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At least 343 records · Page 19Linked to original sources
PubMed2001

Comparative analysis of the genomic organization of Pax9 and its conserved physical association with Nkx2-9 in the human, mouse, and pufferfish genomes.

As a first step towards the identification of cis-regulatory elements of Pax9 by means of comparative genomics, we have analyzed genome regions encompassing the Pax9 gene in three vertebrate species, humans, mice (Mus musculus), and the Japanese pufferfish (Fugu rubripes). We show the genomic organization of Pax9 and its physical association with Nkx2-9 conserved in the three species. We discuss about possible implications of the conserved synteny between Pax9 and Nkx2-9 in a context of vertebrate evolution. This report also includes the first description of the primary structures of Fugu Pax9 and Nkx2-9. Furthermore, we report the identification of a novel upstream exon and putative transcription start sites in mouse Pax9. Our results suggest that transcription of Pax9 may be initiated at two alternative start sites and driven by TATA-less promoters.

Amino Acid Sequence↗
PubMed2003

Characterization of hey bHLH genes in teleost fish.

Hairy-related basic helix-loop-helix (bHLH) transcription factors are targets of Delta-Notch signaling and represent essential components for a number of cell fate decisions during vertebrate embryogenesis. Hey genes encode a subfamily of hairy-related proteins that have been implicated in processes like somitogenesis, blood vessel and heart development. We have identified and characterized hey genes in three teleost fish lineages using degenerate PCR and database searches. Phylogenetic analysis of Hey proteins suggests a complex pattern of evolution with high divergence of hey2 in Takifugu rubripes (Fugu, Japanese pufferfish) and possibly loss in the related Tetraodon nigroviridis (the freshwater pufferfish). In addition, duplication of hey1 in both pufferfishes, Fugu and Tetraodon, was observed. Conversely, zebrafish (Danio rerio) has the same complement of three hey genes as known from mammals. All three hey genes show much more restricted gene expression profiles in zebrafish when compared to mouse. Importantly, while all three murine Hey genes are expressed in overlapping patterns in the presomitic mesoderm (PSM) and somites, in zebrafish only hey1 shows PSM and somite expression in a highly dynamic fashion. Therefore, while overlapping expression might account for redundancy of hey function in higher vertebrates, this is unlikely to be the case in zebrafish. In deltaD (dlD) deficient after-eight zebrafish mutants, the dynamic expression of hey1 in the PSM is impaired and completely lost in newly formed somitomeres. Overexpression of dlD on the other hand results in the ectopic expression of hey1 in the axial mesoderm. Hence, hey1 represents a target of Delta-Notch signaling dynamically expressed during somite formation in zebrafish.

Amino Acid Sequence↗
PubMed2004

Regulation of the MID1 protein function is fine-tuned by a complex pattern of alternative splicing.

Clinical features of Opitz BBB/G syndrome are confined to defects of the developing ventral midline, whereas the causative gene, MID1, is ubiquitously expressed. Therefore, a non-redundant physiological function of the MID1 product appears to be developmentally restricted. Here, we report the identification of several alternative MID1 exons in human, mouse and fugu. We show that splice variants of the MID1 gene that are comparable in terms of function occur in the three organisms, suggesting an important role in the regulation of the MID1 protein function. Accordingly, we observed differential MID1 transcript patterns in a tissue-specific manner by Northern blot and RT-PCR. The identified splice variants cause loss-of-function effects via several mechanisms. Some introduce a stop codon followed by a novel poly(A(+)) tail, leading to the formation of C-terminally truncated proteins. Dominant negative effects through altered binding to the MID1-interacting protein alpha4 in vitro could be demonstrated in a couple of cases. Others carry premature termination codons without poly(A(+)) tails. These are degraded by nonsense mediated mRNA decay (NMD). Our data reveal a mechanism conserved in human, mouse and fugu that regulates developmentally restricted MID1 activity and suggest NMD to be critical in the translational regulation of a ubiquitously transcribed mRNA.

Alternative Splicing↗
PubMed2005

Genetic basis of tetrodotoxin resistance in pufferfishes.

