SEARCH · PubMed Health

Results for “regulatory evolution”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources

PubMed2004

Computational comparative analyses of alternative splicing regulation using full-length cDNA of various eukaryotes.

We previously reported a computational approach to infer alternative splicing patterns from Mus musculus full-length cDNA clones and microarray data. Although we predicted a large number of unreported splice variants, the general mechanisms regulating alternative splicing were yet unknown. In the present study, we compared alternative exons and constitutive exons in terms of splice-site strength and frequency of potential regulatory sequences. These regulatory features were further compared among five different species: Homo sapiens, M. musculus, Arabidopsis thaliana, Oryza sativa, and Drosophila melanogaster. Solid statistical validations of our comparative analyses indicated that alternative exons have (1) weaker splice sites and (2) more potential regulatory sequences than constitutive exons. Based on our observations, we propose a combinatorial model of alternative splicing mechanisms, which suggests that alternative exons contain weak splice sites regulated alternatively by potential regulatory sequences on the exons.

Alternative Splicing↗

PubMed2000

HOX Pro: a specialized database for clusters and networks of homeobox genes.

It is now clear that the homeobox motif is well conserved across metazoan phyla. It has been established experimentally that a subset of genes containing this motif plays key roles in the orchestration of gene expression during development. Auto- and cross-regulatory functional interactions join homeobox genes into genetic networks. We have developed a specialized database HOX-Pro in order to arrange all available data on structure, function, phylogeny and evolution of Hox genes, Hox clusters and Hox networks. Its primary location is http://www.iephb.nw.ru/hoxpro. The database is also mirrored at http://www.mssm.edu/molbio/hoxpro. The HOX-Pro database is aimed at: (i) analysis and classification of regulatory and coding regions in diverse homeobox and related genes; (ii) comparative analysis of organization of 'Hox-based' genetic networks in the sea urchin Strongylocentrotus purpuratus, the fruit fly Drosophila melanogaster and the mouse Mus musculus; and (iii) analysis of phylogeny and evolution of homeobox genes and clusters.

Animals↗

PubMed2004

Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis.

Histone deacetylases (HDACs) modify core histones and participate in large regulatory complexes that both suppress and enhance transcription. Recent studies indicate that some HDACs can act on non-histone proteins as well. Interest in these enzymes is growing because HDAC inhibitors appear to be promising therapeutic agents against cancer and a variety of other diseases. Thus far, 11 members of the HDAC family have been identified in humans, but few have been characterized in detail. To better define the biological function of these proteins, make maximal use of studies performed in other systems, and assist in drug development efforts, we have performed a phylogenetic analysis of all HDAC-related proteins in all fully sequenced free-living organisms. Previous analyses have divided non-sirtuin HDACs into two groups, classes 1 and 2. We find that HDACs can be divided into three equally distinct groups: class 1, class 2, and a third class consisting of proteins related to the recently identified human HDAC11 gene. We term this novel group "class 4" to distinguish it from the unrelated "class 3" sirtuin deacetylases. Analysis of gene duplication events indicates that the common ancestor of metazoan organisms contained two class 1, two class 2, and a single class 4 HDAC. Examination of HDAC characteristics in light of these evolutionary relationships leads to functional predictions, among them that self-association is common among HDAC proteins. All three HDAC classes (including class 4) exist in eubacteria. Phylogenetic analysis of bacterial HDAC relatives suggests that all three HDAC classes precede the evolution of histone proteins and raises the possibility that the primary activity of some "histone deacetylase" enzymes is directed against non-histone substrates.

Eukaryotic Cells↗

PubMed2004

The revolution of the biology of the genome.

Sequence data of entire eukaryotic genomes and their detailed comparison have provided new evidence on genome evolution. The major mechanisms involved in the increase of genome sizes are polyploidization and gene duplication. Subsequent gene silencing or mutations, preferentially in regulatory sequences of genes, modify the genome and permit the development of genes with new properties. Mechanisms such as lateral gene transfer, exon shuffling or the creation of new genes by transposition contribute to the evolution of a genome, but remain of relatively restricted relevance. Mechanisms to decrease genome sizes and, in particular, to remove specific DNA sequences, such as blocks of satellite DNAs, appear to involve the action of RNA interference (RNAi). RNAi mechanisms have been proven to be involved in chromatin packaging related with gene inactivation as well as in DNA excision during the macronucleus development in ciliates.

