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Results for “regulatory evolution”

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PubMed2002

Neuronal organization of the melanin-concentrating hormone system in primitive actinopterygians: evolutionary changes leading to teleosts.

Hypothalamic melanin-concentrating hormone (MCH) neurones occur in all vertebrates and have an apparent neuromodulatory role. In teleost fish, however, MCH is used also as a neurohypophysial hormone, controlling skin color, and as a hypophysiotrophic peptide. This work describes the central location of immunoreactive MCH perikarya and their projections to the pituitary in a range of ancestral fish to determine the phylogenetic stage when the peptide adopted these roles. In all actinopterygians examined, including polypteriformes, chondrosteans, holosteans, and teleosts, immunoreactive fibers were abundant in the median eminence or, in the case of teleosts, within the pars distalis itself, suggesting MCH acquired a hypophysial regulatory role early in vertebrate evolution. MCH fibers appeared to be absent from the posterior neurohypophysis of the polypteriform Calamoichthys but were evident in this region in the chondrostean Acipensor, the holosteans Lepisosteus and Amia, and all teleosts, suggesting its use as a neurohypophysial hormone. The ability of MCH to induce skin pallor seems to have arisen at a later stage, probably in the preholosteans. This hormonal role coincides with the migration of MCH perikarya away from the ventricular surface and their enlargement into magnocellular neurones. In the higher teleosts, magnocellular hypothalamo-neurohypophysial neurones predominate in size and number, whereas smaller periventricular MCH neurones associated with the paraventricular organ, that are prominent in lampreys, early actinopterygians and tetrapods, are reduced in teleosts. The data suggest that, in teleost fish, earlier functions of the peptide may have become subordinate to its novel pigmentary role.

Animals↗

PubMed2005

Remembering the cell fate during cellular differentiation.

Higher eukaryote contains several hundreds of different cell types, each with a distinctive set of property defined by a unique gene expression pattern, even though every cell (with minor exception) shares the common genome. During cellular differentiation, the committed gene expression pattern is set up and propagated through numerous cell divisions. Therefore, cells must have evolved some elegant and inherent mechanisms to remember their expression states for the requirement of the stability of differentiation and development. Here we speculate a hypothetically cellular memory mechanism. In this hypothesis, the cell-cell variation during cellular differentiation may result from the inherent stochastic gene expression. The evolution of histone and distant regulatory sequences change the parameters of expression stochasticity. S-phase-dependent gene activation and epigenetic marks on chromatin provide means to discriminate transcriptionally active and repressive states. Eventually, mitotic memory mechanisms have been developed through which these expression states are transmitted through numerous cell divisions.

Animals↗

PubMedDate not supplied

Molecular genetics of APUDomas.

It is tempting to speculate that genetic studies of the human APUDomas, particularly those of a hereditary nature, may ultimately provide valuable clues to the molecular basis of malignant transformation in cells of all types, uncover the mechanisms responsible for tumor progression, and perhaps decipher the signals important in the differentiation of normal neural crest-derived tissue. Generally, several strategies have been used in the genetic analysis of these tumors with success. These include (1) cytogenetic examination of recurring chromosomal abnormalities in hopes of pinpointing critical neighboring growth regulatory sequences important in tumor evolution, (2) identification of dominant acting oncogenes in tumor cells, (3) search for recessive inactivated suppressor genes that may regulate cell growth by analyzing tumors for loss of heterozygosity (LOH), and (4) genetic linkage studies of kindreds affected with familial APUDomas to identify and subsequently characterize the predisposition gene using a positional or functional cloning approach. The results of these strategies as they have been employed in the investigation of cutaneous malignant melanoma (CMM), the dysplastic nevus syndrome (DNS), and the multiple endocrine neoplasia (MEN) syndromes are summarized.

Apudoma↗

PubMed1976

Gene action in fish of tetraploid origin. III. Ribosomal DNA amount in cyprinid fish.

