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Results for “gene function”

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PubMed2000

[The relationship between gene function and virulence in alpha-herpesviruses].

Virulent alpha-herpesvirus genes, though not essential for virus replication in cell culture, play important roles in virus replication in vivo. In this paper, I classify the virulent genes and discuss the relationship between gene function and virulence. The products of the virulent genes of herpes simplex virus, described in this paper, are enzymes (thymidine kinase, ribonucleotide reductase, deoxyuridine triphosphatase, DNA polymerase, and two protein kinases), glycoproteins (gC, gE), immediate early gene product (ICP47) and gamma 34.5. To identify the virulent genes of varicellazoster virus, mutation in the Oka vaccine strain was studied. The low levels of gV expression and mutation found in the immediate early gene were predicted as the cause of the attenuation of the Oka vaccine strain.

Herpesvirus 3, Human↗

PubMed2006

A regression-based K nearest neighbor algorithm for gene function prediction from heterogeneous data.

BACKGROUND: As a variety of functional genomic and proteomic techniques become available, there is an increasing need for functional analysis methodologies that integrate heterogeneous data sources. METHODS: In this paper, we address this issue by proposing a general framework for gene function prediction based on the k-nearest-neighbor (KNN) algorithm. The choice of KNN is motivated by its simplicity, flexibility to incorporate different data types and adaptability to irregular feature spaces. A weakness of traditional KNN methods, especially when handling heterogeneous data, is that performance is subject to the often ad hoc choice of similarity metric. To address this weakness, we apply regression methods to infer a similarity metric as a weighted combination of a set of base similarity measures, which helps to locate the neighbors that are most likely to be in the same class as the target gene. We also suggest a novel voting scheme to generate confidence scores that estimate the accuracy of predictions. The method gracefully extends to multi-way classification problems. RESULTS: We apply this technique to gene function prediction according to three well-known Escherichia coli classification schemes suggested by biologists, using information derived from microarray and genome sequencing data. We demonstrate that our algorithm dramatically outperforms the naive KNN methods and is competitive with support vector machine (SVM) algorithms for integrating heterogenous data. We also show that by combining different data sources, prediction accuracy can improve significantly CONCLUSION: Our extension of KNN with automatic feature weighting, multi-class prediction, and probabilistic inference, enhance prediction accuracy significantly while remaining efficient, intuitive and flexible. This general framework can also be applied to similar classification problems involving heterogeneous datasets.

Algorithms↗

PubMed2006

On methods for gene function scoring as a means of facilitating the interpretation of microarray results.

As gene annotation databases continue to evolve and improve, it has become feasible to incorporate the functional and pathway information about genes, available in these databases into the analysis of gene expression data, for a better understanding of the underlying mechanisms. A few methods have been proposed in the literature to formally convert individual gene results into gene function results. In this paper, we will compare the various methods, propose and examine some new ones, and offer a structured approach to incorporating gene function or pathway information into the analysis of expression data. We study the performance of the various methods and also compare them on real data, using a case study from the toxicogenomics area. Our results show that the approaches based on gene function scores yield a different, and functionally more interpretable, array of genes than methods that rely solely on individual gene scores. They also suggest that functional class scoring methods appear to perform better and more consistently than overrepresentation analysis and distributional score methods.

Databases, Genetic↗

PubMed2004

Genome-wide RNAi as a route to gene function in Drosophila.

With the sequencing of the human genome and the genomes of most major model organisms completed, the systematic characterisation of gene functions remains a key challenge. During the past few years, RNA interference (RNAi) has become a powerful tool to silence the expression of genes and analyse their loss-of-function phenotype when mutant alleles are not available. Genome-wide RNAi screens against all predicted genes have been successfully used to dissect a variety of biological processes in Caenorhabditis elegans. Recently, a genome-wide library of double-stranded RNAs, that target every gene in the Drosophila genome and that is suitable for high throughput cell-based assays, was published. In this paper, recent advances will be summarised. Screening strategies and applications as a route to comprehensively characterising gene function will be discussed.

