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At least 1,279 records · Page 71Linked to original sources
PubMed1999

Getting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters.

ATP-binding cassette (ABC) systems, also called traffic ATPases, are found in eukaryotes and prokaryotes and almost all participate in the transport of a wide variety of molecules. ABC systems are characterized by a highly conserved ATPase module called here the ABC module, involved in coupling transport to ATP hydrolysis. We have used the sequence of one of the first representatives of bacterial ABC transporters, the MalK protein, to collect 250 closely related sequences from a nonredundant protein sequence database. The sequences collected by this objective method are all known or putative ABC transporters. After having eliminated short protein sequences and duplicates, the 197 remaining sequences were subjected to a phylogenetic analysis based on a mutational similarity matrix. An unrooted tree for these modules was found to display two major branches, one grouping all collected uptake systems and the other all collected export systems. This remarkable disposition strongly suggests that the divergence between these two functionally different types of ABC systems occurred once in the history of these systems and probably before the differentiation of prokaryotes and eukaryotes. We discuss the implications of this finding and we propose a model accounting for the generation and the diversification of ABC systems.

ATP-Binding Cassette Transporters↗
PubMed2006

Petaloid-type cms in carrot is not associated with expression of atp8 (orfB).

Two different atp8 reading frames with divergent C-terminal extensions were identified in a sterility-inducing mitochondrial type (mitotype) of carrot; examination of three fertility-inducing mitotypes revealed atp8 reading frames that were either terminated at a position conserved among other plant atp8 genes or continued with unique C-terminal extensions. Similarities between the C-terminal extensions suggest ancient common ancestry, but the level of sequence divergence implies lack of functional conservation. Northern analysis indicated that the C-terminal extensions are transcribed and are present within the primary atp8 transcripts. Western analysis revealed that the products of the two extended atp8 reading frames encoded by the sterility-inducing mitotype are significantly smaller than those predicted by complete translation of their C-terminal extensions, but are slightly larger than the products from unextended reading frames. No alterations were observed in atp8 transcripts or proteins isolated from flowers of the sterility-inducing mitotype that were phenotypically fertile as a result of segregation for nuclear fertility-restoring Ms or Rf alleles, and thus, there is no evidence that expression of atp8 is directly involved in the petaloid cms phenotype in carrot.

3' Untranslated Regions↗
PubMed1991

Secondary structure as a constraint on the evolution of a plant viral satellite RNA.

The genetic variability and evolution of the satellite RNA (satRNA) of cucumber mosaic virus (CMV) was analyzed. Twenty-five CMV-satRNAs compared clustered into three main groups, and no correlation was found between genetic proximity and other characteristics (pathogenicity, geographical origin) of the satRNAs. Values for the number of nucleotide substitutions per site between any two satRNAs suggest that divergence is checked by functional constraints. The analysis of mutations relative to an ancestral sequence, and the number of substitutions per site at first, second and third positions of codons in putative open reading frames, show that the variation of CMV-satRNAs does not follow a pattern typical of coding sequences, and indicates that preservation of the sequence of encoded products is not a constraint to evolution. On the other hand, when the observed variation was analyzed relative to a secondary structure model proposed for CMV-satRNAs, several lines of evidence indicated that the maintenance of the secondary structure is a constraint to evolution: the number of substitutions per site, the number of point insertions and deletions and the number of base substitutions that would disrupt base-pairing were significantly higher for unpaired than for base-paired positions. Also, compensatory mutations at base-paired positions occurred more frequently than expected from random. The results suggest that CMV-satRNAs are non-coding, functional RNAs whose biology would be determined by their direct interaction with components of the host and/or the helper virus.

Base Composition↗
PubMed1984

Genes in S. cerevisiae encoding proteins with domains homologous to the mammalian ras proteins.