Tetrodotoxin (TTX) is a highly potent neurotoxin that selectively binds to the outer vestibule of voltage-gated sodium channels. Pufferfishes accumulate extremely high concentrations of TTX without any adverse effect. A nonaromatic amino acid (Asn) residue present in domain I of the pufferfish, Takifugu pardalis, Na v1.4 channel has been implicated in the TTX resistance of pufferfishes . However, the effect of this residue on TTX sensitivity has not been investigated, and it is not known if this residue is conserved in all pufferfishes. We have investigated the genetic basis of TTX resistance in pufferfishes by comparing the sodium channels from two pufferfishes (Takifugu rubripes [fugu] and Tetraodon nigroviridis) and the TTX-sensitive zebrafish. Although all three fishes contain duplicate copies of Na v1.4 channels (Na v1.4a and Na v1.4b), several substitutions were found in the TTX binding outer vestibule of the two pufferfish channels. Electrophysiological studies showed that the nonaromatic residue (Asn in fugu and Cys in Tetraodon) in domain I of Na v1.4a channels confers TTX resistance. The Glu-to-Asp mutation in domain II of Tetraodon channel Na v1.4b is similar to that in the saxitoxin- and TTX-resistant Na+ channels of softshell clams . Besides helping to deter predators, TTX resistance enables pufferfishes to selectively feed on TTX-bearing organisms.

Amino Acid Sequence↗
PubMed2004

The molecular evolution of the interleukin-1 family of cytokines; IL-18 in teleost fish.

The cytokine network is an important homeostatic system with potent activities in immune surveillance, growth, developmental and repair processes. Although interleukin-1beta (IL-1beta) is considered a pivotal pro-inflammatory cytokine, merely focussing on its inflammatory role would be too narrow an approach. Elucidation of the human, the mouse and the Fugu rubripes (pufferfish) genome now enables a more comprehensive overview of this cytokine family and its receptors in several vertebrate classes. Phylogenetic analyses of the IL-1 family members, comprising over 80 sequences of various fish, amphibian, avian and mammalian species, reveal that for only a few mammalian IL-1 family members unambiguous orthologues have been found in fish, indicating a recent origin of some of the mammalian IL-1 family members. Interestingly, the Fugu genome did reveal teleost orthologues for IL-18 and its putative receptor complex. All teleost IL-1beta sequences cluster separately from IL-1beta sequences of other species. In contrast, a number of IL-1 receptor family members have well conserved fish orthologues. This supports the concept of an ancestral role of this family, possibly in the brain.

Amino Acid Motifs↗
PubMed2005

Comparative genomics of the Hlx homeobox gene and protein: conservation of structure and expression from fish to mammals.

Hlx is a homeobox transcription factor gene that is expressed in intestinal and hepatic mesenchyme of the developing mouse embryo and is essential for normal intestinal and hepatic development. Because of the morphological and molecular similarities in the development of the digestive system across species, we hypothesized that the Hlx gene and protein sequences and expression patterns would be conserved among vertebrates. Comparison of the Hlx gene orthologues of human, chimpanzee, mouse, rat, pufferfish (Fugu) and zebrafish demonstrates that these six genes share an identical organization with four exons and three introns. Comparison of the inferred Hlx protein sequences from these and three additional species (chick, Spanish ribbed newt and rainbow trout) reveals significant sequence identity, with identical homeodomains. The expression of Hlx in the mesenchyme of developing chick embryos is highly similar to that of mouse. Fugu Hlx is expressed in a tissue-specific manner that is similar though not identical to that of mouse, suggesting a conservation of Hlx function between mammals and birds. The mammalian and fish Hlx genes share a putative 5' upstream enhancer as well as an inverted repeat containing CCAAT boxes on opposite strands that we have previously shown to be important for mouse Hlx gene expression. These results suggest that the function of Hlx and the mechanisms regulating its expression are highly conserved in mammals, birds, amphibians and fish.

Amino Acid Sequence↗
PubMed2005

Identification and analysis of teleost slow muscle troponin T (sTnT) and intronless TnT genes.

