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Results for “functional divergence”

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At least 487 records · Page 27Linked to original sources
PubMed2005

The WD-repeat protein GRWD1: potential roles in myeloid differentiation and ribosome biogenesis.

A cDNA fragment originally identified in U-937 cells as a vitamin D(3)-regulated gene is here designated the glutamate-rich WD-repeat (GRWD1) gene. WD-repeat proteins are a class of functionally divergent molecules that cooperate with other proteins to regulate cellular processes. GRWD1 encodes a 446-amino-acid protein containing a glutamate-rich region followed by four WD repeats. The yeast homologue of GRWD1, Rrb1, has been shown to be an essential protein involved in ribosome biogenesis. Northern analysis of GRWD1 message levels in the myeloid cell line HL-60 undergoing differentiation induced by vitamin D(3) or retinoic acid demonstrate downregulation coincident with slowing of cellular proliferation. A siRNA designed to downregulate GRWD1 similarly results in a decrease in cellular proliferation within 293 cells. Metabolic labeling of cells expressing the siRNA to GRWD1 shows a decrease in global protein synthesis. Finally, nuclear fractionation studies show cosedimentation of GRWD1 with preribosomal complexes, as well as the WD-repeat-containing protein Bop1, which has previously been implicated in ribosome biogenesis. These studies suggest that within mammalian cells GRWD1 plays a role in ribosome biogenesis and during myeloid differentiation its levels are regulated.

Base Sequence↗
PubMed2006

Gene duplication and inactivation in the HPRT gene family.

Hypoxanthine phosphoribosyltransferase (HPRT1) is a key enzyme in the purine salvage pathway, and mutations in HPRT1 cause Lesch-Nyhan disease. The studies described here utilized targeted comparative mapping and sequencing, in conjunction with database searches, to assemble a collection of 53 HPRT1 homologs from 28 vertebrates. Phylogenetic analysis of these homologs revealed that the HPRT gene family expanded as the result of ancient vertebrate-specific duplications and is composed of three groups consisting of HPRT1, phosphoribosyl transferase domain containing protein 1 (PRTFDC1), and HPRT1L genes. All members of the vertebrate HPRT gene family share a common intron-exon structure; however, we have found that the three gene groups have distinct rates of evolution and potentially divergent functions. Finally, we report our finding that PRTFDC1 was recently inactivated in the mouse lineage and propose the loss of function of this gene as a candidate genetic basis for the phenotypic disparity between HPRT-deficient humans and mice.

Animals↗
PubMed1992

Isolation of a cDNA clone encoding the RNase-superfamily-related gene highly expressed in chicken bone marrow cells.

The RNase gene superfamily combines functionally divergent proteins which share statistically significant sequence similarity. Known members assigned to this family include secretory and nonsecretory RNases; angiogenin; eosinophil cationic protein; eosinophil-derived neurotoxin; sialic-acid binding lectin and anti-tumor protein P-30. We report the cDNA cloning of the chicken RNase Super Family Related (RSFR) gene that is specifically overexpressed in normal bone marrow cells and bone marrow-derived AMV transformed monoblasts. It codes for a 139 amino acid protein with a putative signal peptide and remarkable conservation of active-site residues, other residues known to be important for substrate binding and catalytic activity and half-cystine residues common for all RNase family members. Phylogenetic tree analysis shows that RSFR defines a new group of genes within the family. We also conclude that an amino acid sequence block CKXXNTF(X) 11C is a "shortest RNase superfamily signature" which is both necessary and sufficient to identify all previously recognized family members as well as chicken RSFR.

Amino Acid Sequence↗
PubMed2003

Structural and mechanistic insight from high resolution structures of archaeal rhodopsins.

Lipidic cubic phase-grown crystals yielded high resolution structures of a number of archaeal retinal proteins, the molecular mechanisms of which are being revealed as structures of photocycle intermediates become available. The structural basis for bacteriorhodopsin's mechanism of proton pumping is discussed, revealing a well-synchronized sequence of molecular events. Comparison with the high resolution structures of the halide pump halorhodopsin, as well as with the receptor sensory rhodopsin II, illustrates how small and localized structural changes result in functional divergence. Fundamental principles of energy transduction and sensory reception in the archaeal rhodopsins, which may have relevance to other systems, are discussed.

Archaeal Proteins↗
PubMed2003

Pharmacology of neuronal background potassium channels.

