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At least 1,531 records · Page 85Linked to original sources
PubMed2005

Comparative analysis of protein coding sequences from human, mouse and the domesticated pig.

BACKGROUND: The availability of abundant sequence data from key model organisms has made large scale studies of molecular evolution an exciting possibility. Here we use full length cDNA alignments comprising more than 700,000 nucleotides from human, mouse, pig and the Japanese pufferfish Fugu rubrices in order to investigate 1) the relationships between three major lineages of mammals: rodents, artiodactyls and primates, and 2) the rate of evolution and the occurrence of positive Darwinian selection using codon based models of sequence evolution. RESULTS: We provide evidence that the evolutionary splits among primates, rodents and artiodactyls happened shortly after each other, with most gene trees favouring a topology with rodents as outgroup to primates and artiodactyls. Using an unrooted topology of the three mammalian species we show that since their diversification, the pig and mouse lineages have on average experienced 1.44 and 2.86 times as many synonymous substitutions as humans, respectively, whereas the rates of non-synonymous substitutions are more similar. The analysis shows the highest average dN/dS ratio in the human lineage, followed by the pig and then the mouse lineages. Using codon based models we detect signals of positive Darwinian selection in approximately 5.3%, 4.9% and 6.0% of the genes on the human, pig and mouse lineages respectively. Approximately 16.8% of all the genes studied here are not currently annotated as functional genes in humans. Our analyses indicate that a large fraction of these genes may have lost their function quite recently or may still be functional genes in some or all of the three mammalian species. CONCLUSIONS: We present a comparative analysis of protein coding genes from three major mammalian lineages. Our study demonstrates the usefulness of codon-based likelihood models in detecting selection and it illustrates the value of sequencing organisms at different phylogenetic distances for comparative studies.

Animals↗
PubMed1994

Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells.

Class I homeobox (Hox) genes encode a major group of transcription factors controlling embryonic development and have been implicated in the continuing process of hematopoietic cell differentiation. They are clustered on four chromosomes and, in early development, exhibit spatially restricted expression with respect to their 3'-->5' chromosomal position. By using an improved PCR-based method for amplifying total cDNA derived from limited cell numbers, we now describe the expression of class I Hox genes in highly purified CD34+ cell subpopulations isolated from normal human bone marrow that represent functionally distinct stem and progenitor cell compartments. Our data indicate that at least 16 different Hox genes, mainly from the A and the B clusters, are expressed in one or more of these subpopulations of human hematopoietic cells. Moreover, markedly elevated expression of some of the Hox genes found at the 3' end of the A and B clusters (e.g., HoxB3) was a unique feature of the subpopulations that contained the most primitive functionally defined cells, whereas genes located in the 5' region of each cluster (e.g., HoxA10) were found to be expressed at nearly equal levels in the CD34+ subpopulations analyzed. In contrast to the findings for CD34+ cells, expression of two selected Hox genes, HoxB3 and HoxA10, was virtually extinguished in the CD34- fraction of bone marrow cells. These results demonstrate the expression of a broad range of Hox genes in primitive hematopoietic cells and point to the existence of a regulated program of Hox gene expression during their normal development.

Antigens, CD↗
PubMed2004

Gene silencing using a heat-inducible RNAi system in Arabidopsis.

Controlling gene expression during plant development is an efficient tool to explore gene function. In this paper, we describe a gene expression system driven by a heat-shock gene promoter (HSP18.2), to trigger the expression of an intron-containing inverted-repeat. RNA interference became a powerful way for gene functional analysis by reverse genetic approaches. However, constitutive gene silencing cannot be used with genes involved in fundamental processes such as embryo viability. Inducible promoters provide an alternative approach for temporal and spatial gene expression control and we described here a new system, complementary to those using chemical gene inducers. To evaluate the efficiency of this system, RNA corresponding to the phytoene desaturase gene of Arabidopsis thaliana was used as a reporter gene in transgenic plants and a comparative study was performed using either the CaMV35S constitutive promoter or the HSP18.2 inducible promoter.

Arabidopsis↗
PubMed2004

Nonneutral evolution of the transcribed pseudogene Makorin1-p1 in mice.