In the present study cDNA clones representing two slow skeletal muscle troponin T genes (sTnT1sb and sTnT2sb) in the sea bream (Sparus auratus), an important aquaculture species, were isolated and characterised. A third, intronless, TnT gene (iTnTsb), which is an apparent orthologue of a previously described zebrafish TnT, was also isolated. In adult sea bream sTnT expression was restricted to red muscle and, using northern blotting, a single low abundance transcript was identified for sTnT1sb (1260 nucleotides) and a single high abundance transcript was identified for sTnT2sb (1000 nucleotides). In contrast, iTnTsb is predominantly expressed in adult fast muscle. All three TnT genes are also expressed during larval development. Phylogenetic analysis of sea bream sTnT proteins to identify maximum parsimony showed that iTnTsb, sTnT1sb and sTnT2sb each cluster in independent groups. sTnT1sb clustered with other vertebrate sTnTs, while sTnT2 clustered with a group of fish specific sequences (from Fugu rubripes, Oryzia latipes and Salmo trutta). The teleost sTnT2 and iTnT each constitute new, apparently teleost specific, TnT groups. Analysis of the corresponding Fugu scaffold indicates that sTnT2sb is encoded by a gene with twelve exons. The two sTnT cDNAs isolated in sea bream probably arose by duplication of an ancestral gene, and iTnT by reverse transcription. It remains to be established if the encoded proteins have different structural and mechanistic roles in fish muscle.

Amino Acid Sequence↗
PubMed2006

Organization and structure of hox gene loci in medaka genome and comparison with those of pufferfish and zebrafish genomes.

We isolated BAC clones that cover the entire hox gene loci in the medaka fish Oryzias latipes. The BAC clones were characterized by the Southern hybridization with many hox gene probes isolated in our previous study and by PCR using primers designed for selective amplification of respective hox genes. Then, the BAC clones have been subjected to shotgun sequencing. The results revealed the organization of the entire hox gene loci. Forty-six hox genes in total are encoded in seven clusters as follows: 10 hox genes in Aa cluster; 5 in Ab; 9 in Ba; 4 in Bb; 10 in Ca; 6 in Da; and 2 in Db. Together with the information on the hox gene loci registered in the Fugu genome database and in the Danio genome database, the physical maps of three fish genomes were constructed and compared one another. Not only numbers of hox genes but also the distances between the neighboring hox genes are highly similar between medaka and fugu. As for six clusters, Aa, Ab, Ba, Bb, Ca and Da that are commonly present in the three fishes, only few or no differences were found in each cluster. Thus, the hox gene sets should have been well conserved once they had been established in respective species.

Animals↗
PubMed2005

Differential expression of tuberoinfundibular peptide 38 and glucose-6-phosphatase in tilapia.

A new parathyroid hormone (PTH)-like endocrine system has been identified in mammals and fishes consisting of the PTH type-2 receptor (PTH2R) and tuberoinfundibular peptide 39 (TIP39). Although the mammalian PTH2R-TIP39 system is involved in nociception and pituitary regulation, the function(s) of this system in fishes is undetermined. Using degenerate primers based on conserved zebrafish and fugu TIP39 nucleotide sequences, 3'-RACE reactions isolated the coding region of a putative TIP38 cDNA in the Nile tilapia (Oreochromis niloticus). Tilapia-specific primers were subsequently used in 5'-RACE reactions to isolate the remaining portion of the transcript. The cDNA encoding O. niloticus TIP (OnTIP38) was determined to yield a 38 amino acid secreted hormone. A second tilapia TIP38 cDNA was isolated from the euryhaline Mozambique tilapia (OmTIP38). Except for the 39th residue, both tilapia cDNA sequences showed significant identity to human, bovine, murine, fugu, and zebrafish TIP39. To determine the tissue-specific expression of OnTIP38 and OmTIP38, real-time quantitative RT-PCR (rQRT-PCR) was performed on skin, gill, kidney, testis, heart, and brain. In freshwater (FW)-acclimated Nile tilapia, OnTIP38 showed highest levels of expression in kidney and lowest levels in skin and gill. In Mozambique tilapia tissues, expression of OmTIP38 and G6Pase (glucose-6 phosphatase) were higher in salt water (SW)-acclimated fish than in FW-acclimated fish. G6Pase expression, and not OmTIP38, showed significant differences among various tissues in FW- and SW-acclimated fish. Results of the present study clearly indicate that the TIP38/39-PTH2R system shows considerable conservation in sequence identity and tissue-specific expression in mammals and fishes.