Animals↗

PubMed2002

Conservation and diversification of gene function in plant development.

The Arabidopsis genome sequence has given us an inventory of the genes needed to specify a flowering plant. Plants are highly diverse in appearance and the mechanisms whereby this diversity has arisen need explanation. A fundamental question is to what extent diversity arises from remodelling of gene function or relocation of gene pathways, rather than from the gain or loss of genes. Similar types of genetic rewiring may be responsible for both intra- and inter-specific differences in developmental processes. Recent advances in the understanding of shoot, flower and leaf development provide insights to this question.

Arabidopsis↗

PubMed1982

Determination of the order of gene function in the yeast nuclear division pathway using cs and ts mutants.

Cold-sensitive (cs) and heat-sensitive (ts) conditional-lethal mutations that affect specifically the cell division cycle of budding yeast (Saccharomyces cerevisiae) were used to determine the order of gene function. Reciprocal temperature-shift experiments using cs-ts double mutants revealed a detailed order of function among genes whose execution points and mutant phenotypes are very similar. The data suggest that the nuclear branch of the overall cell-cycle pathway itself contains at least one branch.

Cell Cycle↗

PubMed1998

PCR isolation of catechol 2,3-dioxygenase gene fragments from environmental samples and their assembly into functional genes.

A method was developed to isolate central segments of catechol 2, 3-dioxygenase (C23O) genes from environmental samples and to insert these C23O gene segments into nahH (the structural gene for C23O encoded by catabolic plasmid NAH7) by replacing the corresponding nahH sequence with the isolated segments. To PCR-amplify the central C23O gene segments, a pair of degenerate primers was designed from amino acid sequences conserved among C23Os. Using these primers, central regions of the C23O genes were amplified from DNA isolated from a mixed culture of phenol-degrading or crude oil-degrading bacteria. Both the 5' and 3' regions of nahH were also PCR-amplified by using appropriate primers. These three PCR products, the 5'-nahH and 3'-nahH segments and the central C23O gene segments, were mixed and PCR-amplified again. Since the primers for the amplification of the central C23O gene segments were designed so that the 20 nucleotides at both ends of the segments are identical to the 3' end of the 5'-nahH segment and the 5' end of the 3'-nahH segment, respectively, the central C23O gene segments could anneal to both the 5'- and 3'-nahH segments. After the second PCR, hybrid C23O genes in the form of (5'-nahH segment-central C23O gene segment-3'-nahH segment) were amplified to full length. The resulting products were cloned into a vector and used to transform Escherichia coli. This method enabled divergent C23O sequences to be readily isolated, and more than 90% of the hybrid plasmids expressed C23O activity. Thus, the present method is useful to create, without isolating bacteria, a library of functional hybrid genes.

Amino Acid Sequence↗

PubMed2006

Screening and determination of gene function using randomized ribozyme and siRNA libraries.

Rapid progress in the sequencing of the genomes of model organisms, such as the mouse, rat, nematode, fly, and Arabidopsis, as well as the human genome, has provided abundant sequence information, but functions of long stretches of these genomes remain to be determined. RNA-based technologies hold promise as tools that allow us to identify the specific functions of portions of these genomes. In particular, catalytic RNAs, known also as ribozymes, can be engineered for optimization of their activities in the intracellular environment. The introduction of a library of active ribozymes into cells, with subsequent screening for phenotypic changes, can be used for the rapid identification ofa gene function. Ribozyme technology complements another RNA-based tool for the determination of gene function, which is based on libraries of small interfering RNAs (siRNAs).

Animals↗

PubMed2005

Expression of the floral B-function gene SLM2 in female flowers of Silene latifolia infected with the smut fungus Microbotryum violaceum.

Silene latifolia is a dioecious plant in which sex is determined by X and Y chromosomes. Expression of the B-function gene SLM2, an ortholog of PISTILLATA (PI) in Arabidopsis, was examined by in situ hybridization. SLM2 was not expressed in suppressed stamens of female flowers, but was expressed in developing stamens of smut-infected female flowers. These results indicate that the control of SLM2 is independent of the presence of the Y chromosome. Smut-infected females provide a useful system for clarifying the relationship between the B-function gene and the sex determination factor.

