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At least 973 records · Page 54Linked to original sources
PubMed1996

The human cytomegalovirus UL94 open reading frame encodes a conserved herpesvirus capsid/tegument-associated virion protein that is expressed with true late kinetics.

In this report, we provide a detailed characterization of the human cytomegalovirus (HCMV) UL94 gene product. Northern (RNA) blot analysis of infected cell RNA demonstrated that UL94 message was found only at late times of infection and was not synthesized in the presence of the viral DNA replication inhibitor ganciclovir. Expression of the UL94 open reading frame in vitro and in vivo yielded a protein with the predicted molecular mass of 36 kDa. A monoclonal antibody raised to a UL94-specific peptide reacted specifically with a 36-kDa protein in HCMV-infected fibroblasts. This protein was found only at late times of infection and was also present in purified HCMV virions. Fractionation of purified virions and HCMV-infected cells revealed an association of UL94 immunoreactivity with the capsid/tegument and nuclear fractions, respectively. The evolutionary conservation of UL94 protein sequence and an analysis of potential functional regions of the protein are discussed.

Amino Acid Sequence↗
PubMed2005

Characterization of adrenomedullin in birds.

Adrenomedullin (AM) is a multifunctional evolutionarily highly conserved peptide. Although its genomic and amino acid (aa) sequences are known in several mammalian species and in fish, the structure of the AM gene remains unknown in intermediate phyla, including birds. Here, we report the structure and aa sequence of the chicken (c) AM ortholog. The cAM gene is located at the short arm of chromosome 5, which shows high synteny with the short arm of human (h) chromosome 11, where hAM is located. Key sequences in the third intron have been conserved which allow for an alternative splicing mechanism, similar to the one found in mammals. The preprohormone contains two peptides with high homology to human proadrenomedullin N-terminal 20 peptide (PAMP) and hAM. We found through real-time PCR and immunocytochemistry cAM mRNA and peptide expression in a variety of chicken tissues, which parallel patterns observed for mammals, with the exception that cAM levels are almost non-detectable in brain. Similarly to mammals, cAM expression is upregulated under hypoxic conditions and following dexamethasone treatment. These data demonstrate a high degree of homology between the cAM gene and its mammalian ortholog and evolutionary conservation of the regulatory mechanisms controlling its expression.

Adrenomedullin↗
PubMed2003

Computationally identifying novel NF-kappa B-regulated immune genes in the human genome.

Identifying novel NF-kappa B-regulated immune genes in the human genome is important to our understanding of immune mechanisms and immune diseases. We fit logistic regression models to the promoters of 62 known NF-kappa B-regulated immune genes, to find patterns of transcription factor binding in the promoters of genes with known immune function. Using these patterns, we scanned the promoters of additional genes to find matches to the patterns, selected those with NF-kappa B binding sites conserved in the mouse or fly, and then confirmed them as NF-kappa B-regulated immune genes based on expression data. Among 6440 previously identified promoters in the human genome, we found 28 predicted immune gene promoters, 19 of which regulate genes with known function, allowing us to calculate specificity of 93%-100% for the method. We calculated sensitivity of 42% when searching the 62 known immune gene promoters. We found nine novel NF-kappa B-regulated immune genes which are consistent with available SAGE data. Our method of predicting gene function, based on characteristic patterns of transcription factor binding, evolutionary conservation, and expression studies, would be applicable to finding genes with other functions.

Animals↗
PubMed1997

Mutation of a highly conserved residue of betaI spectrin associated with fatal and near-fatal neonatal hemolytic anemia.

We studied an infant with severe nonimmune hemolytic anemia and hydrops fetalis at birth. His neonatal course was marked by ongoing hemolysis of undetermined etiology requiring repeated erythrocyte transfusions. He has remained transfusion-dependent for more than 2 yr. A previous sibling born with hemolytic anemia and hydrops fetalis died on the second day of life. Peripheral blood smears from the parents revealed rare elliptocytes. Examination of their erythrocyte membranes revealed abnormal mechanical stability as well as structural and functional abnormalities in spectrin. Genetic studies revealed that the proband and his deceased sister were homozygous for a mutation of betaIsigma1 spectrin, L2025R, in a region of spectrin that is critical for normal function. The importance of leucine in this position of the proposed triple helical model of spectrin repeats is highlighted by its evolutionary conservation in all beta spectrins from Drosophila to humans. Molecular modeling demonstrated the disruption of hydrophobic interactions in the interior of the triple helix critical for spectrin function caused by the replacement of the hydrophobic, uncharged leucine by a hydrophilic, positively charged arginine. This mutation must also be expressed in the betaIsigma2 spectrin found in muscle, yet pathologic and immunohistochemical examination of skeletal muscle from the deceased sibling was unremarkable.

