved in pathogenenicity, adaptation, chaperones as well as degradation of small and macromolecules, energy metabolism, information transfer, central/intermediate/miscellaneous metabolism pathways and some conserved hypothetical proteins of unknown function. Therefore, our in silico approach has enabled rapid screening and identification of potential drug targets for further characterization in the laboratory.

Burkholderia pseudomallei↗
PubMed2006

Identification of essential operons with a rhamnose-inducible promoter in Burkholderia cenocepacia.

Scanning of bacterial genomes to identify essential genes is of biological interest, for understanding the basic functions required for life, and of practical interest, for the identification of novel targets for new antimicrobial therapies. In particular, the lack of efficacious antimicrobial treatments for infections caused by the Burkholderia cepacia complex is causing high morbidity and mortality of cystic fibrosis patients and of patients with nosocomial infections. Here, we present a method based on delivery of the tightly regulated rhamnose-inducible promoter P(rhaB) for identifying essential genes and operons in Burkholderia cenocepacia. We demonstrate that different levels of gene expression can be achieved by using two vectors that deliver P(rhaB) at two different distances from the site of insertion. One of these vectors places P(rhaB) at the site of transposon insertion, while the other incorporates the enhanced green fluorescent protein gene (e-gfp) downstream from P(rhaB). This system allows us to identify essential genes and operons in B. cenocepacia and provides a new tool for systematically identifying and functionally characterizing essential genes at the genomic level.

Burkholderia cepacia complex↗
PubMed1997

The expression of the mouse Zic1, Zic2, and Zic3 gene suggests an essential role for Zic genes in body pattern formation.

We examined the expression of Zic1, Zic2, and Zic3 genes in the mouse embryo by means of in situ hybridization. Zic genes were found as a group of genes coding for zinc finger proteins that are expressed in a restricted manner in the adult mouse cerebellum. We showed that the genes are the vertebrate homologues of Drosophila odd-paired, which may play an essential role in parasegmental subdivision and in visceral mesoderm development. The expression of the three Zic genes was first detected at gastrulation in a spatially restricted manner. At neurulation, the expression became restricted to the dorsal neural ectoderm and dorsal paraxial mesoderm. During organogenesis, the three genes were expressed in specific regions of several developing organs, including dorsal areas of the brain, spinal cord, paraxial mesenchyme, and epidermis, the marginal zone of the neural retina and distal regions of the developing limb. For all stages, significant differences in the spatial expression of Zic1, Zic2, and Zic3 were observed. Furthermore, the expression of Zic genes in Pax3, Wnt-1, and Wnt-3a mutant embryos suggested that Zic genes are not primarily regulated by the three genes which were expressed in dorsal areas similar to Zic genes. However, in open brain, a mutant with severe neural tube defects, and in the Wnt-3a mutant mice, the expression of Zic genes was changed. The changed expression pattern in Wnt-3a mutant mice suggests that Zic genes in the neural tube are regulated by the factors from notochord. Our findings suggest that Zic genes are involved in many developmental processes. Furthermore, analysis of gene expression patterns in different mouse mutants indicated that Zic genes may act upstream of many known developmental regulatory genes.

Animals↗
PubMed1981

Association between the C3F-gene and essential hypertension.

1. The complement 3 (C3) phenotype distribution in 112 patients with essential hypertension was compared with the distribution of 316 normotensive control subjects. 2. A significant increased frequency of the C3F-gene was found among the patients (0.2637 vs 0.1721, P = 0.0031), indicating an association between the C3F-gene and essential hypertension. 3. The relative risk of essential hypertension was calculated to be 1.90 for C3F-positive individuals. 4. The association between the C3F-gene and essential hypertension was stronger among the untreated patients, where a relative risk of 3.89 was found for C3F-positive subjects. 5. A significant negative correlation was found between the C3F-positivity and the severity of the hypertensive disease estimated by eye group changes. This might be in accordance with a negative natural selection of C3F-positive hypertensive patients. 6. The study supports the hypothesis that immunogenetic factors may be of pathogenetic importance in essential hypertension.