Arabidopsis Proteins↗

PubMed1995

Conservation of floral homeotic gene function between Arabidopsis and antirrhinum.

Several homeotic genes controlling floral development have been isolated in both Antirrhinum and Arabidopsis. Based on the similarities in sequence and in the phenotypes elicited by mutations in some of these genes, it has been proposed that the regulatory hierarchy controlling floral development is comparable in these two species. We have performed a direct experimental test of this hypothesis by introducing a chimeric Antirrhinum Deficiens (DefA)/Arabidopsis APETALA3 (AP3) gene, under the control of the Arabidopsis AP3 promoter, into Arabidopsis. We demonstrated that this transgene is sufficient to partially complement severe mutations at the AP3 locus. In combination with a weak ap3 mutation, this transgene is capable of completely rescuing the mutant phenotype to a fully functional wild-type flower. These observations indicate that despite differences in DNA sequence and expression, DefA coding sequences can compensate for the loss of AP3 gene function. We discuss the implications of these results for the evolution of homeotic gene function in flowering plants.

Arabidopsis↗

PubMed2002

[A high-efficiency method of sorting and sequencing of functional genes].

The implementation of the Human Genome Project preludes the analyzing of biologic genomes. Following the successful analysis of diverse biologic genomes, it becomes more and more important to research the functions of genes and to find new functional genes. In this article, we use the techniques of Megaclone, Megasort and MPSS to sort and sequence effectively different functional genes.

English Abstract↗

PubMed1998

Indigo: a World-Wide-Web review of genomes and gene functions.

The present article describes a genome database reviewing gene-related knowledge of two model bacteria, Bacillus subtilis and Escherichia coli. The database, Indigo, is open through the World-Wide Web (http://indigo.genetique.uvsq.fr). The concept used for organising the data, the concept of neighbourhood, allows one to explore the database content in an efficient although somewhat unusual way. Here, genes are related to each other by a variety of neighbourhoods, including proximity in the chromosome, phylogenetic kinship, participation in a common metabolic pathway, common presence in an article of the literature, or similar use of the genetic code. Several examples illustrate how this concept of neighbourhood permits one to review the available knowledge about a given gene or gene family, and elaborate unexpected, but revealing, analyses about gene functions.

Bacillus subtilis↗

PubMed1995

Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: functional redundancy among physiological plasminogen activators.

Several lines of indirect evidence suggest that plasminogen activation plays a crucial role in degradation of the follicular wall during ovulation. However, single-deficient mice lacking tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), or PA inhibitor type 1(PAI-1) gene function were recently found to have normal reproduction, although mice with a combined deficiency of tPA and uPA were significantly less fertile. To investigate whether the reduced fertility of mice lacking PA gene function is due to a reduced ovulation mechanism, we have determined the ovulation efficiency in 25-day-old mice during gonadotropin-induced ovulation. Our results reveal that ovulation efficiency is normal in mice with a single deficiency of tPA or uPA but reduced by 26% in mice lacking both physiological PAs. This result suggests that plasminogen activation plays a role in ovulatory response, although neither tPA nor uPA individually or in combination is obligatory for ovulation. The loss of an individual PA seems to be functionally complemented by the remaining PA but this compensation does not appear to involve any compensatory up-regulation. Our data imply that a functionally redundant mechanism for plasmin formation operates during gonadotropin-induced ovulation and that PAs together with other proteases generate the proteolytic activity required for follicular wall degradation.

Animals↗

PubMed1999

The biosynthetic gene cluster for the 26-membered ring polyene macrolide pimaricin. A new polyketide synthase organization encoded by two subclusters separated by functionalization genes.