Animals↗

PubMed1994

Evolution of the gastrointestinal endocrine system (with special reference to gastrin and CCK).

The evolution of gut endocrine cells can be seen to have depended in the first instance on the expression of genes encoding regulatory peptides in cells that had evolved the regulated pathway of secretion. It seems probable that the endocrine cells made use of molecules and mechanisms that first emerged in early nervous systems. However, by the start of the vertebrate line of evolution, most of the major families of gut hormones were already found in association with endocrine cells. A single common class of receptor with seven transmembrane domains and acting via association with G-proteins transduces many (perhaps all) gut peptide actions. The duplication and divergence of receptors and peptides can now be traced, in outline at least, for gastrin and CCK in vertebrates. Even in phylogenetically similar groups such as birds and mammals, quite different molecular approaches have been applied to solving the same physiological problem. Evolution of the modern gastrointestinal control system evidently depended in this case both on molecular evolution of peptides and receptors and on cells expressing the genes encoding them.

Amino Acid Sequence↗

PubMed1994

Conserved regulatory elements in the type I DNA topoisomerase gene promoters of mouse and man.

The gene for mammalian type I DNA topoisomerase is constitutively expressed, but also regulated by a number of external stimuli. We compared the nucleotide sequences of the human and the mouse topoisomerase I gene promoters because promoter elements, essential for basic as well as regulated gene expression, should be conserved during evolution. We found that proximal upstream sequences are highly conserved and include potential binding sites for ubiquitous transcription factors, a regulatory CRE site as well as two novel promoter elements that have been shown to be important for the expression of the human gene. The more distal parts of the upstream sequences are less well conserved but include two regions that are almost identical in the human and the mouse gene. One of these regions contains a binding site for a basic-helix-loop-helix/leucine-zipper protein, and the other contains an AT-rich element with the potential for DNA bending.

Animals↗

PubMed2004

Gene therapy progress and prospects: transcription regulatory systems.

The clinical efficacy and safety as well as the application range of gene therapy will be broadened by developing systems capable of finely modulating the expression of therapeutic genes. Transgene regulation will be crucial for maintaining appropriate levels of a gene product within the therapeutic range, thus preventing toxicity. Moreover, the possibility to modulate, stop or resume transgene expression in response to disease evolution would facilitate the combination of gene therapy with more conventional therapeutic modalities. The development of ligand-dependent transcription regulatory systems is thus of great importance. Here, we summarize the most recent progress in the field.

Anti-Bacterial Agents↗

PubMed1992

Evolution of the primate lentiviruses: evidence from vpx and vpr.

The genomes of the four primate lentiviral groups are complex and contain several regulatory or accessory genes. Two of these genes, vpr and vpx, are found in various combinations within the four groups and encode proteins whose functions have yet to be elucidated. Comparison of the encoded protein sequences suggests that the vpx gene within the HIV-2 group arose by the duplication of an ancestral vpr gene within this group. Evolutionary distance analysis showed that both genes were well conserved when compared with viral regulatory genes, and indicated that the duplication occurred at approximately the same time as the HIV-2 group and the other primate lentivirus groups diverged from a common ancestor. Furthermore, although the SIVagm vpx proteins are homologous to the HIV-2 group vpx proteins, there are insufficient grounds from sequence analysis for classifying them as vpx proteins. Because of their similarity to the vpr proteins of other groups, we suggest reclassifying the SIVagm vpx gene as a vpr gene. This creates a simpler and more uniform picture of the genomic organization of the primate lentiviruses and allows the genomic organization of their common precursor to be defined; it probably contained five accessory genes: tat, rev, vif, nef and vpr.

Amino Acid Sequence↗

PubMed2003

Genetics and the making of Homo sapiens.

Understanding the genetic basis of the physical and behavioural traits that distinguish humans from other primates presents one of the great new challenges in biology. Of the millions of base-pair differences between humans and chimpanzees, which particular changes contributed to the evolution of human features after the separation of the Pan and Homo lineages 5-7 million years ago? How can we identify the 'smoking guns' of human genetic evolution from neutral ticks of the molecular evolutionary clock? The magnitude and rate of morphological evolution in hominids suggests that many independent and incremental developmental changes have occurred that, on the basis of recent findings in model animals, are expected to be polygenic and regulatory in nature. Comparative genomics, population genetics, gene-expression analyses and medical genetics have begun to make complementary inroads into the complex genetic architecture of human evolution.