Background or leak conductances are a major determinant of membrane resting potential and input resistance, two key components of neuronal excitability. The primary structure of the background K(+) channels has been elucidated. They form a family of channels that are molecularly and functionally divergent from the voltage-gated K(+) channels and inward rectifier K(+) channels. In the nervous system, the main representatives of this family are the TASK and TREK channels. They are relatively insensitive to the broad-spectrum K(+) channel blockers tetraethylammonium (TEA), 4-aminopyridine (4-AP), Cs(+), and Ba(2+). They display very little time- or voltage-dependence. Open at rest, they are involved in the maintenance of the resting membrane potential in somatic motoneurones, brainstem respiratory and chemoreceptor neurones, and cerebellar granule cells. TASK and TREK channels are also the targets of many physiological stimuli, including intracellular and extracellular pH and temperature variations, hypoxia, bioactive lipids, and neurotransmitter modulation. Integration of these different signals has major effects on neuronal excitability. Activation of some of these channels by volatile anaesthetics and by other neuroprotective agents, such as riluzole and unsaturated fatty acids, illustrates how the neuronal background K(+) conductances are attractive targets for the development of new drugs.

Animals↗
PubMed2003

Comparison of the properties of prostaglandin H synthase-1 and -2.

Biosynthesis of prostanoid lipid signaling agents from arachidonic acid begins with prostaglandin H synthase (PGHS), a hemoprotein in the myeloperoxidase family. Vertebrates from humans to fish have two principal isoforms of PGHS, termed PGHS-1 and-2. These two isoforms are structurally quite similar, but they have very different pathophysiological roles and are regulated very differently at the level of catalysis. The focus of this review is on the structural and biochemical distinctions between PGHS-1 and-2, and how these differences relate to the functional divergence between the two isoforms.

Amino Acid Sequence↗
PubMed1998

The evolution of 'bricolage'.

The past ten years of developmental genetics have revealed that most of our genes are shared by other species throughout the animal kingdom. Consequently, animal diversity might largely rely on the differential use of the same components, either at the individual level through divergent functional recruitment, or at a more integrated level, through their participation in various genetic networks. Here, we argue that this inevitably leads to an increase in the interdependency between functions that, in turn, influences the degree to which novel variations can be tolerated. In this 'transitionist' scheme, evolution is neither inherently gradualist nor punctuated but, instead, progresses from one extreme to the other, together with the increased complexity of organisms.

Animals↗
PubMed2000

Paired inhibitory and triggering NK cell receptors for HLA class I molecules.

Human natural killer (NK) cells specifically interact with major histocompatibility complex (MHC) class I molecules employing different receptor systems, shared with subsets of alphabeta and gammadelta T lymphocytes. Killer cell immunoglobulin-like receptors (KIRs) recognize groups of human leukocyte antigen (HLA) class Ia proteins displaying common structural features at the alpha-1 domain; among them, KIR2DL4 has been proposed to specifically interact with the class Ib molecule HLA-G1. Members of a related family of immunoglobulin (Ig)-like receptors (ILT2 or LIR-1 and ILT4 or LIR-2), expressed by other leukocyte lineages, interact with a broad spectrum of class Ia molecules and HLA-G1. On the other hand, CD94/NKG2-A(-C) and NKG2D lectin-like receptors, respectively, recognize the class Ib molecules HLA-E and MICA. A recurrent finding within the different receptor families is the existence of pairs of homologous molecules that often share the same ligands but display divergent functions. Inhibitory receptors tend to exhibit an affinity for HLA molecules higher than their activating counterparts. Recruitment of SH2 domain-bearing tyrosine phosphatases (SHP) by cytoplasmic phosphorylated immunoreceptor tyrosine-based inhibition motifs (ITIMs) is a crucial event for the inhibitory signalling pathway. By contrast, triggering receptors assemble with homodimers of immune tyrosine-based activation motif (ITAM)-bearing adaptor molecules (i.e., DAP12, CD3 xi) that engage tyrosine kinases (ZAP70 and syk).

Histocompatibility Antigens Class I↗
PubMed2003

Molecular and biochemical analysis of the system regulating the lytic/lysogenic cycle in the pneumococcal temperate phage MM1.

The temperate phage MM1 forms stable lysogens in Streptococcus pneumoniae. We report here the first characterization of the lysogenic control region in Pneumococcus which contains two functional divergent promoters (P(R) and P(L)). MM1 encodes a 14-kDa cI protein (CI) that appears to be responsible for maintaining the lysogenic state in Pneumococcus since it prevents elongation of the transcripts controlled by P(R) and P(L).

Bacteriophages↗
PubMed2000

Molecular evolution of color vision of zebra finch.