The biosynthetic gene cluster for the 26-membered ring of the polyene macrolide pimaricin extends for about 110 kilobase pairs of contiguous DNA in the genome of Streptomyces natalensis. Two sets of polyketide synthase (PKS) genes are separated by a group of small polyketide-functionalizing genes. Two of the polyketide synthase genes, pimS0 and pimS1, have been fully sequenced and disrupted proving the involvement of each of these genes in pimaricin biosynthesis. The pimS0 gene encodes a relatively small acetate-activating PKS (approximately 193 kDa) that appears to work as a loading protein which "presents" the starter unit to the second PKS subunit. The pimS1 gene encodes a giant multienzyme (approximately 710 kDa) harboring 15 activities responsible for the first four cycles of chain elongation in pimaricin biosynthesis, resulting in formation of the polyene chromophore.

Amino Acid Sequence↗

PubMed1989

Human non-histone chromosomal protein HMG-17: identification, characterization, chromosome localization and RFLPs of a functional gene from the large multigene family.

The multigene family of chromosomal protein HMG-17 is the largest known human retropseudogene family. A functional gene was identified and isolated by screening cDNA-selected genomic clones with a set of 5 oligonucleotides whose sequence corresponded to regions in which the sequence of the retropseudogenes differed from that of the cDNA and which did not span previously identified exon/intron junctions. A 7195 bp genomic fragment containing 6 exons, ranging in size from 30 to 817 bp, two of which encode the entire DNA binding domain of the protein, was sequenced. The gene has features which are typical to "housekeeping" genes and is characterized by a very high content of G + C residues in a 1.4 kb fragment starting 500 bp from the cap site and by an "HTF" island in the 5' region. Transcriptional regulatory signals, exon/intraon boundaries and features characteristic of "housekeeping" genes are evolutionary conserved between the human and chicken genes. The HMG-17 gene was localized to human chromosome 1p12-34. RFLP's useful for further mapping were detected. The experimental evidence presented leads to the assumption that the gene characterized is the only functional human HMG-17 gene.

Amino Acid Sequence↗

PubMed2004

A systemic gene silencing method suitable for high throughput, reverse genetic analyses of gene function in fern gametophytes.

BACKGROUND: Ceratopteris richardii is a useful experimental system for studying gametophyte development and sexual reproduction in plants. However, few tools for cloning mutant genes or disrupting gene function exist for this species. The feasibility of systemic gene silencing as a reverse genetics tool was examined in this study. RESULTS: Several DNA constructs targeting a Ceratopteris protoporphyrin IX magnesium chelatase (CrChlI) gene that is required for chlorophyll biosynthesis were each introduced into young gametophytes by biolistic delivery. Their transient expression in individual cells resulted in a colorless cell phenotype that affected most cells of the mature gametophyte, including the meristem and gametangia. The colorless phenotype was associated with a 7-fold decrease in the abundance of the endogenous transcript. While a construct designed to promote the transient expression of a CrChlI double stranded, potentially hairpin-forming RNA was found to be the most efficient in systemically silencing the endogenous gene, a plasmid containing the CrChlI cDNA insert alone was sufficient to induce silencing. Bombarded, colorless hermaphroditic gametophytes produced colorless embryos following self-fertilization, demonstrating that the silencing signal could be transmitted through gametogenesis and fertilization. Bombardment of young gametophytes with constructs targeting the Ceratopteris filamentous temperature sensitive (CrFtsZ) and uroporphyrin dehydrogenase (CrUrod) genes also produced the expected mutant phenotypes. CONCLUSION: A method that induces the systemic silencing of target genes in the Ceratopteris gametophyte is described. It provides a simple, inexpensive and rapid means to test the functions of genes involved in gametophyte development, especially those involved in cellular processes common to all plants.

Arabidopsis Proteins↗

PubMed2004

Molecular analysis of bacterial community based on 16S rDNA and functional genes in activated sludge enriched with 2,4-dichlorophenoxyacetic acid (2,4-D) under different cultural conditions.