Anemia, Hemolytic, Congenital↗
PubMed1977

Three linked enzyme loci in fishes: implications in the evolution of vertebrate chromosomes.

A three-point linkage group comprised of loci coding for adenosine deaminase (ADA), glucose-6-phosphate dehydrogenase (G6PDH), and 6-phospho-gluconate dehydrogenase (6PGD) is described in fish of the genus Xiphophorus (Poeciliidae). The alleles at loci in this group were shown to assort independently from the alleles at three other loci--isocitrate dehydrogenase 1 and 2, and glyceraldehyde-3-phosphate dehydrogenase 1. Alleles at the latter three loci also assort independently from each other. Data were obtained by observing the segregation of electrophoretically variant alleles in reciprocal backcross hybrids derived from crosses between either X. helleri guentheri or X. h. strigatus and X. maculatus. The linkage component of chi2 was significant (less than 0.01) in all crosses, indicating that the linkage group is conserved in all populations of both species of Xiphophorus examined. While data from X. h. guentheri backcrosses indicate the linkage relationship ADA--6%--G6PDH--24%--6PGD, and ADA--29%--6PGD (30% when corrected for double crossovers), data from backcrosses involving strigatus, while supporting the same gene order, yielded significantly different recombination frequencies. The likelihood of the difference being due to an inversion could not be separated from the possibility of a sex effect on recombination in the present data. The linkage of 6PGD and G6PDH has been shown to exist in species of at least three classes of vertebrates, indicating the possibility of evolutionary conservation of this linkage.

Adenosine Deaminase↗
PubMed1999

Tlk, a novel evolutionarily conserved murine serine threonine kinase, encodes multiple testis transcripts.

Hypothesizing that genes important in meiotic processes in mammals might have evolutionarily conserved counterparts in lower organisms, we used the yeast IME2 meiotic gene (serine threonine kinase) as a probe for screening a mouse testis cDNA library. This screening resulted in identification of a novel putative serine threonine kinase. Although it did not exhibit significant homology to IME2, it did show significant sequence homology to the Tousled kinase in Arabidopsis. Tousled is associated with various differentiative processes including differentiation of the reproductive organs. The new murine gene was designated accordingly Tlk (Tousled like kinase). Tousled like kinase sequences have been reported to occur in C. elegans and in the human. Positive hybridization signals obtained in zooblot analysis suggest evolutionary conservation of Tlk throughout the phylogenetic ladder. Four distinct Tlk transcripts were detected in mouse testis, at least one of which is testis-specific. Northern and in situ hybridization analyses revealed that in normal testis, Tlk is expressed predominantly in pachytene spermatocytes and in round spermatids. Transcripts differ from one another in their 3' untranslated region, resulting from use of different polyadenylation sites, and in the length of their 5' region. Within the coding region, three of the putative peptides share the kinase and C-terminal domains but differ in their N-terminal domain, suggesting that the latter may be involved in the regulation of Tlk's function. We conclude that although Tlk might have an essential role in all tissues, these kinases are likely to take part in the complex array of phosphorylations involved in regulating spermatogenesis.

Aging↗
PubMed1995

The extra sex combs protein is highly conserved between Drosophila virilis and Drosophila melanogaster.

Extra sex combs (esc) is one of the Polycomb Group genes, whose products are required for long term maintenance of the spatially restricted domains of homeotic gene expression initially established by the products of the segmentation genes. We recently showed that the esc protein contains five copies of the WD motif, which in other proteins has been directly implicated in protein-protein interactions. Mutations affecting the WD repeats of the esc protein indicate that they are essential for its function as a repressor of the homeotic genes. We proposed that they may mediate interactions between esc and other Polycomb Group proteins, recruiting them to their target genes, perhaps by additional interactions with transiently expressed repressors such as hunchback. To further investigate the functional importance of the WD motifs and identify other functionally important regions of the esc protein, we have begun to determine its evolutionary conservation by characterizing the esc gene from Drosophila virilis, a distantly related Drosophila species. We show that the esc protein is highly conserved between these species, particularly its WD motifs. Their high degree of conservation, particularly at positions which are not conserved in the WD consensus derived from alignment of all known WD motifs, suggests that each of the WD repeats in the esc protein is functionally specialized and that this specialization has been highly conserved during evolution. Its highly charged N-terminus exhibits the greatest divergence, but even these differences are conservative of its predicted physical properties. These observations suggest that the esc protein is functionally compact, nearly every residue making an important contribution to its function.