Adaptation, Physiological↗
PubMed2000

Comparative analysis of the DRADA A-to-I RNA editing gene from mammals, pufferfish and zebrafish.

The DRADA gene in mammals encodes an A-to-I RNA editase, an adenosine deaminase that acts on pre-mRNAs to produce site specific inosines. DRADA has been shown to deaminate specific adenosine residues in a subset of glutamate and serotonin receptors, and this editing results in proteins of altered sequences and functional properties. DRADA thus plays a role in creating protein diversity. To study the evolutionary significance of this gene, we have characterized the genomic structure of DRADA from Fugu rubripes, and compared the protein sequences of DRADA from mammals, pufferfish and zebrafish. The DRADA gene from Fugu is three-fold compacted with respect to the human gene, and contains a novel intron within the large second coding exon. DRADA cDNAs were isolated from zebrafish and a second pufferfish, Tetraodon fluviatilis. Comparisons among fish, and between fish and mammals, of the protein sequences show that the catalytic domains are highly conserved for each gene, while the RNA binding domains vary within a single protein in their levels of conservation. Conservation within the Z DNA binding domain has also been assessed. Different levels of conservation among domains of different functional roles may reflect differences in editase substrate specificity and/or substrate sequence conservation.

Adenosine Deaminase↗
PubMed2001

The human cDNA for a homologue of the plant enzyme 1-aminocyclopropane-1-carboxylate synthase encodes a protein lacking that activity.

The sequences of genes encoding homologues of 1-aminocyclopropane-1-carboxylate (ACC) synthase, the first enzyme in the two-step biosynthetic pathway of the important plant hormone ethylene, have recently been found in Fugu rubripes and Homo sapiens (Peixoto et al., Gene 246 (2000) 275). ACC synthase (ACS) catalyzes the formation of ACC from S-adenosyl-L-methionine. ACC is oxidized to ethylene in the second and final step of ethylene biosynthesis. Profound physiological questions would be raised if it could be demonstrated that ACC is formed in animals, because there is no known function for ethylene in these organisms. We describe the cloning of the putative human ACS (PHACS) cDNA that encodes a 501 amino acid protein that exhibits 58% sequence identity to the putative Fugu ACS and approximately 30% sequence identity to plant ACSs. Purified recombinant PHACS, expressed in Pichia pastoris, contains bound pyridoxal-5'-phosphate (PLP), but does not catalyze the synthesis of ACC. PHACS does, however, catalyze the deamination of L-vinylglycine, a known side-reaction of apple ACS. Bioinformatic analysis indicates that PHACS is a member of the alpha-family of PLP-dependent enzymes. Molecular modeling data illustrate that the conservation of residues between PHACS and the plant ACSs is dispersed throughout its structure and that two active site residues that are important for ACS activity in plants are not conserved in PHACS.

Amino Acid Sequence↗
PubMed2003

Comparative sequence and expression analyses of four mammalian VPS4 genes.

The VPS4 gene is a member of the AAA-family; it codes for an ATPase which is involved in lysosomal/endosomal membrane trafficking. VPS4 genes are present in virtually all eukaryotes. Exhaustive data mining of all available genomic databases from completely or partially sequenced organisms revealed the existence of up to three paralogues, VPS4a, -b, and -c. Whereas in the genome of lower eukaryotes like yeast only one VPS4 representative is present, we found that mammals harbour two paralogues, VPS4a and VPS4b. Most interestingly, the Fugu fish contains a third VPS4 paralogue (VPS4c). Sequence comparison of the three VPS4 paralogues indicates that the Fugu VPS4c displays sequence features intermediate between VPS4a and VPS4b. Using complete mammalian VPS4a and VPS4b cDNA clones as probes, genomic clones of both VPS4 paralogues in human and mouse were identified and sequenced. The chromosomal loci of all four VPS4 genes were determined by independent methods. A BLAST search of the human genome database with the human VPS4A sequence yielded a double match, most likely due to a faulty assembly of sequence contigs in the human draft sequence. Fluorescent in situ hybridization and radiation hybrid analyses demonstrated that human and mouse VPS4A/a and VPS4B/b are located on syntenic chromosomal regions. Northern blot and semi-quantitative reverse transcription analyses showed that mouse VPS4a and VPS4b are differentially expressed in different organs, suggesting that the two paralogues have developed different functional properties since their divergence. To investigate the subcellular distribution of the murine VPS4 paralogues, we transiently expressed various fluorescent VPS4 fusion proteins in mouse 3T3 cells. All tested VPS4 fusion proteins were found in the cytosol. Expression of dominant-negative mutant VPS4 fusion proteins led to their concentration in the perinuclear region. Co-expression of VPS4a-GFP and VPS4b-dsRed fusion proteins revealed a partial co-localization that was most prominent with mutant VPS4a and VPS4b proteins. A physical interaction between the mouse paralogues was also supported by two-hybrid analyses.

