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Results for “Functional genes”

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At least 73 records · Page 4Linked to original sources

PubMed2005

An adaptive radiation model for the origin of new gene functions.

Current models for the evolution of new gene functions after gene duplication presume that the duplication events themselves have no effect on fitness. But those duplications that result in new gene functions are likely to be positively selected from their inception. The evolution of new function may start with the amplification of an existing gene with some level of preadaptation for that function, followed by a period of competitive evolution among the gene copies, resulting in the preservation of the most effective variant and the 'pseudogenization' and eventual loss of the rest.

Adaptation, Physiological↗

PubMed2000

Elucidating tumor necrosis factor signaling pathway using a functional gene identification approach.

Functional identification of genes is an efficient way to study many biological processes in lower eukaryotes. However, an effective approach in mammalian cells is still under development. We designed a functional gene identification procedure and applied it in a study of tumor necrosis factor (TNF)-induced cell killing. This procedure employed a specially designed retroviral vector that allows random truncation of genes, efficiently selecting clones in which a gene was disrupted and quickly identifying disrupted genes. We have identified several novel genes by a preliminary test of this approach and confirmed by reconstitution that the genes we identified are required for TNF cytotoxicity in L929 cells. Because of the efficient identification of these components in TNF-induced cell killing, we have already been able to outline the killing pathway of TNF in L929 cells. Application of this method could be widespread because it can be used in studying any cellular responses if a specific selection assay can be set up.

Animals↗

PubMed1996

[Androgen receptor gene structure and protein function. Gene structural defects that promote androgen resistance in men].

The human androgen receptor is a member of the superfamily of steroid hormone receptors and contains three functional domains: an amino-terminal region involved in the expression of androgen regulated genes, a central cysteine-rich DNA binding region and a carboxy-terminal hormone binding region. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. Androgen action is currently studied in vitro, using fibroblasts culture from genital skin and complementary DNA of the androgen receptor gene has been recently cloned and sequenced. During recent years a substantial progress has been made elucidating the structure-function relationship of the androgen receptor and the characterization of the molecular defects associated with androgen insensitivity syndromes. There appears to be a broad correlation between the degree of receptor dysfunction caused by the mutation and the patient phenotype.

Genes↗

PubMed2001

Characterization of three GLOBOSA-like MADS-box genes from maize: evidence for ancient paralogy in one class of floral homeotic B-function genes of grasses.

Floral homeotic B-function genes are involved in specifying the identity of petals and stamens during flower development in higher eudicotyledonous plants. Monocotyledonous plants belonging to the grass family (Poaceae) have very similar B-function genes, except that these genes specify lodicules rather than petals. All B-function genes known so far are members of the MADS-box gene family encoding transcription factors. In some eudicot model systems such as Arabidopsis and Antirrhinum, the B-function is provided by heterodimeric protein complexes encoded by one DEF- and one GLO-like gene. In several different lineages of flowering plant species, however, more than one DEF- or GLO-like gene is found. A known example is the monocot model system rice, which contains two GLO-like genes, termed OSMADS2 and OSMADS4. Duplications of floral homeotic genes may have played a critical role in the diversification of floral homeotic functions and thus the evolution of flowers. In order to date the gene duplication event that gave rise to these two genes, we cloned cDNAs of three different GLO-like genes from maize, a distant relative of rice within the Poaceae family. Phylogeny reconstructions and chromosomal mapping indicate that one of these genes, named ZMM16, is orthologous to OSMADS2, and that the other two, ZMM18 and ZMM29, are probably orthologous to OSMADS4. The gene duplication which gave rise to OSMADS2- and OSMADS4-like genes occurred probably after the split of the lineages that resulted in extant Liliaceae and Poaceae, but before the separation of the lineages that gave rise to extant maize and rice about 50 MYA. Northern and in situ hybridization studies demonstrated that the maize genes are expressed in lodicules, stamens and carpels throughout spikelet development in male and female inflorescences. The GLO-like genes from rice have very similar patterns of mRNA accumulation. In addition, ZMM16 shows also weak expression in vegetative organs. Conservation of the expression in lodicules and stamens is in perfect agreement with a floral homeotic B-function of the GLO-like genes in grasses. The conserved expression in carpels is discussed. Moreover, circumstantial evidence for a functional diversification of GLO-like genes in grasses is provided.

Amino Acid Sequence↗

PubMed2002

A functional gene discovery in cell differentiation by hybrid ribozyme and siRNA libraries.