Amino Acid Sequence↗
PubMed2000

A conserved nuclear receptor consensus sequence (DR-4) mediates transcriptional activation of the chicken CYP2H1 gene by phenobarbital in a hepatoma cell line.

Phenobarbital-responsive DNA elements were identified in the 5'-flanking region of the chicken CYP2H1 gene by in reporter gene assays in a chicken hepatoma cell line (leghorn male hepatoma (LMH)). A 264-base pair (bp) enhancer sequence (phenobarbital-responsive unit (PBRU)) responded to phenobarbital and a variety of phenobarbital-type inducers. Analysis of putative transcription factor binding sites within the 264-bp element revealed a nuclear receptor half-site repeat (DR-4) neighboring a putative nuclear factor-1 site. This motif resembles phenobarbital response elements in the flanking regions of three phenobarbital-inducible genes, rat CYP2B2, mouse Cyp2b10, and human CYP2B6. Activation of the 264-bp element was eliminated after site-directed mutagenesis of the DR-4 hexamer half-sites. Evidence for evolutionary conservation of this recognition site was indicated by activation in LMH cells of a mouse Cyp2b10 phenobarbital-responsive enhancer by the same spectrum of inducers that activate the CYP2H1 264-bp PBRU. Inhibition of this activation by okadaic acid may explain the reported inhibitory effects on induction of CYP2B1/2 and Cyp2b10 by this phosphatase inhibitor. We show that this inhibition occurs directly on the 264-bp PBRU, whereas the proximal promoter of CYP2H1 is induced by okadaic acid in reporter gene assays. These experiments exploit the unique phenobarbital inducibility of the hepatoma-derived cell line LMH.

Animals↗
PubMed2004

The oyster vasa-like gene: a specific marker of the germline in Crassostrea gigas.

The vasa gene is a key determinant for germline formation in eukaryotes. This gene, highly conserved through evolution, encodes a RNA helicase protein member of the DEAD-box family. To understand the germline formation in oyster, we report here the isolation and the characterization of a vasa orthologue in Crassostrea gigas (Oyvlg). OyVLG contained the eight consensus domains of the DEAD-box including those providing RNA unwinding activity. The expression pattern of Oyvlg was examined in adult oyster tissues at different reproductive stages. Its expression was restricted to germline cells both in males and females, including germinal stem cells and auxiliary cells. The expression of Oyvlg, strongest in early germ cells, decreased as the maturation proceeded. These data and the evolutionary conservation observed suggested the role of Oyvlg in germline development. Oyvlg is the first germ cell specific marker in oyster and will be very useful in studies of oyster germline formation.

Amino Acid Sequence↗
PubMed2002

Comparative genomic analysis of equilibrative nucleoside transporters suggests conserved protein structure despite limited sequence identity.

Equilibrative nucleoside transporters (ENTs) are a recently characterized and poorly understood group of membrane proteins that are important in the uptake of endogenous nucleosides required for nucleic acid and nucleoside triphosphate synthesis. Despite their central importance in cellular metabolism and nucleoside analog chemotherapy, no human ENT gene has been described and nothing is known about gene structure and function. To gain insight into the ENT gene family, we used experimental and in silico comparative genomic approaches to identify ENT genes in three evolutionarily diverse organisms with completely (or almost completely) sequenced genomes, Homo sapiens, Caenorhabditis elegans and Drosophila melanogaster. We describe the chromosomal location, the predicted ENT gene structure and putative structural topologies of predicted ENT proteins derived from the open reading frames. Despite variations in genomic layout and limited ortholog protein sequence identity (< or =27.45%), predicted topologies of ENT proteins are strikingly similar, suggesting an evolutionary conservation of a prototypic structure. In addition, a similar distribution of protein domains on exons is apparent in all three taxa. These data demonstrate that comparative sequence analyses should be combined with other approaches (such as genomic and proteomic analyses) to fully understand structure, function and evolution of protein families.

Alternative Splicing↗
PubMed1986

Sequences from sea urchin TU transposons are conserved among multiple eucaryotic species, including humans.