The ras genes, which were first identified by their presence in RNA tumor viruses and which belong to a highly conserved gene family in vertebrates, have two close homologs in yeast, detectable by Southern blotting. We have cloned both genes (RAS1 and RAS2) from plasmid libraries and determined the complete nucleotide sequence of their coding regions. They encode proteins with nearly 90% homology to the first 80 positions of the mammalian ras proteins, and nearly 50% homology to the next 80 amino acids. Yeast RAS1 and RAS2 proteins are more homologous to each other, with about 90% homology for the first 180 positions. After this, at nearly the same position that the mammalian ras proteins begin to diverge from each other, the two yeast ras proteins diverge radically. The yeast ras proteins, like the proteins encoded by the mammalian genes, terminate with the sequence cysAAX, where A is an aliphatic amino acid. Thus the yeast ras proteins have the same overall structure and interrelationship as the family of mammalian ras proteins. The domains of divergence may correspond to functional domains of the ras proteins. Monoclonal antibody directed against mammalian ras proteins immunoprecipitates protein in yeast cells containing high copy numbers of the yeast RAS2 gene.

Amino Acid Sequence↗
PubMed1987

Verbal expression of right cerebrovascular accident patients: convergent and divergent language.

This investigation examined the role of the right hemisphere in language expression. Three groups of 12 subjects each--right CVAs, left CVAs, and controls--performed convergent and divergent language tasks of naming, function, and connected speech. For all convergent tasks and for number of words, number of message units, and fluency in divergent connected speech, controls surpassed both brain-damaged groups, who performed similarly. For the other divergent tasks, controls were superior to the brain-damaged groups, but the right CVAs outperformed the left CVAs. In general, verbal expression problems of right-hemisphere-damaged patients were almost as severe as those of left-hemisphere-damaged patients.

Adult↗
PubMed2005

A redox switch hypothesis for the origin of two light reactions in photosynthesis.

Photosynthesis provides energy in the Earth's biosphere and oxygen in its atmosphere. For oxygen to be produced, two different light reactions must operate simultaneously and in series. Known anaerobic, photosynthetic bacteria contain one or other of these photosystems, but never both. Here, I propose that the two photosystems diverged, in structure and function, from a common ancestor, within a single, continuous, anaerobic lineage. In such cells, living examples of which are predicted, the two photosystems are isoenzymes encoded by orthologous genes under co-ordinated, redox regulatory control. A redox switch responds to defined environmental conditions and selects which set of genes is expressed. In these cells, the two photosystems are thus synthesised at different times. It is further proposed that the origin of oxygen-evolving photosynthesis was a simple mutation that disabled the redox switch, permitting simultaneous expression of the two sets of genes. The two, newly co-existing photosystems became connected by shared electron carriers, allowing generation of electrochemical potential high enough to oxidise water; an inexhaustible supply of reductant; and the selective advantages and pressures of an aerobic world.

Evolution, Molecular↗
PubMed2004

The crystal structure of feruloyl esterase A from Aspergillus niger suggests evolutive functional convergence in feruloyl esterase family.

As a component of the array of enzymes produced by micro-organisms to deconstruct plant cell walls, feruloyl esterases hydrolyze phenolic groups involved in the cross-linking of arabinoxylan to other polymeric structures. This is important for opening the cell wall structure, making material more accessible to glycosyl hydrolases. Here, we describe the first crystal structure of the non-modular type-A feruloyl esterase from Aspergillus niger (AnFaeA) solved at 2.5A resolution. AnFaeA displays an alpha/beta hydrolase fold similar to that found in fungal lipases and different from that reported for other feruloyl esterases. Crystallographic and site-directed mutagenesis studies allow us to identify the catalytic triad (Ser133-His247-Asp194) that forms the catalytic machinery of this enzyme. The active-site cavity is confined by a lid (residues 68-80), on the analogy of lipases, and by a loop (residues 226-244) that confers plasticity to the substrate-binding site. The lid presents a high ratio of polar residues, which in addition to a unique N-glycosylation site stabilises the lid in an open conformation, conferring the esterase character to this enzyme. A putative model for bound 5,5'-diferulic acid-linked arabinoxylan has been built, pointing to the more relevant residues involved in substrate recognition. Comparison with structurally related lipases reveals that subtle amino acid and conformational changes within a highly conserved protein fold may produce protein variants endowed with new enzymatic properties, while comparison with functionally related proteins points to a functional convergence after evolutionary divergence within the feruloyl esterases family.