Recently, we developed a gene discovery system that can identify functional genes using a randomized hybrid ribozyme library. In this system, inhibition of the expression of a particular gene by active ribozymes was reflected by a change in a particular phenotype, the method allowed the identification of functional genes. In the case of identification of functional genes for apoptosis pathways, we identified many pro-apoptotic genes in TNF-alpha and Fas-mediated apoptosis pathways. In this study, we tried to identify the functional genes that are necessary for the retinoic acid (RA)-induced cell differentiation using randomized ribozyme and siRNA libraries. We succeeded to identify the several differentiation factors. Therefore, our gene discovery system based on randomized ribozyme and siRNA libraries are high potential to identify the differentiation and undifferentiation factors in the post genome era.

Cell Differentiation↗

PubMed2004

Comparison of two schemes for automatic keyword extraction from MEDLINE for functional gene clustering.

One of the key challenges of microarray studies is to derive biological insights from the unprecedented quatities of data on gene-expression patterns. Clustering genes by functional keyword association can provide direct information about the nature of the functional links among genes within the derived clusters. However, the quality of the keyword lists extracted from biomedical literature for each gene significantly affects the clustering results. We extracted keywords from MEDLINE that describes the most prominent functions of the genes, and used the resulting weights of the keywords as feature vectors for gene clustering. By analyzing the resulting cluster quality, we compared two keyword weighting schemes: normalized z-score and term frequency-inverse document frequency (TFIDF). The best combination of background comparison set, stop list and stemming algorithm was selected based on precision and recall metrics. In a test set of four known gene groups, a hierarchical algorithm correctly assigned 25 of 26 genes to the appropriate clusters based on keywords extracted by the TDFIDF weighting scheme, but only 23 og 26 with the z-score method. To evaluate the effectiveness of the weighting schemes for keyword extraction for gene clusters from microarray profiles, 44 yeast genes that are differentially expressed during the cell cycle were used as a second test set. Using established measures of cluster quality, the results produced from TFIDF-weighted keywords had higher purity, lower entropy, and higher mutual information than those produced from normalized z-score weighted keywords. The optimized algorithms should be useful for sorting genes from microarray lists into functionally discrete clusters.

Artificial Intelligence↗

PubMed1999

Full length cDNA cloning, promoter sequence, and genomic organization of the human adrenoleukodystrophy related (ALDR) gene functionally redundant to the gene responsible for X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is a functional defect of the ALD Protein (ALDP), an ABC half-transporter localized in the peroxisomal membrane. It is characterized by defective, very long chain fatty acid (VLCFA) beta-oxidation, resulting in progressive cerebral demyelination. Since individual mutations in the ALD gene may result in a variety of clinical phenotypes, the existence of modifying genetic factors has been proposed. The adrenoleukodystrophy related protein (ALDRP), a close homolog of ALDP, has been shown to complement the defect of VLCFA oxidation if transfected into X-ALD cells or chemically induced in ALDP-deficient mice. Chemical ALDRP induction holds a potential for a novel therapeutic strategy. We report here the exclusively peroxisomal localization of human ALDRP, the full length cDNA, the transcriptional start, and 2.4 kb of the putative promoter region DNA sequence. The human ALDR gene extends over 33 kb on chromosome 12q12 and consists of 10 exons. The gene structure is highly similar to the ALD gene, indicating a recent divergence from a common ancestor. The putative human promoter sequence contains a novel motif conserved in peroxisomal ABC transporters in the mouse. Our data will enable sequence analysis in X-ALD patients to determine a possible role of ALDRP as a modifier and provide tools for the study of therapeutic ALDRP induction.

ATP Binding Cassette Transporter, Subfamily D↗

PubMed2007

Analysis of gene function in rice through virus-induced gene silencing.

Virus-induced gene silencing (VIGS) is a powerful RNA-silencing based technology adapted for the study of host-gene function. VIGS functions through the expression of a host gene from a virus vector. Both the virus-encoded host sequence and the homologous host target messenger RNA are destroyed or made inactive through a host surveillance system. Here, we describe procedures for the use of a new virus vector for VIGS in monocotyledonous hosts and, in particular, in rice (Oryza sativa), a species for which no VIGS vector was previously available.

Bromovirus↗

PubMed1995

The Polycomb and trithorax group proteins of Drosophila: trans-regulators of homeotic gene function.

The Polycomb and trithorax group genes encode trans-regulators of homeotic gene function in Drosophila. The Polycomb group genes encode transcriptional repressors, while the trithorax group proteins are positive factors required for homeotic gene function. Among the Polycomb group proteins, the POLYCOMB protein has been most extensively characterized. The POLYCOMB protein contains a chromodomain, a conserved domain found in a Drosophila protein with effects on position-effect variegation. Among the trithorax group proteins characterized, the BRAHMA protein appears to be a subunit of a protein complex conserved from yeast to man (the SNF/SWI complex) that modifies chromatin to facilitate the transcriptional activation by gene-specific DNA-binding proteins. The ZESTE protein may help to activate transcription by bringing distant cis-regulatory elements closer to promoter-bound proteins.