Sequences homologous to various structural domains of the Strongylocentrotus purpuratus TU family of transposons are present in sea urchin species closely related to S. purpuratus and were found in close proximity to each other in linkage patterns that differed for different species. Sequence homologs of the inverted repeat outer domain (IVR-OD) segment were, in addition, present in a sea urchin related only distantly to S. purpuratus and in all other eucaryotic organisms surveyed. In humans, a polymorphic hybridization pattern was seen for genomic DNA obtained from different individuals. Sequence comparisons revealed that repeated sequence motifs similar to those making up the 15-base-pair direct repeat unit of the IVR-OD domain of the TU elements exist in the IVRs of transposons identified in Drosophila melanogaster and maize and in the transcription control regions of certain eucaryotic viral and cellular genes. The remarkable evolutionary conservation of IVR-OD homologs may reflect a biological role for these sequences in DNA transposition, the regulation of gene expression, or both.

Animals↗
PubMed1992

Nuclear transport and nuclear pores in yeast.

The central features of nuclear import have been conserved during evolution. In yeast the nuclear accumulation of proteins follows the same selective and active transport mechanisms known from higher eukaryotes. Yeast nuclear proteins contain nuclear localization sequences (NLS) which are presumably recognized by receptors in the cytoplasm and the nuclear envelope. Subsequent to this recognition step, nuclear proteins are translocated into the nucleus via the nuclear pore complexes. The structure of the yeast nuclear pore complex resembles that of higher eukaryotes. Recently, the first putative components of the yeast nuclear import machinery have been cloned and sequenced. The genetically amenable yeast system allows for an efficient structural and functional analysis of these components. Due to the evolutionary conservation potential insights into the nuclear import mechanisms in yeast can be transferred to higher eukaryotes. Thus, yeast can be considered as a eukaryotic model system to study nuclear transport.

Biological Evolution↗
PubMed1980

Sex chromosome associated satellite DNA: evolution and conservation.

Satellites visible in female but not in male DNA were isolated from the snakes Elaphe radiata (satellite IV, p = 1.708 g x cm-3) and Bungarus fasciatus (BK1 minor, p = 1.709 g x cm-3). The satellites cross hybridize. Hybridization of 3H labelled nick translated BK minor satellite DNA with the total male and female DNA and/or chromosomes in situ of different species of snakes revealed that its sequences are conserved throughout the snake group and are mainly concentrated on the W chromosomes. Snakes lacking sex chromosomes do possess related sequences but there is no sex difference and visible related satellites are absent. The following conclusions have been reached on the basis of these results. 1. The W chromosome associated satellite DNA is related to similar sequences scattered in the genome. 2. The origin and increment in the number of the W satellite DNA sequence on the W chromosome is assoicated with the heterochromatinization of the W. 3. Satellite sequences have become distributed along the length of the W and resulted in morphological differentiation of sex chromosomes. 4. Evolutionary conservation of W satellite DNA strongly suggests that functional constraints may have limited sequence divergence.

Animals↗
PubMed1989

A conserved 3'----5' exonuclease active site in prokaryotic and eukaryotic DNA polymerases.

The 3'----5' exonuclease active site of E. coli DNA polymerase I is predicted to be conserved for both prokaryotic and eukaryotic DNA polymerases based on amino acid sequence homology. Three amino acid regions containing the critical residues in the E. coli DNA polymerase I involved in metal binding, single-stranded DNA binding, and catalysis of the exonuclease reaction are located in the amino-terminal half and in the same linear arrangement in several prokaryotic and eukaryotic DNA polymerases. Site-directed mutagenesis at the predicted exonuclease active site of the phi 29 DNA polymerase, a model enzyme for prokaryotic and eukaryotic alpha-like DNA polymerases, specifically inactivated the 3'----5' exonuclease activity of the enzyme. These results reflect a high evolutionary conservation of this catalytic domain. Based on structural and functional data, a modular organization of enzymatic activities in prokaryotic and eukaryotic DNA polymerases is also proposed.

Amino Acid Sequence↗
PubMed1997

The prohibitin family of mitochondrial proteins regulate replicative lifespan.

Cellular senescence is determined by multiple factors, including the genetic regulation of metabolism and responses to endogenous and exogenous stresses [1-4]. Recent studies implicate a limited number of gene products in elongating lifespan in yeast and Caenorhabditis elegans [2-4]; these include the C, elegans gene cik-1, a central regulator of metabolism [5], and yeast RAS2, which controls the response to ultraviolet irradiation and other stresses [3]. Another gene postulated to effect senescence is PHB1, the yeast homologue of prohibitin [3], a rodent gene initially identified as a potential regulator of growth arrest and tumour suppressor [6-8]. Highly conserved prohibitin homologues have been identified in mammals [9], Drosophila [10], C. elegans [9], plants [11] and yeast. A second mammalian gene, encoding BAP37, a protein with sequence similarity to prohibitin, is thought to be involved in lymphocyte function [9]. Here, we show that the nuclear-encoded mammalian prohibitin and BAP37 proteins are present in mitochondria, are co-expressed, and interact physically with each other. Deletion of the Saccharomyces cerevisiae homologues, PHB1 and PHB2, results in a decreased replicative lifespan and a defect in mitochondrial membrane potential. Our observations highlight the relationship between the metabolic efficiency of cells and the ageing process, and provide evidence for its evolutionary conservation.