Pseudogenes are nonfunctional relics of formerly functional genes and are thought to evolve neutrally. In some pseudogenes, however, the molecular evolutionary patterns are atypical of neutrally evolving sequences, exhibiting sequence conservation, codon-usage bias, and other features associated with functional genes. Makorin1-p1 is a transcribed pseudogene first identified in the mouse Mus musculus. The transcript of Makorin1-p1 can regulate the stability of the transcript of its paralogous functional gene Makorin1. Specifically, the half-life of Makorin1 mRNA increases significantly in the presence of Makorin1-p1 transcript, and targeted deletion of Makorin1-p1 is lethal in mice. Here, we show that Makorin1-p1 originated after the separation of Mus and Rattus but before the divergence of M. musculus and M. pahari. The transcribed region of Makorin1-p1 exhibits rates of point and indel substitutions that are two to four times lower than those in the untranscribed region, suggesting that the transcribed region is under functional constraint and is not evolving neutrally. Although the transcript of Makorin1-p1 likely functions by its sequence similarity to Makorin1, we find no evidence of gene conversion between them, indicating that functional conservation alone is sufficient to maintain their coordinated evolution. A duplication-degeneration model is proposed to explain how Makorin1-p1 was co-opted into the regulatory system of Makorin1. There are over 10,000 pseudogenes in a typical mammalian genome, and it is plausible that many functional but untranslatable pseudogenes exist. Our results illustrate the potential of using evolutionary analysis to identify such pseudogenes from genome sequences.

Animals↗
PubMed2004

Identification of differentially expressed genes in anagen dermal papilla by suppression subtractive hybridization.

BACKGROUND: We constructed a cDNA subtractive library of dermal papilla cells (DPCs) in anagen with suppression subtractive hybridization (SSH) technique and clone differentially expressed genes related to DPCs in anagen. METHODS: Total mRNA was isolated from DPCs of anagen and telogen follicles. Moreover, single-strand (ss) and double-strand (ds) cDNAs were synthesized in turn using SMART PCR cDNA synthesis technology. ds cDNAs then were digested with Rsa I and divided into two groups, and ligated to the specific adaptor 1 and adaptor 2R, respectively. After cDNAs were hybridized with each other twice and underwent two rounds of nested PCR. PCR products were ligated with arms of T/A plasmid vectors to set up the subtractive library. Selected clones were demonstrated by reverse Northern blot and sequenced. The acquired sequence data were aligned against the Genbank nucleotide database. RESULTS: cDNA subtractive library of DPCs in anagen follicles was set up successfully with high subtractive efficiency. Thirty-five genes were identified in this study with 22 known functional genes and 13 unknown functional genes. CONCLUSIONS: All results confirm the effectiveness and sensitivity of SSH in detecting differentially expressed genes from a small amount of clinical samples. Information about such alterations in gene expression could be useful for elucidating the genetic events in hair follicle growth regulation.

Adult↗
PubMed1996

Candida albicans homologue of GGP1/GAS1 gene is functional in Saccharomyces cerevisiae and contains the determinants for glycosylphosphatidylinositol attachment.

The GGP1/GAS1/CWH52 gene of Saccharomyces cerevisiae encodes a major exocellular 115 kDa glycoprotein (gp115) anchored to the plasma membrane through a glycosylphosphatidylinositol (GPI). The function of gp115 is still unknown but the analysis of null mutants suggests a possible role in the control of morphogenesis. PHR1 gene isolated from Candida alibicans is homologous to the GGP1 gene. In this report we have analysed the ability of PHR1 to complement a ggp1 delta mutation in S. cerevisiae. The expression of PHR1 controlled by its natural promoter or by the GGP1 promoter has been studied. In both cases we have observed a complete complementation of the mutant phenotype. Moreover, immunological analysis has revealed that PHR1 in budding yeast gives rise to a 75-80 kDa protein anchored to the membrane through a GPI, indicating that the signal for GPI attachment present in the C. albicans gene product is functional in S. cerevisiae.

Base Sequence↗
PubMed2006

A framework of integrating gene relations from heterogeneous data sources: an experiment on Arabidopsis thaliana.