Phylogenetically diploid and tetraploid cyprinid fish species have cells of very similar volumes and protein contents. This finding has prompted us to postulate a regulatory system established during the evolution of the tetraploids leading to a diploid state of genic expression. It was proposed that this might be accounted for by a selective loss of ribosomal genes. RNA-DNA hybridization experiments, however, reveal a clear-cut 1:2 relationship of ribosomal DNA amounts between the diploid and the tetraploid species.

Animals↗

PubMed1990

Molecular cloning and sequence determination of four different cDNA species coding for alpha-subunits of G proteins from Xenopus laevis oocytes.

A cDNA library prepared from Xenopus laevis oocytes in lambda gt10 was screened with a mixture of three oligonucleotide probes designed to detect sequences found in different mammalian genes coding for alpha-subunits of G-proteins. In addition to a clone coding for a G alpha o-type subunit previously reported [(1989) FEBS Lett. 244, 188-192] four additional clones have been found coding for different G alpha protein subunits. By comparison with mammalian alpha-subunits, these oocyte cDNAs correspond to two closely related G alpha s-1a, to a G alpha i-1 and to a G alpha i-3 species. The derived amino acid sequences showed that both G alpha s species contain 379 residues, corresponding to the short species without the serine residue and with a calculated Mr of 42720. The G alpha i-1 gene encodes a 354 amino acid protein with an Mr of 39,000 and the G alpha i-3 encodes an incomplete open reading frame of 345 residues, lacking the first 9 amino acid residues at the NH2 terminus. All these G alpha-subunits showed high identity with their respective mammalian counterparts (75-80%), indicating a great degree of conservation through the evolution and the important cellular regulatory function that they play.

Amino Acid Sequence↗

PubMed1992

Analysis of a polyketide synthesis-encoding gene cluster of Streptomyces curacoi.

A gene cluster homologous to the beta-ketoacyl synthase-encoding gene, actl, was cloned by Southern blot hybridization from Streptomyces curacoi, and a 5469-bp fragment was sequenced. Analysis of the sequence revealed seven open reading frames (ORFs). A striking similarity to the whiE locus (encoding spore pigment synthesis) of Streptomyces coelicolor was found throughout the whole cluster, with conservation of the size and position of the seven ORFs. The structure of these two gene clusters suggests that they have a common origin, although the lower similarity in the noncoding regions suggests that the regulatory regions have diverged through evolution.

Amino Acid Sequence↗

PubMed2004

Structural delineation of the calcineurin-NFAT interaction and its parallels to PP1 targeting interactions.

Calcineurin is a phosphoprotein phosphatase that channels intracellular Ca signals into multiple biological pathways. Calcineurin is known to interact directly with its substrate nuclear factor of activated T cells (NFAT or NFATc), with other substrates, and with several targeting and scaffold proteins including AKAP79 and Cabin1/cain. The calcineurin-NFAT interaction depends on recognition of a PxIxIT sequence motif present in NFAT-family proteins and in certain other calcineurin-interacting proteins. Here, we define the structural basis for the interaction of calcineurin with NFAT and with other proteins possessing the PxIxIT motif. The calcineurin-PxIxIT contact has a direct parallel in the contact of protein phosphatase 1 with its regulatory proteins, suggesting that the evolution of these related phosphatases involved local remodelling of an ancestral docking site.

Amino Acid Sequence↗

PubMed1999

The preplacement evaluation.

Over the past 25 years, the preplacement evaluation has undergone considerable evolution under the influence of regulatory and economic pressures. Formally used by some employers to screen out applicants who might have represented the mere possibility of a future work-related injury, the modern-day preplacement evaluation is legally restricted to only two determinations: (1) whether the individual can perform essential job functions with or without accommodation and (2) whether the individual represents a direct threat to himself or herself or others. Truly enlightened companies also recognize that other benefits accrue from a properly designed, conscientiously performed preplacement evaluation, perhaps the most important of which is to promote worker health, in the certain recognition that healthy employees are more productive ones. This benefit may be the true purpose of the preplacement evaluation and its most enduring, tangible benefit.