Amino Acid Sequence↗
PubMed2003

Structure and expression of goat GLYCAM1 gene: lactogenic-dependent expression in ruminant mammary gland and interspecies conservation of the proximal promoter.

A macroarray approach used to list genes differentially expressed in goat mammary gland (gestation vs. lactation), other than milk protein genes, allowed us to detect the Glycosylation-dependent Cell Adhesion Molecule 1 (GLYCAM1) gene. GLYCAM1, a member of the glycoprotein mucin family, is a component of the milk fat globule membrane (MFGM). Its complete cDNA and gene sequences were determined and it was mapped by fluorescent in situ hybridization (FISH) on goat and cattle chromosome 5 (CHI5q21 and BTA5q21), and on sheep chromosome 3 (OAR3q21). Northern blot analyses confirmed its differential expression during the development and differentiation of the mammary gland of ruminants with a significantly higher mRNA amount during lactation than during pregnancy. An experimental in vivo induction model for lactation, developed by Kann et al., showed that the expression of GLYCAM1 is hormonally regulated in the mammary gland of ewes. Interspecies comparison of the gene promoter revealed the evolutionary conservation of a short proximal nucleotide sequence encompassing several transcription factor binding sites that could mediate the above-mentioned hormonal regulation.

Animals↗
PubMed1984

Conservation in rat liver of light and heavy subunit sequences of mammalian ferritin. Presence of unique octopeptide in the light subunit.

Ferritin, an iron-storage protein found in all life forms examined, is composed of varying proportions of two subunits of different molecular weight, heavy (H) and light (L). Using cDNA clones, we have determined the nucleotide sequence corresponding to the mRNA of the L-subunit of rat liver ferritin. The coding region of 546 nucleotides (182 amino acids) is flanked by 5'- and 3' -untranslated regions of approximately 130 and 150 nucleotides, respectively. The rat liver L-subunit amino acid sequence derived from the reading frame of the cDNA showed 88% and 82% homology, respectively, with the amino acid sequences of horse spleen ferritin (Heusterspreute, M., and Crichton, R. R. (1981) FEBS Lett. 129, 322-327), and human spleen ferritin (Wustefeld, C., and Crichton, R. R. (1982) FEBS Lett. 150, 43-48), thus demonstrating evolutionary conservation of the L-subunit sequence. However, a major difference between the rat and the horse and human sequences is the insertion of an octopeptide near the COOH-terminus of the rat protein resulting in a slightly longer peptide chain in this species. The reading frame and parts of the derived amino acid sequence including the octopeptide sequence were confirmed by direct amino acid sequencing of cyanogen bromide peptides from rat liver ferritin. Minor fragments of rat liver ferritin, presumably derived from the H-subunit, were also isolated after cyanogen bromide treatment. On sequencing, these H-peptides showed limited homology with regions of the L-sequence but extensive homology with published H-sequences from human liver and spleen. The H-subunit sequence did not contain the octopeptide found as part of the L-subunit sequence.

Amino Acid Sequence↗
PubMed1993

[The evolutionarily conserved gene Nc70F, expressed in nerve tissue of Drosophila melanogaster, encodes a protein homologous to the mouse delta transcription factor].

A cDNA copy of the Nc70F gene which is specifically expressed in Drosophila neural tissue was cloned and characterized. The gene has an open reading frame for the protein of 384 amino acids. The protein contains dimerization, DNA binding, activation and repression domains which are common for the eucaryotic transcription factors. However, the domain organization of the Nc70F protein has some peculiarities. The primary structure of the Nc70F product and other transcription factors were compared. High level of homology of Nc70F protein with the mouse delta transcription factor was found. The in situ hybridization on tissue section showed that the Nc70F gene expression is restricted to the central nerve system at all stages of Drosophila ontogenesis. By using Drosophila genomic and cDNA clones of Nc70F genes as probes, homologous transcripts were identified in the human poly(A) +RNA. The evolutionary conservative portion of this gene was localized in the 5-exons.

Amino Acid Sequence↗