Adolescent↗
PubMed1997

Genetic analysis of sterile mutants in the dpy-5 unc-13 (I) genomic region of Caenorhabditis elegans.

Essential genes were identified in the 1.5-map unit dpy-5 unc-13 region of chromosome I in the Caenorhabditis elegans genome by rescuing lethal mutations using the duplication sDp2. In this paper, we report the mapping and complementation testing of lethal mutations, 45 of which identify 18 new, essential genes. This analysis brings the number of essential genes defined by the sDp2 rescue of lethal mutants to 97; 64 of these map between dpy-5 and unc-13. 61% of these essential genes are identified by more than one allele. Positioning of the mutations was done using the breakpoints of six duplications. The mutant phenotypes of 14 loci essential for fertility were characterized by Nomarski microscopy and DAPI staining. None of the mutants were rescued by wild-type male sperm. The cytological data showed that four genes produced mutants with defects in gonadogenesis. let-395. let-603, let-605 and let-610. Mutations in seven genes, let-355, let-367, let-384, let-513, let-544, let-545 and let-606, affected germ cell proliferation or gametogenesis. Mutants for the remaining three genes, let-370, let-599 and let-604, produced eggs that failed to develop or hatch. thereby acting as maternal effect lethals. We observed a nonrandom distribution of arrest phenotypes with regard to map position.

Alleles↗
PubMed2006

Systematic deletion and mitotic localization of the nuclear pore complex proteins of Aspergillus nidulans.

To define the extent of the modification of the nuclear pore complex (NPC) during Aspergillus nidulans closed mitosis, a systematic analysis of nuclear transport genes has been completed. Thirty genes have been deleted defining 12 nonessential and 18 essential genes. Several of the nonessential deletions caused conditional phenotypes and self-sterility, whereas deletion of some essential genes caused defects in nuclear structure. Live cell imaging of endogenously tagged NPC proteins (Nups) revealed that during mitosis 14 predicted peripheral Nups, including all FG repeat Nups, disperse throughout the cell. A core mitotic NPC structure consisting of membrane Nups, all components of the An-Nup84 subcomplex, An-Nup170, and surprisingly, An-Gle1 remained throughout mitosis. We propose this minimal mitotic NPC core provides a conduit across the nuclear envelope and acts as a scaffold to which dispersed Nups return during mitotic exit. Further, unlike other dispersed Nups, An-Nup2 locates exclusively to mitotic chromatin, suggesting it may have a novel mitotic role in addition to its nuclear transport functions. Importantly, its deletion causes lethality and defects in DNA segregation. This work defines the dramatic changes in NPC composition during A. nidulans mitosis and provides insight into how NPC disassembly may be integrated with mitosis.

Active Transport, Cell Nucleus↗
PubMed1994

Lack of association between the I/D polymorphism of the angiotensin-converting enzyme gene and essential hypertension in a Belgian population.

We tested the insertion/deletion (I/D) polymorphism of the ACE gene in 119 hypertensive patients and in 109 normotensive controls by means of the polymerase chain reaction (PCR). The allele and genotype frequencies of the I/D polymorphism in the ACE gene are essentially identical in both groups, regardless of age or sex. The I/D polymorphism of the ACE gene is thus not implicated in Belgian hypertensive patients.

Base Sequence↗
PubMed1995

QSR1, an essential yeast gene with a genetic relationship to a subunit of the mitochondrial cytochrome bc1 complex, is homologous to a gene implicated in eukaryotic cell differentiation.