Aspergillus niger↗
PubMed1995

Divergent effects of chronic amiodarone administration on systolic and diastolic function in patients with heart disease.

The purpose of this study was to determine the effects of chronic amiodarone treatment on systolic and diastolic function in patients with cardiac disease undergoing treatment for resistant ventricular arrhythmias. Previous studies have shown that chronic amiodarone treatment either has no effect or increases left ventricular ejection fraction, but the effects on diastolic properties of the ventricle have not been defined. Twelve male patients were given loading doses of amiodarone followed by a maintenance regimen. Serial measurements of heart rate, blood pressure, and indexes of systolic and diastolic function were measured by Doppler echocardiographic techniques at baseline conditions and at 2, 8, and 12 weeks of drug therapy. Changes in altered thyroid state were excluded by serial determinations of thyroid function. Amiodarone increased left ventricular ejection fraction (+16%, p < 0.01 by 8 weeks), decreased presystolic ejection period/left ventricular ejection time (-12%, p < 0.01 by 8 weeks), and increased velocity of circumferential fiber shortening (+22%, p < 0.05 by 8 weeks). Amiodarone decreased mitral inflow velocity peak E/peak A (-7%, p < 0.01 by 12 weeks), and increased deceleration and isovolumic relaxation times incrementally (+36% [p < 0.001] and +23% [p < 0.001], respectively, at 12 weeks). Chronically administered amiodarone can improve systolic function and exert a negative lusitropic action in patients with heart disease.

Aged↗
PubMed1997

Denervation-induced sprouting of intact peripheral afferents into the cuneate nucleus of adult rats.

In adult monkeys with dorsal rhizotomies extending from the second cervical (C2) to the fifth thoracic (T5) vertebrae, cortex deprived of its normal inputs regained responsiveness to inputs conveyed by intact peripheral afferents from the face [T.P. Pons, P.E. Garraghty, A.K. Ommaya, J.H. Kaas, E. Taub, M. Mishkin, Massive reorganization of the primary somatosensory cortex after peripheral sensory deafferentation, Science 252 (1991) 1857-1860]. It has been suggested that the extent of this massive topographic reorganization may be due to the establishment of novel connections between intact afferents and neurons denervated after dorsal rhizotomy [P.E. Garraghty, D.P. Hanes, S.L. Florence, J.H. Kaas, Pattern of peripheral deafferentation predicts reorganizational limits in adult primate somatosensory cortex, Somatosens. Motor Res. 11 (1994) 109-117]. Using adult rats with comparably extensive dorsal rhizotomies, we employed anatomical tracing techniques to address this possibility. Subcutaneous hindpaw injections of horseradish peroxidase conjugated to either wheat germ agglutinin or cholera toxin subunit B revealed aberrant expansions of gracile projections into the cuneate and, in one case, external cuneate nucleus within three months of the deafferentation. It seems plausible that such modest sprouting of ascending projections at the level of the brainstem may form functional connections which, through divergence, ultimately drive a larger population of neurons in cortex. This new growth may well account for both the substantial cortical reorganization observed in the 'Silver Spring monkeys' [T.P. Pons, P.E. Garraghty, A.K. Ommaya, J.H. Kaas, E. Taub, M. Mishkin, Massive reorganization of the primary somatosensory cortex after peripheral sensory deafferentation, Science 252 (1991) 1857-1860] and the 'referred sensation' phenomena (see J.P. Donoghue, Plasticity of adult sensorimotor representations, Curr. Opin. Neurobiol., 5 (1995) 749-754 for review) reported to follow proximal limb amputations in humans.