Animals↗

PubMed2000

Gene function.

The problem of gene function--of the relationships between hereditary material and the characteristics of organisms--preceded the rediscovery of Mendel's laws and accompanied the development of genetics in the XXth century. Molecular biologists replaced the simple gene-character relationship by two relationships: the first, between genes and proteins, was well defined, whereas the second between proteins and the complex structural and functional characteristics of organisms remained unknown. I will describe in this article the experimental approaches which helped to characterize during the last twenty years the relationships between proteins and characters. Four principles of macromolecular organization emerged from these studies: conservation of the elementary components during evolution, existence of pathways and networks, pleiotropy and redundancy. These principles are the explanation of the surprising experimental observations that have been made in recent years. The existence of these principles makes problematic any prediction on the consequences of gene modification. It both sounds the death-knell of the simplistic reductionist approach of many biologists, whereby genes were considered as responsible for specific functions, and definitely prevents the distribution of genes in separate, well defined categories.

Animals↗

PubMed1993

Evolution of the glutamine synthetase gene, one of the oldest existing and functioning genes.

We performed molecular phylogenetic analyses of glutamine synthetase (GS) genes in order to investigate their evolutionary history. The analyses were done on 30 DNA sequences of the GS gene which included both prokaryotes and eukaryotes. Two types of GS genes are known at present: the GSI gene found so far only in prokaryotes and the GSII gene found in both prokaryotes and eukaryotes. Our study has shown that the two types of GS gene were produced by a gene duplication which preceded, perhaps by > 1000 million years, the divergence of eukaryotes and prokaryotes. The results are consistent with the facts that (i) GS is a key enzyme of nitrogen metabolism found in all extant life forms and (ii) the oldest biological fossils date back 3800 million years. Thus, we suggest that GS genes are one of the oldest existing and functioning genes in the history of gene evolution and that GSI genes should also exist in eukaryotes. Furthermore, our study may stimulate investigation on the evolution of "preprokaryotes," by which we mean the organisms that existed during the era between the origin of life and the divergence of prokaryotes and eukaryotes.

Animals↗

PubMed2000

An efficient method for dispersing Ds elements in the barley genome as a tool for determining gene function.

To devise a method for function-based gene isolation and characterization in barley, we created a plasmid containing the maize Activator (Ac) transposase (AcTPase) gene and a negative selection gene, codA, and a plasmid containing Dissociation (Ds) inverted-repeat ends surrounding the selectable herbicide resistance gene, bar. These plasmids were used to stably transform barley (Hordeum vulgare). In vitro assays, utilizing a Ds-interrupted uidA reporter gene, were used to demonstrate high-frequency excisions of Ds when the uidA construct was introduced transiently into stably transformed, AcTPase-expressing plant tissue. Crosses were made between stably transformed plants expressing functional transposase under the transcriptional control of either the putative AcTPase promoter or the promoter and first intron from the maize ubiquitin (Ubi1) gene, and plants containing Ds-Ubi-bar. In F(1) plants from these crosses, low somatic and germinal transposition frequencies were observed; however, in F(2) progeny derived from individual selfed F(1) plants, up to 47% of the plants showed evidence of Ds transposition. Further analyses of F(3) plants showed that approximately 75% of the transposed Ds elements reinserted into linked locations and 25% into unlinked locations. Transposed Ds elements in plants lacking the AcTPase transposase gene could be reactivated by reintroducing the transposase gene through classical genetic crossing, making this system functional for targeted gene tagging and studies of gene function. During the analysis of F(3) plants we observed two mutant phenotypes in which the transposed Ds elements co-segregate with the new phenotype, suggesting the additional utility of such a system for tagging genes.

Chromosome Segregation↗

PubMed2003

Predicting gene function from patterns of annotation.

The Gene Ontology (GO) Consortium has produced a controlled vocabulary for annotation of gene function that is used in many organism-specific gene annotation databases. This allows the prediction of gene function based on patterns of annotation. For example, if annotations for two attributes tend to occur together in a database, then a gene holding one attribute is likely to hold the other as well. We modeled the relationships among GO attributes with decision trees and Bayesian networks, using the annotations in the Saccharomyces Genome Database (SGD) and in FlyBase as training data. We tested the models using cross-validation, and we manually assessed 100 gene-attribute associations that were predicted by the models but that were not present in the SGD or FlyBase databases. Of the 100 manually assessed associations, 41 were judged to be true, and another 42 were judged to be plausible.