Differential emergence and diversity of bacterial communities from activated sludge in response to varied cultural conditions using 2,4-dichlorophenoxyacetic acid (2,4-D) were investigated by coupling molecular analyses based on 16S rDNA with functional genes. We employed three different cultural conditions: (1) a culture sequentially fed a high concentration (300 mg/L) of 2,4-D (HS); (2) a culture continuously fed a low concentration (10 mg/L) of 2,4-D (LC); and (3) a serial batch culture in which 1% (v/v) of culture was transferred to a fresh medium containing a high concentration (300 mg/L) of 2,4-D (HB). The HS and LC bioreactors were operated for 3 months and HB was repeatedly transferred for 1 month. The 2,4-D was stably degraded under all the cultural conditions tested. PCR amplification and cloning-based analysis of functional genes using community DNAs from the cultures revealed five different oxygenase genes that may be involved in the initial step of 2,4-D degradation. All five gene-types were present in HS, while one of the five genes, type V (tftA) was not detected in LC. Quantitative PCR analysis showed that in HS, Ralstonia eutropha JMP 134 type-tfdA4 (type I) was the most abundant in copy number (2.0 +/- 0.1 x 10(7) copies/microg DNA) followed by RASC type-tfdA (type II) (1.8 +/- 1.0 x 10(6) copies/microg DNA), putative cadA-like gene (type IV) (2.6 +/- 0.8 x 10(5) copies/microg DNA), cadA gene (type III) (1.3 +/- 1.0 x 10(4) copies/microg DNA), and tftA gene (type V) (3.5 +/- 1.1 x 10(3) copies/microg DNA). Similar results were obtained in LC. In contrast, HB contained only type I and type III genes, and the type I gene was five orders of magnitude greater in copy number than the type III gene. Denaturing gel gradient electrophoresis (DGGE) analysis of PCR, amplified 16S rDNA fragments of bacterial communities in the three different cultures showed low similarity coefficient values (< or =0.35) when compared to the original activated sludge, suggesting that 2,4-D amendment caused a drastic change in the bacterial community. Particularly, HB showed only six bands (16-18 bands in the other cultures) and very low similarity coefficient values when compared to the other communities (0.10 to HS, 0.17 to LC, and 0.0 to original sludge). These results indicated that serial batch culturing (HB) resulted in a phylogenetically limited number of 2,4-D degrading bacteria carrying limited catabolic genes whereas more diverse 2,4-D degraders and catabolic genes were present in HS and LC. Therefore, the approach used for monitoring should be taken into account when one evaluates the population dynamics of contaminant-degrading bacteria at bioremediation sites.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1987

Activation of latent herpes simplex virus type 2 infection in vitro requires a (E)-5-(2-bromovinyl)-2'-deoxyuridine-sensitive gene function.

Previous studies have shown that herpes simplex virus (HSV) type 2 (HSV-2) can be maintained in a latent state in a limited number of cells by elevating the incubation temperature after treatment of HSV-infected human fetus lung fibroblast cells with metabolic inhibitors. Superinfection with human cytomegalovirus (HCMV) of latently infected cells maintained at the elevated temperature reactivated latent virus. In addition, superinfection with temperature-sensitive mutants indicated that reactivation of latent HSV in vitro did not require the expression of late gene function(s) of the superinfecting virus. We now report the (i) design of an in vitro HSV-2-latency system in which a higher percentage of cells contain a virus genome that can be activated; and (ii) subsequent use of this system to further characterize the virus activation process. Superinfection with a transcription-negative temperature-sensitive mutant of HSV type 1 (HSV-1) did not reactivate HSV-2-replication, suggesting that adsorption and penetration of the superinfecting virus were not sufficient for reactivation of the latent virus. Furthermore, superinfection with HSV-1 in the presence of (E)-5-(2-bromovinyl)-2'-deoxyuridine did not reactivate HSV-2 replication, suggesting that the expression of the immediate-early gene products are not sufficient for HSV-2 reactivation. Collectively, these data suggest that in addition to the expression of immediate-early gene function(s) at least a subset of early HSV-1 gene products are required for reactivation of latent HSV-2 in vitro.

Antiviral Agents↗