We have isolated and sequenced the RH1(Tg), RH2(Tg), SWS2(Tg), and LWS(Tg) opsin cDNAs from zebra finch retinas. Upon binding to 11-cis-retinal, these opsins regenerate the corresponding photosensitive molecules, visual pigments. The absorption spectra of visual pigments have a broad bell shape, with the peak being called lambda(max). Previously, SWS1(Tg) opsin cDNA was isolated from zebra finch retinal RNA, expressed in cultured COS1 cells, reconstituted with 11-cis-retinal, and the lambda(max) of the resulting visual pigment was shown to be 359nm. Here, the lambda(max) values of the RH1(Tg), RH2(Tg), SWS2(Tg), and LWS(Tg) pigments are determined to be 501, 505, 440, and 560nm, respectively. Molecular evolutionary analyses suggest that specific amino acid replacements in the SWS1 and SWS2 pigments, resulting from accelerated evolution, must have been responsible for their functional divergences among the avian pigments.

Amino Acid Sequence↗
PubMed2001

Gene duplication and mobile genetic elements in the morning glories.

We review gene duplication and subsequent structural and functional divergence in the anthocyanin biosynthesis genes in the Japanese and common morning glories and discuss their evolutionary implications. These plants appear to contain at least six copies of the CHS gene and three tandem copies of the DFR gene. Of these, the CHS-D and DFR-B genes are mainly responsible for flower pigmentation and mutations in these genes confer white flowers. We compared the genomic sequences of these duplicated genes between the two morning glories and found small mobile element-like sequences (MELSs) and direct repeats (DRs) in introns and intergenic regions. The results indicate that the MELS elements and DRs play significant roles in divergence after gene duplication. We also discuss DNA rearrangements occurring before and after speciation of these morning glories. DNA transposable elements belonging to the Ac/Ds or En/Spm families have acted as major spontaneous mutagens in these morning glories. We also describe the structural features of the first Mu-related element found in the morning glories and polymorphisms found in the same species.

Alcohol Oxidoreductases↗
PubMed2002

The human transcription factor activation protein-2 gamma (AP-2gamma): gene structure, promoter, and expression in mammary carcinoma cell lines.

Human activation protein-2 gamma (hAP-2gamma) is a key developmental transcription factor. It has been implicated in mammary carcinogenesis through its regulation of HER-2/neu proto-oncogene and estrogen receptor gene The hAP-2gamma gene is located on human chromosome 20q13.2. We cloned this gene, deduced its genomic structure, and mapped and analyzed its promoter. The hAP-2gamma gene contains seven exons. Primer extension analysis and 5'-rapid amplification of complementary DNA ends studies show that there is a single transcription start site 232 nt upstream of the translational start codon. The promoter lacks canonical binding sites for basal transcription factors such as TATA and CCAAT boxes, but contains a cluster of CpG islands and may rely on an initiator element for transcription. Deletion analyses of the promoter and chloramphenicol acetyl transferase reporter gene assays indicate that the sequence between -746 and -575 is important for its expression in mammary carcinoma cell lines. The hAP-2gamma gene is marginally activated in these cells suggesting that increased transcription partly contributes to its abundance. Architecture of the gene and promoter strikingly resembles that of hAP-2alpha, which is located on a different chromosome, suggesting a cognate origin. hAP-2alpha and hAP-2gamma have some common and some distinct roles in cells, and are likely the remarkable results of gene duplication, translocation and functional divergence through evolution.

Base Sequence↗
PubMed2003

Comparison of gene representation in midguts from two phytophagous insects, Bombyx mori and Ips pini, using expressed sequence tags.

Midgut proteins may provide new molecular targets for insect control. This could be particularly important for some pests, such as pine bark beetles, which are difficult to control by conventional methods. Expressed sequence tags (ESTs) provide information about the activity of a particular tissue, and, in the case of pest insects, may quickly identify potential targets. We present here an EST project representing 574 tentative unique genes (TUGs) expressed in the midgut of the male pine engraver beetle, Ips pini. This tissue uses the mevalonate pathway to produce the monoterpenoid pheromone component, ipsdienol, de novo in response to juvenile hormone (JH) III. Comparison of our ESTs with those previously isolated from larval silkmoth (Bombyx mori) midguts revealed interesting similarities and differences in gene representation that correlate with the conserved and divergent functions of these two tissues. For example, seven mevalonate pathway genes were represented in the I. pini ESTs, while none were found from B. mori. This type of comparison may assist the identification of species-specific targets for future pest control strategies.

Animals↗
PubMed2006

Mutator transposon in maize and MULEs in the plant genome.

Mutator (Mu) is by far the most mutagenic plant transposon. The high frequency of transposition and the tendency to insert into low copy sequences for such transposon have made it the primary means by which genes are mutagenized in maize (Zea mays L.). Mus like elements (MULEs) are widespread among angiosperms and multiple-diverged functional variants can be present in a single genome. MULEs often capture genetic sequences. These Pack-MuLEs can mobilize thousands of gene fragments, which may have had a significant impact on host genome evolution. There is also evidence that MULEs can move between reproductively isolated species. Here we present an overview of the discovery, features and utility of Mu transposon. Classification of Mu elements and future directions of related research are also discussed. Understanding Mu will help us elucidate the dynamic genome.