Afferent Pathways↗
PubMed2000

Genomic exploration of the hemiascomycetous yeasts: 12. Kluyveromyces marxianus var. marxianus.

As part of the comparative genomics project 'GENOLEVURES', we studied the Kluyveromyces marxianus var. marxianus strain CBS712 using a partial random sequencing strategy. With a 0.2 x genome equivalent coverage, we identified ca. 1300 novel genes encoding proteins, some containing spliceosomal introns with consensus splice sites identical to those of Saccharomyces cerevisiae, 28 tRNA genes, the whole rDNA repeat, and retrotransposons of the Ty1/2 family of S. cerevisiae with diverged Long Terminal Repeats. Functional classification of the K. marxianus genes, as well as the analysis of the paralogous gene families revealed few differences with respect to S. cerevisiae. Only 42 K. marxianus identified genes are without detectable homolog in the baker's yeast. However, we identified several genetic rearrangements between these two yeast species.

Ascomycota↗
PubMed2005

Spectrin, alpha-actinin, and dystrophin.

Spectrin family proteins represent an important group of actin-bundling and membrane-anchoring proteins found in diverse structures from yeast to man. Arising from a common ancestral alpha-actinin gene through duplications and rearrangements, the family has increased to include the spectrins and dystrophin/utrophin. The spectrin family is characterized by the presence of spectrin repeats, actin binding domains, and EF hands. With increasing divergence, new domains and functions have been added such that spectrin and dystrophin also contain specialized protein-protein interaction motifs and regions for interaction with membranes and phospholipids. The acquisition of new domains also increased the functional complexity of the family such that the proteins perform a range of tasks way beyond the simple bundling of actin filaments by alpha-actinin in S. pombe. We discuss the evolutionary, structural, functional, and regulatory roles of the spectrin family of proteins and describe some of the disease traits associated with loss of spectrin family protein function.

Actinin↗
PubMedDate not supplied

The differences between the structural repertoires of VH germ-line gene segments of mice and humans: implication for the molecular mechanism of the immune response.

Although human and murine antibodies are similar when considering their diversification strategies, they differ in the proportion by which kappa and lambda type chains are present in their receptive V, repertoires. It has been shown that this difference implies a divergence in the structural repertoire of the kappa and lambda genes of these species. Nonetheless, the differences in VH have not been systematically studied. In this paper a systematic characterization of the VH structural repertoire of mice is made, so that a comparison with the VH structural repertoire of humans, described in detail elsewhere, could be properly accomplished. Our study shows the structural repertoire of mice to be dominated by canonical structure class 1-2 (approximately 60%), while in humans the dominant one is class 1-3 (approximately 40%). Analysis of the evolutionary relationships between human and mice suggest that this divergence may have a functional meaning. The implications of such findings are discussed.

Amino Acid Sequence↗
PubMed1998

Development of engineered vaccines effective against structurally related bacterial superantigens.

Staphylococcal and streptococcal superantigens are exotoxins that may be linked to many human pathologies involving impaired immune functions. Despite considerable sequence divergence, bacterial superantigens share extensive secondary and tertiary structure and use similar structural strategies to bind major histocompatibility complex class II receptors. We produced by site-directed mutagenesis of the conserved receptor-binding surfaces of the superantigens staphylococcal enterotoxins A and B. These vaccines protected immunized mice and rhesus monkeys from lethal toxic shock. In addition, antibodies produced against each superantigen recognized and neutralized distantly related superantigens. This antibody cross-reactivity was additive in that mixtures of superantigens used in immunization were more effective than single-component vaccines in protecting mice from challenges with individual or mixed superantigens. We conclude that an optimal combination of these genetically attenuated superantigen vaccines may protect against all structurally related superantigens.