Confidentiality↗

PubMed2001

Plant development: the benefits of a change of scene.

Multicellular organisms are composed of groups of different cell types. The importance in the evolution of cellular diversity of regulatory changes in genes that control cell specification has been revealed by a recent study of developmental genes in Arabidopsis.

Animals↗

PubMed2003

Motifs, modules and games in bacteria.

Global explorations of regulatory network dynamics, organization and evolution have become tractable thanks to high-throughput sequencing and molecular measurement of bacterial physiology. From these, a nascent conceptual framework is developing, that views the principles of regulation in term of motifs, modules and games. Motifs are small, repeated, and conserved biological units ranging from molecular domains to small reaction networks. They are arranged into functional modules, genetically dissectible cellular functions such as the cell cycle, or different stress responses. The dynamical functioning of modules defines the organism's strategy to survive in a game, pitting cell against cell, and cell against environment. Placing pathway structure and dynamics into an evolutionary context begins to allow discrimination between those physical and molecular features that particularize a species to its surroundings, and those that provide core physiological function. This approach promises to generate a higher level understanding of cellular design, pathway evolution and cellular bioengineering.

Animals↗

PubMed2004

The endocannabinoid system: physiology and pharmacology.

The endogenous cannabinoid system is an ubiquitous lipid signalling system that appeared early in evolution and which has important regulatory functions throughout the body in all vertebrates. The main endocannabinoids (endogenous cannabis-like substances) are small molecules derived from arachidonic acid, anandamide (arachidonoylethanolamide) and 2-arachidonoylglycerol. They bind to a family of G-protein-coupled receptors, of which the cannabinoid CB(1) receptor is densely distributed in areas of the brain related to motor control, cognition, emotional responses, motivated behaviour and homeostasis. Outside the brain, the endocannabinoid system is one of the crucial modulators of the autonomic nervous system, the immune system and microcirculation. Endocannabinoids are released upon demand from lipid precursors in a receptor-dependent manner and serve as retrograde signalling messengers in GABAergic and glutamatergic synapses, as well as modulators of postsynaptic transmission, interacting with other neurotransmitters, including dopamine. Endocannabinoids are transported into cells by a specific uptake system and degraded by two well-characterized enzymes, the fatty acid amide hydrolase and the monoacylglycerol lipase. Recent pharmacological advances have led to the synthesis of cannabinoid receptor agonists and antagonists, anandamide uptake blockers and potent, selective inhibitors of endocannabinoid degradation. These new tools have enabled the study of the physiological roles played by the endocannabinoids and have opened up new strategies in the treatment of pain, obesity, neurological diseases including multiple sclerosis, emotional disturbances such as anxiety and other psychiatric disorders including drug addiction. Recent advances have specifically linked the endogenous cannabinoid system to alcoholism, and cannabinoid receptor antagonism now emerges as a promising therapeutic alternative for alcohol dependence and relapse.

Alcoholism↗

PubMed2002

Beyond tandem repeats: complex pattern structures and distant regions of similarity.

MOTIVATION: Tandem repeats (TRs) are associated with human disease, play a role in evolution and are important in regulatory processes. Despite their importance, locating and characterizing these patterns within anonymous DNA sequences remains a challenge. In part, the difficulty is due to imperfect conservation of patterns and complex pattern structures. We study recognition algorithms for two complex pattern structures: variable length tandem repeats (VLTRs) and multi-period tandem repeats (MPTRs). RESULTS: We extend previous algorithmic research to a class of regular tandem repeats (RegTRs). We formally define RegTRs, as well as two important subclasses: VLTRs and MPTRs. We present algorithms for identification of TRs in these classes. Furthermore, our algorithms identify degenerate VLTRs and MPTRs: repeats containing substitutions, insertions and deletions. To illustrate our work, we present results of our analysis for two difficult regions in cattle and human data which reflect practical occurrences of these subclasses in GenBank sequence data. In addition, we show the applicability of our algorithmic techniques for identifying Alu sequences, gene clusters and other distant regions of similarity. We illustrate this with an example from yeast chromosome I.