One of the most important goals of biological investigation is to uncover gene functional relations. In this study we propose a framework for extraction and integration of gene functional relations from diverse biological data sources, including gene expression data, biological literature and genomic sequence information. We introduce a two-layered Bayesian network approach to integrate relations from multiple sources into a genome-wide functional network. An experimental study was conducted on a test-bed of Arabidopsis thaliana. Evaluation of the integrated network demonstrated that relation integration could improve the reliability of relations by combining evidence from different data sources. Domain expert judgments on the gene functional clusters in the network confirmed the validity of our approach for relation integration and network inference.

Arabidopsis↗
PubMed1990

Pancreatic function and gene deletion F508 in cystic fibrosis.

In view of the possible relation between pancreatic function and cystic fibrosis (CF) gene mutations, a detailed study on Italian patients was performed. Seventy pancreatic insufficient and 48 pancreatic sufficient patients were included after very accurate characterisation of their pancreatic and digestive function, all performed in the same CF centre. The CF gene deletion F508 was tested to define the patients' genotypes. The results confirm that the mutation correlates with pancreatic insufficiency, and is recessive to other, as yet unreported, mutant alleles that determine pancreatic sufficiency. An indication that duodenal bicarbonate output is more severely reduced in the presence of deletion F508 is also presented. The data are discussed in relation to a hypothesis on the primary effects of CF gene deletion F508.

Adolescent↗
PubMed1998

The S. cerevisiae CLU1 and D. discoideum cluA genes are functional homologues that influence mitochondrial morphology and distribution.

The cluA gene, encoding a novel 150 kDa protein, was recently characterized in Dictyostelium discoideum; disruption of cluA impaired cytokinesis and caused mitochondria to cluster at the cell center. The genome of Saccharomyces cerevisiae contains an open reading frame (CLU1) that encodes a protein that is 27% identical, 50% similar, to this Dictyostelium protein. Deletion of CLU1 from S. cerevisiae did not affect cell viability, growth properties, sporulation efficiency, or frequency of occurrence of cells lacking functional mitochondria. However, in clu1Delta cells the mitochondrial reticulum, which is normally highly branched, was condensed to one side of the cell. Transformation of cluA- Dictyostelium mutants with the yeast CLU1 gene yielded amoebae that divided normally and had dispersed mitochondria. The mitochondria in cluA- Dictyostelium cells complemented with CLU1 were not as widely scattered as in cluA+ Dictyostelium cells, but formed loose clusters throughout the cytoplasm. These results indicate that the products of the CLU1 and cluA genes, in spite of their limited homology, are functional homologues.

Amino Acid Sequence↗
PubMed1995

Evolution of neuroblast identity: seven-up and prospero expression reveal homologous and divergent neuroblast fates in Drosophila and Schistocerca.

In the Drosophila CNS, early neuroblast formation and fate are controlled by the pair-rule class of segmentation genes. The distantly related Schistocerca (grasshopper) embryo has a similar arrangement of neuroblasts, despite lack of known pair-rule gene function. Does divergent pair-rule gene function lead to different neuroblast identities, or can different patterning mechanisms produce homologous neuroblasts? We use four molecular markers to compare Drosophila and Schistocerca neuroblast identity: seven-up, prospero, engrailed, and fushi-tarazu/Dax. In both insects some early-forming neuroblasts share key features of neuroblast identity (position, time of formation, and temporally accurate gene expression); thus, different patterning mechanisms can generate similar neuroblast fates. In contrast, several later-forming neuroblasts show species-specific differences in position and/or gene expression; these neuroblast identities seem to have diverged, suggesting that evolution of the insect central nervous system can occur through changes in embryonic neuroblast identity.

Amino Acid Sequence↗
PubMed1999

Identification of a functional fur gene in Bradyrhizobium japonicum.

The recent identification of the iron response regulator (Irr) in Bradyrhizobium japonicum raised the question of whether the global regulator Fur is present in that organism. A fur gene homolog was isolated by the functional complementation of an Escherichia coli fur mutant. The B. japonicum Fur bound to a Fur box DNA element in vitro, and a fur mutant grown in iron-replete medium was derepressed for iron uptake activity. Thus, B. japonicum expresses at least two regulators of iron metabolism.

Amino Acid Sequence↗
PubMed1999

Preservation of duplicate genes by complementary, degenerative mutations.

