Biomedical subjects

Genomics

Find indexed PubMed genomics citations. Search gene expression, sequencing and genetic variation in titles, abstracts and supplied subjects, then open the PubMed record.

Follow this topic with RSS

At least 1,675 records · Page 93Linked to original sources

PubMed2003

Variation of the genome size estimate with environmental conditions in Drosophila melanogaster.

BACKGROUND: Genome size is known to exhibit interspecies differences, but also to vary between populations within a given species and even between individual cells within an organism. Major differences have often been reported and attributed to differences in measurement conditions, in internal controls of genome size, and in the stains used. Flow cytometry using intercalating dyes is the most attractive method for measuring genome size. METHODS: We estimated relative genome size of nuclei from heads of Drosophila melanogaster adult males using a FACScalibur flow cytometer and propidium iodide. RESULTS: We have shown that the genome size estimates depended on the temperature and humidity of the rearing medium and decreased with age in adult flies. There were large differences in genome size estimates between the vials in which the flies were maintained, but only slight variations within the vials, supporting the idea that the size estimate depends on the fly rearing conditions. Changes in the temperature of the solution of head nuclei analyzed by the cytometer also influenced the genome size estimate. CONCLUSIONS: These findings clearly show that the environmental conditions under which the flies were reared influence the genome size estimate, perhaps as a result of a change in the accessibility of the DNA to the fluorochrome. Caution is therefore called for when estimating genome size. Experimental artifact rather than adaptation may account for some of the correlations between genome size and environmental conditions reported in the literature.

Animals↗

PubMed2003

Phylogenetic analyses alone are insufficient to determine whether genome duplication(s) occurred during early vertebrate evolution.

The widely accepted notion that two whole-genome duplications occurred during early vertebrate evolution (the 2R hypothesis) stems from the fact that vertebrates often possess several genes corresponding to a single invertebrate homolog. However the number of genes predicted by the Human Genome Project is less than twice as many as in the Drosophila melanogaster or Caenorhabditis elegans genomes. This ratio could be explained by two rounds of genome duplication followed by extensive gene loss, by a single genome duplication, by sequential local duplications, or by a combination of any of the above. The traditional method used to distinguish between these possibilities is to reconstruct the phylogenetic relationships of vertebrate genes to their invertebrate orthologs; ratios of invertebrate-to-vertebrate counterparts are then used to infer the number of gene duplication events. The lancelet, amphioxus, is the closest living invertebrate relative of the vertebrates, and unlike protostomes such as flies or nematodes, is therefore the most appropriate outgroup for understanding the genomic composition of the last common ancestor of all vertebrates. We analyzed the relationships of all available amphioxus genes to their vertebrate homologs. In most cases, one to three vertebrate genes are orthologous to each amphioxus gene (median number=2). Clearly this result, and those of previous studies using this approach, cannot distinguish between alternative scenarios of chordate genome expansion. We conclude that phylogenetic analyses alone will never be sufficient to determine whether genome duplication(s) occurred during early chordate evolution, and argue that a "phylogenomic" approach, which compares paralogous clusters of linked genes from complete amphioxus and human genome sequences, will be required if the pattern and process of early chordate genome evolution is ever to be reconstructed.

Animals↗

PubMed2001

Comparative genomics reveals close genetic relationships between phages from dairy bacteria and pathogenic Streptococci: evolutionary implications for prophage-host interactions.

The genome of the highly pathogenic M1 serotype Streptococcus pyogenes isolate SF370 contains eight prophage elements. Only prophage SF370.1 could be induced by mitomycin C treatment. Prophage SF370.3 showed a 33.5-kb-long genome that closely resembled the genome organization of the cos-site temperate Siphovirus r1t infecting the dairy bacterium Lactococcus lactis. The two-phage genomes shared between 60 and 70% nucleotide sequence identity over the DNA packaging, head and tail genes. Analysis of the SF370.3 genome revealed mutations in the replisome organizer gene that may prevent the induction of the prophage. The mutated phage replication gene was closely related to a virulence marker identified in recently emerged M3 serotype S. pyogenes strains in Japan. This observation suggests that prophage genes confer selective advantage to the lysogenic host. SF370.3 encodes a hyaluronidase and a DNase that may facilitate the spreading of S. pyogenes through tissue planes of its human host. Prophage SF370.2 showed a 43-kb-long genome that closely resembled the genome organization of pac-site temperate Siphoviridae infecting the dairy bacteria S. thermophilus and L. lactis. Over part of the structural genes, the similarity between SF370.2 and S. thermophilus phage O1205 extended to the nucleotide sequence level. SF370.2 showed two probable inactivating mutations: one in the replisome organizer gene and another in the gene encoding the portal protein. Prophage SF370.2 also encodes a hyaluronidase and in addition two very likely virulence factors: prophage-encoded toxins acting as superantigens that may contribute to the immune deregulation observed during invasive streptococcal infections. The superantigens are encoded between the phage lysin and the right attachment site of the prophage genome. The genes were nearly sequence identical with a DNA segment in S. equi, suggesting horizontal gene transfer. The trend for prophage genome inactivation was even more evident for the remaining five prophage sequences that showed massive losses of prophage DNA. In these prophage remnants only 13-0.3 kb of putative prophage DNA was detected. We discuss the genomics data from S. pyogenes strain SF370 within the framework of Darwinian coevolution of prophages and lysogenic bacteria and suggest elements of genetic cooperation and elements of an arms race in this host-parasite relationship.