Algorithms↗

PubMedDate not supplied

Changes in the activity and the polypeptide composition of the oxygen-evolving complex in photosystem II of tobacco leaves infected with cucumber mosaic virus strain Y.

The amount of 22- and 23-kDa polypeptides in a 23-kDa protein family, which plays a regulatory role in photosynthetic oxygen evolution, decreased significantly during the progress of appearance of chlorotic spots in cucumber mosaic virus strain Y (CMV[Y])-inoculated tobacco (Nicotiana tabacum 'Ky57') leaves (Plant Mol. Biol. 16:689-698, 1991). The present study was conducted to determine if the amount of other polypeptides of the oxygen-evolving complex and the oxygen-evolving activity also decreased in CMV(Y)-inoculated tobacco leaves. The amount of a 33-kDa polypeptide, which is essential to oxygen evolution, did not decrease in CMV(Y)-inoculated leaves showing early symptoms, although the amount of 22- and 23-kDa polypeptides began to decrease. However, comparative analysis of electron transport in thylakoid membranes indicated that the oxygen-evolving activity in CMV(Y)-inoculated tobacco leaves was only partly reduced, compared with the activity in CMV(O)-inoculated tobacco leaves which did not show clear symptoms. Partial inhibition of the oxygen-evolving activity, by a differential decrease in the amount of polypeptides of the oxygen-evolving complex, seems to be associated with the primary molecular process of symptom expression in CMV(Y)-inoculated tobacco leaves.

Amino Acid Sequence↗

PubMed1995

GTPases: a family of molecular switches and clocks.

Members of the GTPase superfamily share a core domain with a conserved three-dimensional structure and a common GTPase cycle, but perform a wide variety of regulatory tasks in eukaryotic cells. Evolution has created functional diversity from the conserved GTPase structure in two principal ways: (i) by combining in the product of a single gene the core GTPase domain attached to one or more additional folded domains; (ii) by building around a core GTPase an assembly of proteins encoded by different genes. Analysis of the patterns of conserved amino acid side chains on surfaces of G alpha proteins reveals interfaces with other proteins in the G-protein signal linking device.

Animals↗

PubMed2005

Genomic analysis of LexA binding reveals the permissive nature of the Escherichia coli genome and identifies unconventional target sites.

Genomes of eukaryotic organisms are packaged into nucleosomes that restrict the binding of transcription factors to accessible regions. Bacteria do not contain histones, but they have nucleoid-associated proteins that have been proposed to function analogously. Here, we combine chromatin immunoprecipitation and high-density oligonucleotide microarrays to define the in vivo DNA targets of the LexA transcriptional repressor in Escherichia coli. We demonstrate a near-universal relationship between the presence of a LexA sequence motif, LexA binding in vitro, and LexA binding in vivo, suggesting that a suitable recognition site for LexA is sufficient for binding in vivo. Consistent with this observation, LexA binds comparably to ectopic target sites introduced at various positions in the genome. We also identify approximately 20 novel LexA targets that lack a canonical LexA sequence motif, are not bound by LexA in vitro, and presumably require an additional factor for binding in vivo. Our results indicate that, unlike eukaryotic genomes, the E. coli genome is permissive to transcription factor binding. The permissive nature of the E. coli genome has important consequences for the nature of transcriptional regulatory proteins, biological specificity, and evolution.

Bacterial Proteins↗

PubMed2005

Role of Snf1p in regulation of intracellular sorting of the lactose and galactose transporter Lac12p in Kluyveromyces lactis.