Animals↗
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↗
PubMed1997

Structure, chromosomal localization and expression of mouse genes encoding type III Reg, RegIII alpha, RegIII beta, RegIII gamma.

Reg (regenerating gene), first isolated from a rat regenerating islet cDNA library, is expressed in regenerating islet beta-cells. Recently, it has been revealed that Reg and Reg-related genes constitute a multigene family, Reg family, which consists of three subtypes (type I, II, III) based on the primary structures of the encoded proteins of the genes. In mouse, type I and type II Reg genes (i.e. RegI and RegII gene) have so far been isolated. In the present study, the complete nucleotide (nt) sequences of the cDNAs and genes encoding murine type III Reg (regenerating gene product), RegIII alpha, RegIII beta and RegIII gamma were determined. RegIII alpha, RegIII beta and RegIII gamma encode 175-, 175- and 174-amino acid (aa) proteins, respectively, with 60-70% homology. All three genes are composed of six exons and five introns spanning approx. 3 kb, and exhibit distinctive structural features unique for members of the Reg gene family. All the mouse Reg genes, RegIII alpha, RegIII beta, RegIII gamma, RegI and RegII, are assigned to the adjacent site of chromosome 6C by fluorescence in situ hybridization (FISH). RegIII alpha, RegIII beta and RegIII gamma were expressed weakly in pancreas, strongly in intestinal tract, but not in hyperplastic islets, whereas both RegI and RegII were expressed in hyperplastic islets. These results suggest that genes of the mouse Reg family are derived from a common ancestor gene by several gene duplications, and have obtained divergency in expression and function in the process of genetic evolution.

Amino Acid Sequence↗
PubMed2002

Plasticity of enzyme active sites.

The expectation is that any similarity in reaction chemistry shared by enzyme homologues is mediated by common functional groups conserved through evolution. However, detailed enzyme studies have revealed the flexibility of many active sites, in that different functional groups, unconserved with respect to position in the primary sequence, mediate the same mechanistic role. Nevertheless, the catalytic atoms might be spatially equivalent. More rarely, the active sites have completely different locations in the protein scaffold. This variability could result from: (1) the hopping of functional groups from one position to another to optimize catalysis; (2) the independent specialization of a low-activity primordial enzyme in different phylogenetic lineages; (3) functional convergence after evolutionary divergence; or (4) circular permutation events.

Amino Acid Sequence↗
PubMedDate not supplied

Nuclear import and export of proteins: the molecular basis for intracellular signaling.

A family of latent cytoplasmic transcription factors termed Stats are activated by a variety of cytokines, and are then translocated into the nucleus where they activate transcription. Recent advances in nuclear protein import have shown that the extracellular signal-dependent nuclear import of Stat1 is mediated via complex formation with NPI-1 (a member of the alpha subunit family) and the beta subunit of the nuclear pore-targeting complex, and a small GTPase, Ran. The unique transport pathway of Stat1, which is different from that of the SV40T-antigen, indicates that a complex divergence exists in the function of transport factors and transport pathways.

Animals↗
PubMed2000

The effect of subdivision on variation at multi-allelic loci under balancing selection.

Simulations are used to investigate the expected pattern of variation at loci under different forms of multi-allelic balancing selection in a finite island model of a subdivided population. The objective is to evaluate the effect of restricted migration among demes on the distribution of polymorphism at the selected loci at equilibrium, and to compare the results with those expected for a neutral locus. The results show that the expected number of alleles maintained, and numbers of nucleotide differences between alleles, are relatively insensitive to the migration rate, and differentiation remains low even under very restricted migration. However, nucleotide divergence between copies of functionally identical alleles increases sharply when migration decreases. These results are discussed in relation to published surveys of allelic diversity in MHC and plant self-incompatibility systems, and to the possibility of inferring ancient population genetic events and processes. In addition, it is shown that, for sporophytic self-incompatibility systems, it is not necessarily true in a subdivided population that recessive alleles are more frequent than dominant ones.

Alleles↗