Bacteriophages↗

PubMed2005

Coronavirus genome structure and replication.

In addition to the SARS coronavirus (treated separately elsewhere in this volume), the complete genome sequences of six species in the coronavirus genus of the coronavirus family [avian infectious bronchitis virus-Beaudette strain (IBV-Beaudette), bovine coronavirus-ENT strain (BCoV-ENT), human coronavirus-229E strain (HCoV-229E), murine hepatitis virus-A59 strain (MHV-A59), porcine transmissible gastroenteritis-Purdue 115 strain (TGEV-Purdue 115), and porcine epidemic diarrhea virus-CV777 strain (PEDV-CV777)] have now been reported. Their lengths range from 27,317 nt for HCoV-229E to 31,357 nt for the murine hepatitis virus-A59, establishing the coronavirus genome as the largest known among RNA viruses. The basic organization of the coronavirus genome is shared with other members of the Nidovirus order (the torovirus genus, also in the family Coronaviridae, and members of the family Arteriviridae) in that the nonstructural proteins involved in proteolytic processing, genome replication, and subgenomic mRNA synthesis (transcription) (an estimated 14-16 end products for coronaviruses) are encoded within the 5'-proximal two-thirds of the genome on gene 1 and the (mostly) structural proteins are encoded within the 3'-proximal one-third of the genome (8-9 genes for coronaviruses). Genes for the major structural proteins in all coronaviruses occur in the 5' to 3' order as S, E, M, and N. The precise strategy used by coronaviruses for genome replication is not yet known, but many features have been established. This chapter focuses on some of the known features and presents some current questions regarding genome replication strategy, the cis-acting elements necessary for genome replication [as inferred from defective interfering (DI) RNA molecules], the minimum sequence requirements for autonomous replication of an RNA replicon, and the importance of gene order in genome replication.

Animals↗

PubMed1997

Genome plasticity as a paradigm of eubacteria evolution.

To test the hypotheses that eubacterial genomes leave evolutionarily stable structures and that the variety of genome size is brought about through genome doubling during evolution, the genome structures of Haemophilus influenzae, Mycoplasma genitalium, Escherichia coli, and Bacillus subtilis were compared using the DNA sequences of the entire genome or substantial portions of genome. In these comparisons, the locations of orthologous genes were examined among different genomes. Using orthologous genes for the comparisons guaranteed that differences revealed in physical location would reflect changes in genome structure after speciation. We found that dynamic rearrangements have so frequently occurred in eubacterial genomes as to break operon structures during evolution, even after the relatively recent divergence between E. coli and H. influenzae. Interestingly, in such eubacterial genomes of high plasticity, we could find several highly conservative regions with the longest conserved region comprising the S10, spc, and alpha operons. This suggests that such exceptional conservative regions have undergone strong structural constraints during evolution.

Bacteria↗

PubMed2006

Analysis of papaya BAC end sequences reveals first insights into the organization of a fruit tree genome.