The protein kinase Snf1/AMPK plays a central role in carbon and energy homeostasis in yeasts and higher eukaryotes. To work out which aspects of the Snf1-controlled regulatory network are conserved in evolution, the Snf1 requirement in galactose metabolism was analyzed in the yeast Kluyveromyces lactis. Whereas galactose induction was only delayed, K. lactis snf1 mutants failed to accumulate the lactose/galactose H+ symporter Lac12p in the plasma membran,e as indicated by Lac12-green fluorescent protein fusions. In contrast to wild-type cells, the fusion protein was mostly intracellular in the mutant. Growth on galactose and galactose uptake could be restored by the KHT3 gene, which encodes a new transporter of the HXT subfamily of major facilitators These findings indicate a new role of Snf1p in regulation of sugar transport in K. lactis.

Biological Transport↗

PubMed2006

Identification and analysis of DNA-binding transcription factors in Bacillus subtilis and other Firmicutes--a genomic approach.

BACKGROUND: Bacillus subtilis is one of the best-characterized organisms in Gram-positive bacteria. It represents a paradigm of gene regulation in bacteria due its complex life style (which could involve a transition between stages as diverse as vegetative cell and spore formation). In order to gain insight into the organization and evolution of the B. subtilis regulatory network and to provide an alternative framework for further studies in bacteria, we identified and analyzed its repertoire of DNA-binding transcription factors in terms of their abundance, family distribution and regulated genes. RESULTS: A collection of 237 DNA-binding Transcription Factors (TFs) was identified in B. subtilis, half of them with experimental evidence. 59% of them were predicted to be repressors, 17% activators, 17% were putatively identified as dual regulatory proteins and the remaining 6.3% could not be associated with a regulatory role. From this collection 56 TFs were found to be autoregulated, most of them negatively, though a significant proportion of positive feedback circuits were also identified. TFs were clustered into 51 regulatory protein families and then traced on 58 genomes from Firmicutes to detect their presence. From this analysis three families were found conserved in all the Firmicutes; fifteen families were distributed in all Firmicutes except in the phyla Mollicutes; two were constrained to Bacillales and finally two families were found to be specific to B. subtilis, due to their specie specific distribution. Repression seems to be the most common regulatory mechanism in Firmicutes due to the high proportion of repressors in the detected collection in these genomes. In addition, six global regulators were defined in B. subtilis based on the number and function of their regulated genes. CONCLUSION: In this work we identified and described the characteristics associated to the repertoire of DNA-binding TFs in B. subtilis. We also quantified their abundance, family distribution, and regulatory roles in the context of Firmicutes. This work should not only contribute to our understanding of the regulation of gene expression in bacteria from the perspective of B. subtilis but also provide us the basis for comprehensive modeling of transcriptional regulatory networks in Firmicutes.

Bacillus subtilis↗

PubMed1999

Life among the primitives: protein O-phosphatases in prokaryotes.

Prokaryotes contain at least five distinct families of protein O-phosphatases, including AceK, the chimeric isocitrate dehydrogenase kinase/phosphatase, and four protein phosphatase families first identified and characterized in Eukaryotes. The latter consist of the PPP and PPM families of protein-serine/threonine phosphatases, and the low molecular weight and conventional families of protein-tyrosine phosphatases. Prokaryotic protein O-phosphatases participate in the regulation of metabolic processes and the transduction of environmental signals. Certain pathogenic bacteria employ protein-tyrosine phosphatases as virulence factors, injecting them into host cells where they enzymatically perturb the phosphorylation state of proteins therein. While our understanding of protein O-phosphorylation events in Prokaryotes only now is emerging from its infancy, their phylogenetic diversity and malleability to genetic manipulation render these "simple'" organisms powerful vehicles for answering fundamental questions concerning the origins and evolution of this key biological regulatory mechanism.

Phosphoprotein Phosphatases↗