Subunit 6 of the mitochondrial cytochrome bc1 complex regulates the activity of the bc1 complex in Saccharomyces cerevisiae but is not essential for respiration. To test whether QCR6, the nuclear gene which encodes subunit 6, might be functionally redundant with any other gene(s), we screened for mutations in yeast genes which are essential when the otherwise non-essential QCR6 is deleted from the yeast chromosome. We obtained such quinolcytochrome c reductase subunit-requiring mutants in two complementation groups, which we named qsr1 and qsr2. The qsr mutants require QCR6 for viability on fermentable and non-fermentable carbon sources, indicating that QCR6 is covering lethal mutations in qsr1 and qsr2, even when the yeast do not require respiration. QSR1 was cloned by rescuing the synthetic lethality of a qsr1-1 mutant. QSR1 encodes a 25.4-kDa protein which is 65% identical to a protein encoded by QM, a highly conserved human gene which has been implicated in tumorigenesis. In mammals QM is down-regulated during adipocyte, kidney, and heart differentiation, and in Nicotiana the homolog of QM is also down-regulated during differentiation. When one chromosomal copy of QSR1 was deleted in a diploid yeast strain, haploid spores derived therefrom and carrying the deletion were unable to grow on fermentable or non-fermentable carbon sources. Although QCR6 allows the qsr1-1 mutant to grow, it will not substitute for QSR1, since the deletion of QSR1 is lethal even if QCR6 is present. These results indicate a novel genetic relationship between a subunit of the mitochondrial respiratory chain and an essential gene in yeast which is homologous to a gene implicated in differentiation in other eukaryotes.

Alleles↗
PubMed1987

Rhizobium meliloti nifN (fixF) gene is part of an operon regulated by a nifA-dependent promoter and codes for a polypeptide homologous to the nifK gene product.

An essential gene for symbiotic nitrogen fixation (fixF) is located near the common nodulation region of Rhizobium meliloti. A DNA fragment carrying fixF was characterized by hybridization with Klebsiella pneumoniae nif DNA and by nucleotide sequence analysis. The fixF gene was found to be related to K. pneumoniae nifN and was therefore renamed as the R. meliloti nifN gene. Upstream of the nifN coding region a second open reading frame was identified coding for a putative polypeptide of 110 amino acids (ORF110). By fragment-specific Tn5 mutagenesis it was shown that the nifN gene and ORF110 form an operon. The control region of this operon contains a nif promoter and also the putative nifA-binding sequence. For the deduced amino acid sequence of the nifN gene product a striking homology to the R. meliloti nifK protein was found. One cysteine residue and its adjacent amino acid sequence, which are highly conserved in the R. meliloti nifK, R. meliloti nifN, and K. pneumoniae nifN proteins, may play a role in binding the FeMo cofactor.

Amino Acid Sequence↗
PubMed2003

The diversity and evolution of the T4-type bacteriophages.

Recent studies suggest that viruses are the most numerous entities in the biosphere; bacteriophages, the viruses that infect Eubacteria and Archaea, constitute a substantial fraction of this population. In spite of their ubiquity, the vast majority of phages in the environment have never been studied and nothing is known about them. For the last 10 years our research has focused on an extremely widespread group of phages, the T4-type. It has now become evident that phage T4 has a myriad of relatives in nature that differ significantly in their host range. The genomes of all these phages have homology to the T4 genes that determine virion morphology. Although phylogenetically related, these T4-type phages can be subdivided into four groups that are increasingly distant from T4: the T-evens, the pseudo T-evens, the schizo T-evens and the exo T-evens. Genomic comparisons between the various T4-type phages and T4 indicate that these genomes share homology not only for virion structural components but also for most of the essential genes involved in the T4 life cycle. This suggests that horizontal transmission of the genetic information may have played a less general role in the evolution of these phages than has been supposed. Nevertheless, we have identified several regions of the T4-type genome, such as the segment containing the tail fiber genes that exhibit evidence of extensive modular shuffling during evolution. The T4-type genomes appear to be a mosaic containing a large and fixed group of essential genes as well as highly variable set of non-essential genes. These non-essential genes are probably important for the adaptation of these phages to their particular life-style. Furthermore, swapping autonomous domains within the essential proteins may slightly modify their function(s) and contribute to the adaptive ability of the T4-type phage family. Regulatory sequences also display considerable evolutionary plasticity and this too may facilitate the adaptation of phage gene expression to new environments and stresses.

Bacteriophage T4↗