Papaya (Carica papaya L.) is a major tree fruit crop of tropical and subtropical regions with an estimated genome size of 372 Mbp. We present the analysis of 4.7% of the papaya genome based on BAC end sequences (BESs) representing 17 million high-quality bases. Microsatellites discovered in 5,452 BESs and flanking primer sequences are available to papaya breeding programs at http://www.genomics.hawaii.edu/papaya/BES . Sixteen percent of BESs contain plant repeat elements, the vast majority (83.3%) of which are class I retrotransposons. Several novel papaya-specific repeats were identified. Approximately 19.1% of the BESs have homology to Arabidopsis cDNA. Increasing numbers of completely sequenced plant genomes and BES projects enable novel approaches to comparative plant genomics. Paired BESs of Carica, Arabidopsis, Populus, Brassica and Lycopersicon were mapped onto the completed genomes of Arabidopsis and Populus. In general the level of microsynteny was highest between closely related organisms. However, papaya revealed a higher degree of apparent synteny with the more distantly related poplar than with the more closely related Arabidopsis. This, as well as significant colinearity observed between peach and poplar genome sequences, support recent observations of frequent genome rearrangements in the Arabidopsis lineage and suggest that the poplar genome sequence may be more useful for elucidating the papaya and other rosid genomes. These insights will play a critical role in selecting species and sequencing strategies that will optimally represent crop genomes in sequence databases.

Carica↗

PubMed2000

Genomic organization of Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus.

The genome organization of the Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus (HearNPV) was investigated and compared to that of other baculoviruses. A detailed physical map was constructed for the restriction enzymes BamHI, BglII, EcoRI, HindIII, KpnI, PstI, SacI and XhoI. The 130.1-kilobase pairs (kb) long viral genome was cloned as restriction fragments into a plasmid library, which covered 97.5% of the viral genome. From this plasmid library about 45 kb of dispersed sequence information was generated. Fifty-three putative open reading frames (ORFs) with homology to ORFs of other baculoviruses were identified and their location on the genome of HearNPV was determined. The arrangement of the ORFs along the HearNPV genome is significantly different from the multiple-nucleocapsid NPVs, AcMNPV, BmNPV and OpMNPV, which have a highly collinear genome, and the granulovirus XcGV. In contrast the genomes of HearNPV and SeMNPV are highly collinear. This close relatedness between an MNPV and an SNPV is supported by the phylogeny of specific genes of these two viruses and suggests that the morphotype (S or M) is only a taxonomic and not a phylogenetic denominator. The data presented here also give further support to the view that the gene distribution along baculovirus genomes can be used as a character to describe baculovirus relatedness independent of gene phylogeny. Five homologous regions (hrs) were located on the genome of HearNPV. This is also the first report of the existence of hrs in SNPVs and this observation suggests that hrs are a common feature of baculovirus genomes.

Animals↗

PubMed2004

Comparative DNA sequence analysis of mapped wheat ESTs reveals the complexity of genome relationships between rice and wheat.

The use of DNA sequence-based comparative genomics for evolutionary studies and for transferring information from model species to related large-genome species has revolutionized molecular genetics and breeding strategies for improving those crops. Comparative sequence analysis methods can be used to cross-reference genes between species maps, enhance the resolution of comparative maps, study patterns of gene evolution, identify conserved regions of the genomes, and facilitate interspecies gene cloning. In this study, 5,780 Triticeae ESTs that have been physically mapped using wheat ( Triticum aestivum L.) deletion lines and segregating populations were compared using NCBI BLASTN to the first draft of the public rice ( Oryza sativa L.) genome sequence data from 3,280 ordered BAC/PAC clones. A rice genome view of the homoeologous wheat genome locations based on sequence analysis shows general similarity to the previously published comparative maps based on Southern analysis of RFLP. For most rice chromosomes there is a preponderance of wheat genes from one or two wheat chromosomes. The physical locations of non-conserved regions were not consistent across rice chromosomes. Some wheat ESTs with multiple wheat genome locations are associated with the non-conserved regions of similarity between rice and wheat. The inverse view, showing the relationship between the wheat deletion map and rice genomic sequence, revealed the breakdown of gene content and order at the resolution conferred by the physical chromosome deletions in the wheat genome. An average of 35% of the putative single copy genes that were mapped to the most conserved bins matched rice chromosomes other than the one that was most similar. This suggests that there has been an abundance of rearrangements, insertions, deletions, and duplications eroding the wheat-rice genome relationship that may complicate the use of rice as a model for cross-species transfer of information in non-conserved regions.

Chromosome Mapping↗

PubMed2006

Evolution of genome size in fishes: a phylogenetic test of the Hinegardner and Rosen hypothesis.