3T3 Cells↗
PubMed2003

Shadoo, a new protein highly conserved from fish to mammals and with similarity to prion protein.

We report evidence from cDNA isolation and expression analysis as well as analyses of genome, expressed sequence tag (EST), cDNA and expression databases for a new gene named SPRN (shadow of prion protein). SPRN comprises two exons, with the open reading frame (ORF) contained within exon 2, and codes for a protein of 130-150 amino acids named Shadoo (Japanese shadow), predicted to be extracellular and GPI-anchored. The SPRN gene was found in fish (zebrafish, Fugu) and mammals (mouse, rat, human). Conservation of order and transcription orientation of two proximal genes between fishes and mammals strongly indicates gene orthology. Sequence comparison shows: a highly conserved N-terminal signal sequence; Arg-rich basic region containing up to six tetrarepeats of consensus XXRG (where X is G, A or S); a hydrophobic region of 20 residues with strong homology to PrP; a less conserved C-terminal domain containing a conserved glycosylation motif; and a C-terminal peptide predicted to be a signal sequence for glycophosphotidylinositol (GPI)-anchor attachment. Fish Shadoos (Sho) show well conserved sequences (identity 54%) over 106 amino acids (zebrafish length), and conservation among the mammalian sequences is very high (identity 81-96%). The fish and mammalian sequences are also well conserved, particularly for zebrafish, to beyond the end of the hydrophobic sequence (identity 41-53%, 78 amino acids, zebrafish length). The overall structure appears closely related to prion proteins (PrPs), although the C-terminal domains of Shos are quite different from those of PrPs, for which conformational changes in mammals are implicated in disease. The structural similarity is particularly interesting given recent reports of three new genes with similarities to PrPs found in Fugu (PrP-like, PrP-461/stPrP-1 and stPrP-2) and other fish, but for which direct evolution to higher vertebrate PrPs is unlikely and for which no other mammalian homologues have been found. Database information indicates expression of SPRN in embryo, brain and retina of mouse and rat, hippocampus of human, and in embryo and retina of zebrafish, and we directly confirmed a strikingly specific expression of the mammalian (human, mouse, rat) transcripts in whole brain. This result together with some common structural features led to the suggestive hypothesis of a possible functional link between mammalian PrP and Sho proteins.

Amino Acid Sequence↗
PubMed1998

FRG1, a gene in the FSH muscular dystrophy region on human chromosome 4q35, is highly conserved in vertebrates and invertebrates.

The human FRG1 gene maps to human chromosome 4q35 and was identified as a candidate for facioscapulohumeral muscular dystrophy. However, FRG1 is apparently not causally associated with the disease and as yet, its function remains unclear. We have cloned homologues of FRG1 from two additional vertebrates, the mouse and the Japanese puffer fish Fugu rubripes, and investigated the genomic organization of the genes in the two species. The intron/exon structure of the genes is identical throughout the protein coding region, although the Fugu gene is five times smaller than the mouse gene. We have also identified FRG1 homologues in two nematodes; Caenorhabditis elegans and Brugia malayi. The FRG1 protein is highly conserved and contains a lipocalin sequence motif, suggesting it may function as a transport protein.