The origin of organismal complexity is generally thought to be tightly coupled to the evolution of new gene functions arising subsequent to gene duplication. Under the classical model for the evolution of duplicate genes, one member of the duplicated pair usually degenerates within a few million years by accumulating deleterious mutations, while the other duplicate retains the original function. This model further predicts that on rare occasions, one duplicate may acquire a new adaptive function, resulting in the preservation of both members of the pair, one with the new function and the other retaining the old. However, empirical data suggest that a much greater proportion of gene duplicates is preserved than predicted by the classical model. Here we present a new conceptual framework for understanding the evolution of duplicate genes that may help explain this conundrum. Focusing on the regulatory complexity of eukaryotic genes, we show how complementary degenerative mutations in different regulatory elements of duplicated genes can facilitate the preservation of both duplicates, thereby increasing long-term opportunities for the evolution of new gene functions. The duplication-degeneration-complementation (DDC) model predicts that (1) degenerative mutations in regulatory elements can increase rather than reduce the probability of duplicate gene preservation and (2) the usual mechanism of duplicate gene preservation is the partitioning of ancestral functions rather than the evolution of new functions. We present several examples (including analysis of a new engrailed gene in zebrafish) that appear to be consistent with the DDC model, and we suggest several analytical and experimental approaches for determining whether the complementary loss of gene subfunctions or the acquisition of novel functions are likely to be the primary mechanisms for the preservation of gene duplicates. For a newly duplicated paralog, survival depends on the outcome of the race between entropic decay and chance acquisition of an advantageous regulatory mutation. Sidow 1996(p. 717) On one hand, it may fix an advantageous allele giving it a slightly different, and selectable, function from its original copy. This initial fixation provides substantial protection against future fixation of null mutations, allowing additional mutations to accumulate that refine functional differentiation. Alternatively, a duplicate locus can instead first fix a null allele, becoming a pseudogene. Walsh 1995 (p. 426) Duplicated genes persist only if mutations create new and essential protein functions, an event that is predicted to occur rarely. Nadeau and Sankoff 1997 (p. 1259) Thus overall, with complex metazoans, the major mechanism for retention of ancient gene duplicates would appear to have been the acquisition of novel expression sites for developmental genes, with its accompanying opportunity for new gene roles underlying the progressive extension of development itself. Cooke et al. 1997 (p. 362)

Animals↗
PubMed1998

Assessment of cardiac function and gene expression at an early phase after myocardial infarction.

The purpose of this study was to examine left ventricular function and cardiac gene expressions at an acute phase after myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Two days after MI, we performed Doppler-echocardiography and measured the systolic and diastolic function. We then analyzed the contractile protein and extracellular matrix mRNAs of cardiac tissues in the infarcted region, including the adjacent noninfarcted myocardium (the adjacent noninfarcted myocardium) and the remote noninfarcted myocardium, by Northern blot hybridization. Fractional shortening decreased significantly to 28%. Peak early diastolic filling wave (E wave) velocity increased in MI rats (MI; 90 +/- 3 cm/s versus the control; 71 +/- 2 cm/s, p < 0.05), and the deceleration rate of the E wave velocity was more rapid in MI rats (MI; 22.0 +/- 2.6 m/s2 versus the control; 16.5 +/- 2.0 m/s2, p < 0.01). Atrial filling wave (A wave) velocity decreased, resulting in a marked increase in the ratio of E wave to A wave velocity (MI; 3.1 +/- 0.3 versus the control; 2.1 +/- 0.2, p < 0.01). In the adjacent noninfarcted myocardium, mRNA levels for alpha-skeletal actin, atrial natriuretic polypeptide (ANP), transforming growth factor-beta 1(TGF-beta 1), fibronectin, and collagen types I and III increased significantly. In the remote noninfarcted myocardium, mRNA levels for alpha-skeletal actin, ANP, and collagen types I and III increased, while mRNA levels for beta-myosin heavy chain, TGF-beta 1 and fibronectin did not change. We observed left ventricular dysfunction and different gene expression between adjacent noninfarcted myocardium and in the remote noninfarcted myocardium two days after MI. These findings suggest that cardiac gene expression after MI may be a compensation reaction for cardiac dysfunction induced by myocardial damage.