Animals↗

PubMed2003

Strong associations between gene function and codon usage.

The association between codon usage and gene function was analyzed in the complete genomes of Eschericia coli, Bacillus subtilis, Lactococcus lactis and Campylobacter jejuni, using the functional annotation provided by NCBI. Two distinctly different ways of quantifying codon usage were used in the analysis. By using contingency tables it was found that for most amino acids a highly significant association with gene function exists for all species, indicating that codon usage at the level of individual amino acids is generally closely coordinated with gene function. By computing the effective number of codons in the annotated genes and comparing the median values in groups of different gene functions it was shown for all species that codon bias gene by gene also differs.

Amino Acids↗

PubMed2006

The microRNA: overview of the RNA gene that modulates gene functions.

MicroRNAs (miRNAs), widely distributed, small regulatory RNA genes, target both messenger RNA (mRNA) degradation and suppression of protein translation based on sequence complementarity between the miRNA and its targeted mRNA. Different names have been used to describe various types of miRNA. During evolution, RNA retroviruses or transgenes invaded the eukaryotic genome and inserted itself in the noncoding regions of DNA, conceivably acting as transposon-like jumping genes, providing defense from viral invasion and fine-tuning of gene expression as a secondary level of gene modulation in eukaryotes. When a transposon is inserted in the intron, it becomes an intronic miRNA, taking advantage of the protein synthesis machinery, i.e., mRNA transcription and splicing, as a means for processing and maturation. Recently, miRNAs have been found to play an important, but not life-threatening, role in embryonic development. They might play a pivotal role in diverse biological systems in various organisms, facilitating a quick response and accurate plotting of body physiology and structures. Based on these unique properties, manufactured intronic miRNAs have been developed for in vitro evaluation of gene function, in vivo gene therapy, and generation of transgenic animal models. The biogenesis and identification of miRNAs, potential applications, and future directions for research are presented in this chapter, hopefully providing a guideline for further miRNA and gene function studies.

Animals↗

PubMed2006

[Soil microbial ecological process and microbial functional gene diversity].

Soil microbes in terrestrial ecosystem carry out a series of important ecological functions, such as geo-chemical cycling of elements, degradation of pollutants, and buffering to the acute changes of environment, etc. Soil microbial ecological function has a close relation with soil function, and the changes in the structure and composition of soil microbial populations can directly affect the realization of soil function. Through their produced enzymes, soil microbes take part in a series of metabolic activities, and the functional genes of coded enzymes are the functional markers of microbes. In recent ten years, molecular ecology focusing on the functional gene diversity has been developed rapidly, which gives us a new cut-in point to understand soil microbial ecological function from the point of functional gene. This paper reviewed the research advances in the functional gene diversity correlated to soil microbial ecological function, with the perspectives in this field discussed.

Bacteria↗

PubMed1992

Use of gene replacement transformation to elucidate gene function in the qa gene cluster of Neurospora crassa.

Gene replacement by transformation, employing selective genetic recombination techniques, has been used to delete or disrupt the qa-x, qa-y and qa-1S genes of the qa gene cluster of Neurospora crassa. The growth characteristics of the strain carrying the deletion of the qa-y gene support earlier evidence that this gene encodes a quinic acid permease. The strain containing the deletion of the qa-1S gene (delta qa-1S) was examined with respect to quinic acid induction and carbon catabolite repression. The delta qa-1S strain exhibits constitutive expression of the qa genes supporting earlier evidence that the qa-1S gene codes for a repressor. Several of the qa genes continued to be expressed at high levels even in the presence of glucose in the delta qa-1S strain, which indicates that transcription of these genes is not being affected directly by a repressor molecule in the presence of glucose.

Chromosome Deletion↗

PubMed2004

Enhancing and diminishing gene function in human embryonic stem cells.

It is widely recognized that gain- and loss-of-function approaches are essential for understanding the functions of specific genes, and such approaches would be particularly valuable in studies involving human embryonic stem (hES) cells. We describe a simple and efficient approach using lipofection to transfect hES cells, which enabled us to generate hES cell lines expressing naturally fluorescent green or red proteins without affecting cell pluripotency. We used these cell lines to establish a means of diminishing gene function using small interfering (si)RNAs, which were effective at knocking down gene expression in hES cells. We then demonstrated that stable expression of siRNA could knock down the expression of endogenous genes. Application of these gain- and loss-of-function approaches should have widespread use, not only in revealing the developmental roles of specific human genes, but also for their utility in modulating differentiation.

Cell Culture Techniques↗