Amino Acid Sequence↗
PubMed1999

Isolation and characterisation of the retinoic acid receptor-alpha gene in the Japanese pufferfish, F. rubripes.

Nuclear hormone receptors (NRs) are ligand-inducible transcription factors that mediate critical functions in many species. The majority of novel NRs have hitherto been cloned from cDNA libraries by virtue of their homology to previously identified receptors. In this study, we validate a genomic DNA-based approach to isolating NRs by cloning the retinoic acid receptor-alpha (RARalpha) gene from the genome of the Japanese pufferfish, Fugu rubripes. The fRARalpha gene is more compact than its human and murine counterparts and demonstrates a highly conserved genomic organisation and amino acid sequence, generating two isoforms (fRARalpha1 and fRARalpha2) with divergent aminoterminal domains. In addition, a conserved regulatory element containing a retinoic acid response element was identified upstream of the fRARalpha2-specific exon, implying that retinoid induction of this isoform is evolutionarily conserved and critical to its function in vivo. We propose two uses for the Fugu genome in the study of NRs: the isolation of novel NRs that exhibit restricted spatio-temporal expression from genomic DNA and the identification of evolutionarily conserved promoter or intragenic regulatory DNA elements.

Amino Acid Sequence↗
PubMed2002

New 3' elements control Pax6 expression in the developing pretectum, neural retina and olfactory region.

Pax6 is a key transcriptional regulator in eye, olfactory system, forebrain, pituitary cerebellum, spinal cord and pancreas development. Alternative splicing, promoter usage and multiple enhancers regulate the complex Pax6 spatio-temporal expression pattern. Chromosomal rearrangements which abolish PAX6 gene expression have been characterised downstream of the coding region. Through evolutionary sequence comparison and transgenic reporter studies, we have identified a new Pax6 3' cis-regulatory region. This region, C1170 Box 123, contains three distinct modules of human-mouse sequence conservation, while only Box 1 is conserved to Fugu. Both the human and the orthologous Fugu sequence direct similar reporter gene expression in the developing pretectum, neural retina and olfactory region, indicating evolutionary conservation of Pax6 regulatory mechanisms despite the low level of overall sequence conservation.

3' Untranslated Regions↗
PubMed2002

Parathyroid hormone-related protein in lower vertebrates.

The genes for parathyroid hormone-related protein (PTHrP) have been cloned in two teleost fishes, cDNA of sea bream (Sparus aurata) and genomic DNA of puffer fish (Fugu rubripes). The gene sequences show that there is significant conservation of amino acid identity, with specific domains most highly conserved. The N-terminus, responsible for bone matrix lysis in mammals and chickens, is present in the fish genes with 52% sequence identity to higher vertebrate PTHrP peptides; the nuclear transporter region shares 73% identity, and the RNA-binding sequence is 65% identical. However, the peptides are shorter then mammalian PTHrP, lacking the C-terminus responsible for inhibition of osteoclast lytic activity, but they have an additional inserted sequence between amino acids 38 and 54 that is not present in higher vertebrate PTHrPs. The N-terminus 1-38 Fugu PTHrP proved to be hypercalcaemic in larval Sparus, suggesting that it may be a physiological regulator of calcium homeostasis in fish. Using homologous nucleotide probes for in situ hybridisation and reverse-transcription polymerase chain reaction (RT-PCR) of extracted RNA, PTHrP gene expression has been widely found in both developing and adult fish. Antiserum to the fish insert sequence demonstrated transcription of PTHrP in all stages of Sparus development, and also detected the same epitope in tissues of developing frog (Rana temporaria), indicating that this has been retained during evolution of the amphibia.

Amino Acid Sequence↗
PubMed1975

Multiple personality. A single case study with a 15 year follow-up.

A review of the literature relating to multiple personality is presented together with a study of a single case of hysterical aetiology that demonstrates the development of multiple personality from a fugue amnesic state. A re-examination of this case after 15 years without significant psychotherapeutic intervention demonstrates a tendency towards remission. The view that multiple personality is a form of fugue, not necessarily hysterical, in which an alternative personality is adopted and that this behaviour is reinforced by the attention that it receives, is discussed.

Adolescent↗