Animals↗

PubMed2002

Developmental evolution: Hox proteins ring the changes.

The evolution of body form is believed to involve changes in expression of developmental genes, largely through changes in cis-regulatory elements. Recent studies suggest that changes in the sequences of key developmental regulators, such as the Hox proteins, may also play an important role.

Animals↗

PubMed2003

Comparison of the genome sequences of Listeria monocytogenes and Listeria innocua: clues for evolution and pathogenicity.

Listeria monocytogenes, an invasive opportunistic, food-borne pathogen, remains one of the leading causes of mortality from food-borne infections. The recently determined complete genome sequences of L. monocytogenes strain EGDe and of that of the closely related non-pathogenic species Listeria innocua strain CLIP11262 enhance our knowledge of the genetic basis of the virulence of L. monocytogenes and advance our understanding of the evolution of these Listeria species. Both genomes encode a high number of surface, transport and regulatory proteins. Comparison of the genome organisation revealed a perfect synteny between the two Listeria genomes. Comparison with other closely related bacteria also showed a high conservation in genome organisation among the Listeria, Staphylococcus and Bacillus group of low G+C content bacteria. Distinct G+C content of a number of strain-specific genes suggests intensive lateral gene transfer. The identification of a 55-kb locus encoding proteins with high homology to Salmonella enterica serovar Typhimurium vitamin B(12) synthesis proteins as well as those necessary for degradation of ethanolamine and propanediol further indicates acquisition of a complete metabolic pathway by horizontal gene transfer and a probable role of this locus in anaerobic growth in the host.

Anaerobiosis↗

PubMed2003

Masters change, slaves remain.

Sex determination offers an opportunity to address many classic questions of developmental biology. In addition, because sex determination evolves rapidly, it offers an opportunity to investigate the evolution of genetic hierarchies. Sex determination in Drosophila melanogaster is controlled by the master regulatory gene, Sex lethal (Sxl). DmSxl controls the alternative splicing of a downstream gene, transformer (tra), which acts with tra2 to control alternative splicing of doublesex (dsx). DmSxl also controls its own splicing, creating an autoregulatory feedback loop that ensures expression of Sxl in females, but not males. A recent paper has shown that in the dipteran Ceratitis capitata later (downstream) steps in the regulatory hierarchy are conserved, while earlier (upstream) steps are not. Cctra is regulated by alternative splicing and apparently controls the alternative splicing of Ccdsx. However, Cctra is not regulated by CcSxl. Instead it appears to autoregulate in a manner similar to the autoregulation seen with DmSxl.

Animals↗

PubMed2006

PAMP recognition and the plant-pathogen arms race.

Plants have evolved systems analogous to animal innate immunity that recognise pathogen-associated molecular patterns (PAMPs). PAMP detection is an important component of non-host resistance in plants and serves as an early warning system for the presence of potential pathogens. Binding of a PAMP to the appropriate pattern recognition receptor leads to downstream signalling events and, ultimately, to the induction of basal defence systems. To overcome non-host resistance, pathogens have evolved effectors that target specific regulatory components of the basal defence system. In turn, this has led to the evolution in plants of cultivar-specific resistance mediated by R proteins, which guard the targets of effectors against pathogen manipulation; the arms race continues.

Flagellin↗

PubMed2026

Loss, persistence and reversal of phenotypic traits.

The irreversibility of complex trait loss has long been a tenet of evolutionary biology. However, this idea is increasingly at odds with the numerous documented exceptions across the Tree of Life. We synthesise this growing body of evidence across a diverse array of taxa and traits, exploring the evolutionary conditions that enable evolutionary reversal. By integrating macroevolutionary, genetic, and developmental information, we argue that trait reversal is commonly fostered by some form of persistence in the generative developmental pathway of the lost trait. We identify three overarching modes of trait reversal and support them with multiple case studies: by pleiotropy (the involvement of the same generative components in other traits and/or functions), by plasticity (environment-dependent expression of the trait) and by hemiplasy (persistence in another lineage, followed by reticulate evolution). We also examine important affinities between trait reversal and evolutionary novelties, undermining a neat distinction between what is old and what is new in evolution. This survey may provide a useful framework for future explorations of the developmental mechanisms underlying these still overlooked macroevolutionary dynamics.