DNA Transposable Elements↗
PubMed1998

The zebrafish Pax3 and Pax7 homologues are highly conserved, encode multiple isoforms and show dynamic segment-like expression in the developing brain.

This study describes the isolation and characterization of zebrafish homologues of the mammalian Pax3 and Pax7 genes. The proteins encoded by both zebrafish genes are highly conserved (>83%) relative to the known mammalian sequences. Also the neural expression patterns during embryogenesis are very similar to the murine homologues. However, observed differences in neural crest and mesodermal expression relative to mammals could reflect some functional divergence in the development of these tissues. For the zebrafish Pax7 protein we report the first full-length amino acid sequences in vertebrates and show the existence of three additional isoforms which have truncations in the homeodomain and/or the C-terminal region. These novel variants provide evidence for additional isoform diversity of vertebrate Pax proteins.

Amino Acid Sequence↗
PubMed1997

The Pbx family of proteins is strongly upregulated by a post-transcriptional mechanism during retinoic acid-induced differentiation of P19 embryonal carcinoma cells.

Retinoic acid (RA) induces expression of genes encoding the Hox family of transcription factors, whose differential expression orchestrates developmental programs specifying anterior-posterior structures during embryogenesis. Hox proteins bind DNA as monomers and heterodimers with Pbx proteins. Here we show that RA upregulates Pbx protein abundance coincident with transcriptional activation of Hox genes in P19 embryonal carcinoma cells undergoing neuronal differentiation. However, in contrast to Hox induction, Pbx upregulation is predominantly a result of post-transcriptional mechanisms. Interestingly, Pbx1, Pbx2, and Pbx3 exhibit different profiles of upregulation, suggesting possible functional divergence. The parallel upregulation of Pbx and Hox proteins in this model suggests an important role for transcriptional control by Pbx-Hox heterodimers during neurogenesis, and argues for precise control by RA.

Animals↗
PubMed1998

Transcriptional control of Drosophila bicoid by Serendipity delta: cooperative binding sites, promoter context, and co-evolution.

Concentration of maternal BICOID (BCD) establishes the anterior pattern in the Drosophila embryo. Successive deletions in the bcd promoter allowed us to localize an enhancer sequence in the 5'-UTR and a down-regulating element downstream of the ATG initiator codon, and identify a 49 bp region sufficient to drive transcription of a reporter gene specifically in nurse cells. This fragment contains two binding sites for the Serendipity (Sry) d zinc finger activator, that mediate its cooperative binding. Both sites (sdbs) are essential for bcd expression. Further analysis showed that the bcd promoter configuration is decisive for Sry d activating function. Replacement of sdbs by binding sites for Sry b, the Sry d paralog, restores bcd transcription in sry d mutant ovaries, demonstrating that the functional divergence between these two proteins during evolution was mainly driven by changes in their DNA-specific recognition properties, resulting in the control of separate developmental pathways.

Animals↗
PubMed1999

Rearranging gastrulation in the name of yolk: evolution of gastrulation in yolk-rich amniote eggs.

Gastrulating birds and mammals form a primitive streak in lieu of a circular blastopore, and a conspicuous underlying tissue layer, the hypoblast. In an attempt to understand the evolution of these amniote characteristics, pregastrula and gastrulation stages in selected amniotes are compared with the more ancestral situation in amphibians. At blastula/blastoderm stages, the overall fate maps and the arrangement of tissues around the organizer are rather similar, as is exemplified by a comparison of gene expression and fate maps in the frog and chick. Compared with amphibians, however, the eggs of reptiles, birds and monotreme mammals have a disproportionately large yolk that alters gastrulation morphology. During amphibian gastrulation, the organizer moves from anterior to posterior, to lay down the dorsal axis around the vegetal hemisphere (Arendt, D., Nübler-Jung, K., 1997. Dorsal or ventral: similarities in fate maps and gastrulation patterns in annelids, arthropods and chordates. Mech. Dev. 61, 1-15). In contrast, in amniote eggs, the large yolk impedes the organizer from moving around the entire vegetal hemisphere so that axis formation begins and ends at the same side of the egg. This has apparently provoked an evolutionary transformation of an amphibian-like blastopore, first into the 'blastoporal canal' of reptiles, and then into the birds' and mammals' primitive streak. The blastopore divides into two functionally divergent parts, one as the site of mesoderm internalization ('intraembryonic blastopore') and the other as the site of ectodermal epiboly ('extraembryonic blastopore'). The hypoblast is proposed to derive from the 'endodermal wedge' that is seen already in the amphibian gastrula. Hypoblast formation would then represent a special kind of gastrulation movement that also exists in the amphibians, and for which the term 'hypoboly' is introduced.

Amnion↗