Animals↗
PubMed2002

Orf virus encodes a functional dUTPase gene.

The present study is the first report on the functional activity of a parapoxvirus-encoded dUTPase. The dUTPase gene of the attenuated orf virus (ORFV), strain D1701, was expressed as a bacterial thioredoxin fusion protein. In vitro assays showed that ORFV dUTPase was highly specific for dUTP as substrate. The enzyme was active over a broad pH range (pH 6.0-9.0), with maximal enzymatic activity at pH 7.0 in the presence of Mg(2+) cations. Kinetic studies of the recombinant ORFV dUTPase revealed an apparent K(m) of 4.0 microM, which is more similar to that of the mammalian or African swine fever virus enzyme than to the K(m) of vaccinia virus dUTPase. Enzyme activity was also found with purified ORFV particles, indicating its virion association.

Deoxyuracil Nucleotides↗
PubMed2002

[The research progress in the disease model of knock-out mouse].

The knock-out technology is an effective means in studying the gene function of organism. The disease model of gene knock-out mouse is of significance in understanding the gene function and pathogenesis of human disease. The available models of gene knock-out mouse are classified and summarized to promote the development of related research.

English Abstract↗
PubMed1998

Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function and gene expression in cultured airway parasympathetic neurons.

Viral infections increase vagally mediated reflex bronchoconstriction. Decreased function of inhibitory M2 muscarinic receptors on the parasympathetic nerve endings is likely to contribute to increased acetylcholine release. In this study, we used cultured airway parasympathetic neurons to determine the effects of parainfluenza virus and of interferon (IFN)-gamma on acetylcholine release, inhibitory M2 receptor function, and M2 receptor gene expression. In control cultures, electrically stimulated acetylcholine release increased when the inhibitory M2 receptors were blocked using atropine (10(-)5 M) and decreased when these receptors were stimulated using methacholine (10(-)5 M). Acetylcholine release was increased by viral infection and by treatment with IFN-gamma (300 U/ml). In these cells, atropine did not further potentiate, nor did methacholine inhibit, acetylcholine release, suggesting decreased inhibitory M2 receptor function and/or expression. Using a competitive reverse transcription-polymerase chain reaction method, we demonstrated that M2 receptor gene expression was decreased by more that an order of magnitude both by virus infection and by treatment with IFN. Thus, viral infections may increase vagally mediated bronchoconstriction both by directly inhibiting M2 receptor gene expression and by causing release of IFN-gamma which inhibits M2 receptor gene expression.

Acetylcholine↗
PubMed2001

Hypercholesterolemia alters vascular functions and gene expression of potassium channels in rat aortic smooth muscle cells.

AIM: To investigate the effects of hypercholesterolemia on functions of rat aorta and on gene expression of inward rectifier and ATP-sensitive potassium channels in aortic smooth muscle. METHODS: Rats were treated with high-cholesterol emulsion ig for 2 weeks; the aortic rings with and without endothelium were prepared to examine the aortic contractile and relaxation responses; RT-PCR was used to observe the gene expression of inward rectifier and ATP-sensitive potassium channels. RESULTS: Hypercholesterolemia damaged the endothelium-dependent vascular functions severely, but did not affect the endothelium-independent vascular functions; Kir6.2 mRNA expression was upregulated (P < 0.05) and Kir3.1 mRNA expression was downregulated markedly (P < 0.05) in hypercholesterolemic smooth muscle. CONCLUSION: Hypercholesterolemia altered the vascular functions and regulated gene expression levels of specific inward rectifier and ATP-sensitive potassium channel subtypes.

Animals↗
PubMed1991

The chloroplast gene for ribosomal protein CL23 is functional in tobacco.

Chloroplast rpl23 loci potentially coding for a polypeptide homologous to the E. coli L23 ribosomal protein are frame-shifted in spinach and several other plants, indicating that these loci are pseudogenes. In tobacco, rpl23 constitutes a continuous open reading frame of 93 codons and its transcript initiates at least 66 bp upstream from the initiation codon. The N-terminal amino acid sequence of a 13 kDa protein from the 50 S subunit of tobacco chloroplast ribosomes matches that derived from the tobacco rpl23 locus. This shows that rpl23 is a functional gene in tobacco.

Amino Acid Sequence↗