Phenotype↗

PubMed1988

Sequence similarities of the protamine genes: implications for regulation and evolution.

With the recent availability of the primary structural data for the trout, bovine, and mouse protamine genes, a detailed comparison of their structures has been made. This has revealed extensive conservation of potentially biologically significant regions. An inverse correlation is apparent between gene copy number and the number of sequence-distinct protamines synthesized with the number of CP-box-like (CCYPCCC) putative transcription modulating sequences situated 5' to these genes. A common nucleotide sequence 5' to the CP-box-like putative transcription modulating sequence(s) at the end of a common region has been identified. It is postulated that this is the testis-specific protamine P1 transcription regulator sequence. Evidence based on sequence similarity is also provided for the existence of a primordial protamine gene and a scheme for the evolution of vertebrate protamine genes is proposed.

Amino Acid Sequence↗

PubMed1991

Effect of ligand binding on the tryptic digestion pattern of rat brain hexokinase: relationship of ligand-induced conformational changes to catalytic and regulatory functions.

The Type I isozyme of rat hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is comprised of N- and C-terminal domains, associated with regulatory and catalytic functions, respectively. Extensive sequence similarity between the domains is consistent with evolution of the enzyme by gene duplication and fusion. Cleavage at tryptic sites located in the C-terminal domain is markedly sensitive to ligands present during digestion, while analogous sites in the N-terminal domain are either resistant to trypsin or unaffected by the presence of ligands. These results imply a lack of structural equivalence between the N- and C-terminal domains, with the overall structure of the N-terminal domain being "tighter" and with a major component of ligand-induced conformational changes being focused in the C-terminal domain. Based on a previously proposed structure for brain hexokinase, protection by substrate hexoses is attributed to substrate-induced closing of a cleft in the C-terminal domain. Similar protection at C-terminal cleavage sites results from binding of inhibitory hexose-6-phosphates to the N-terminal domain. In addition, hexose-6-phosphates evoke cleavage at a site, T5, located in a region that has been associated with binding of ATP to the C-terminal domain. Thus, alterations in this region, coupled with reduced accessibility resulting from cleft closure, may account for the mutually exclusive binding of inhibitory hexose-6-phosphates and substrate ATP. In the absence of Mg2+, all nucleoside triphosphates examined (ATP, UTP, CTP, and GTP) protected against digestion by trypsin. In contrast, ATP-Mg2+ stabilized the C-terminal domain but destabilized the N-terminal domain, while the chelated forms of the other nucleoside triphosphates were similar to the unchelated forms in their effect on proteolysis; the unique response to ATP-Mg2+ reflects the specificity for ATP as a substrate.

Adenosine Triphosphate↗

PubMed1982

A walk in the chorion locus of Bombyx mori.

We have recovered overlapping clones that represent in the aggregate a contiguous segment of chromosomal DNA 270 kb in length, or probably one third of the chorion locus of Bombyx mori. Approximately 70 genes have been identified, the majority of which are arranged in coordinately expressed pairs. The nonidentical genes expressed in the late period of choriogenesis are clustered within a single, 130 kb region, which is flanked by regions containing genes that are active during the middle developmental period. The late genes encode two families of high-cysteine proteins; the evolutionarily persistent clustering of these families contrasts sharply with the extensive sequence diversification of the structural genes and their flanking DNA elements. We discuss the possible regulatory significance of the clustered arrangement, as well as certain features of multigene family evolution.

Base Sequence↗

PubMed1996

AACR-ISREC joint symposium "Cancer and the cell cycle' January 17-20, 1996, Lausanne, Switzerland.

It has become apparent in the recent years that defects in regulatory systems of the eukaryotic cell cycle contribute, in a major way, to the evolution of a neoplastic phenotype in mammalian cells. The American Association of Cancer Research (AACR) and the Swiss Institute for Experimental Cancer Research (ISREC) jointly organized a meeting, held last January in Lausanne/Switzerland, to discuss recent results in cell cycle research and their implications for cancer.

Cell Cycle↗