Despite remarkable advances in genomic studies over the past few decades, surprisingly little is known about the processes governing genome evolution at macroevolutionary timescales. In a seminal paper, Hinegardner and Rosen (Am Nat 106:621-644, 1972) suggested that taxa characterized by larger genomes should also display disproportionately stronger fluctuations in genome size. Therefore, according to the Hinegardner and Rosen (HR) hypothesis, there should be a negative correlation between average within-family genome size and its corresponding coefficient of variation (CV), a prediction that was supported by their analysis of the genomes of 275 species of fish. In this study we reevaluate the HR hypothesis using an expanded dataset (2050 genome size records). Moreover, in addition to the use of standard linear regression techniques, we also conducted modern comparative analyses that take into account phylogenetic non-independence. Our analyses failed to confirm the negative relationship detected in the original study, suggesting that the evolution of genome size in fishes might be more complex than envisioned by the HR hypothesis. Interestingly, the frequency distribution of fish genome sizes was strongly skewed, even on a logarithmic scale, suggesting that the dynamics underlying genome size evolution are driven by multiplicative phenomena, which might include chromosomal rearrangements and the expansion of transposable elements.

Animals↗

PubMed2005

Ancestral state reconstructions for genomes.

The recent expansion of phylogenetic analysis from the traditional field of molecular evolution, analyzing histories of genes, to the nascent field of "genomic evolution", analyzing histories of entire genomes, enables the construction of trees based on genome information, the quantification of the key processes that shape genome content and, ultimately, plausible parsimony reconstructions of ancestral genomes. Thus, when genomes are considered as phylogenetic characters, it is possible to reconstruct not only the history of species but also the ancestral states in terms of genome structure or function. In the future, we might be able to accurately reconstruct--or retrodict--a chain of events that led to the emergence of a specific genome sequence and, ultimately, to synthesize ancestral genomes at will, creating a "Jurassic database" of genomes.

Evolution, Molecular↗

PubMed2005

Comparative analysis of BAC and whole genome shotgun sequences from an Anopheles gambiae region related to Plasmodium encapsulation.

The only natural mechanism of malaria transmission in sub-Saharan Africa is the mosquito, generally Anopheles gambiae. Blocking malaria parasite transmission by stopping the development of Plasmodium in the insect vector would provide a useful alternative to the current methods of malaria control. Toward this end, it is important to understand the molecular basis of the malaria parasite refractory phenotype in An. gambiae mosquito strains. We have selected and sequenced six bacterial artificial chromosome (BAC) clones from the Pen-1 region that is the major quantitative trait locus involved in Plasmodium encapsulation. The sequence and the annotation of five overlapping BAC clones plus one adjacent, but not contiguous clone, totaling 585kb of genomic sequence from the centromeric end of the Pen-1 region of the PEST strain were compared to that of the genome sequence of the same strain produced by the whole genome shotgun technique. This project identified 23 putative mosquito genes plus putative copies of the retrotransposable elements BEL12 and TRANSIBN1_AG in the six BAC clones. Nineteen of the predicted genes are most similar to their Drosophila melanogaster homologs while one is more closely related to vertebrate genes. Comparison of these new BAC sequences plus previously published BAC sequences to the cognate region of the assembled genome sequence identified three retrotransposons present in one sequence version but not the other. One of these elements, Indy, has not been previously described. These observations provide evidence for the recent active transposition of these elements and demonstrate the plasticity of the Anopheles genome. The BAC sequences strongly support the public whole genome shotgun assembly and automatic annotation while also demonstrating the benefit of complementary genome sequences and of human curation. Importantly, the data demonstrate the differences in the genome sequence of an individual mosquito compared to that of a hypothetical, average genome sequence generated by whole genome shotgun assembly.

Amino Acid Sequence↗

PubMed2005

The sequence and phylogenetic analysis of avian reovirus genome segments M1, M2, and M3 encoding the minor core protein muA, the major outer capsid protein muB, and the nonstructural protein muNS.

The sequences and phylogenetic analyses of the M-class genome segments of 12 avian reovirus strains are described. The S1133 M1 genome segment is 2283 base pairs long, encoding a protein muA consisted of 732 amino acids. Each M2 or M3 genome segment of 12 avian reovirus strains is 2158 or 1996 base pairs long, respectively, encoding a protein muB or muNS consisted of 676 and 635 amino acids, respectively. The S1133 genome segment has the 5' GCUUUU terminal motif, but each M2 and M3 genome segment displays the 5' GCUUUUU terminal motif which is common to other known avian reovirus genome segments. The UCAUC 3'-terminal sequences of the M-class genome segments are shared by both avian and mammalian reoviruses. Noncoding regions of both 5'- and 3'-termini of the S1133 M1 genome segment consist of 12 and 72 nucleotides, respectively, those of each M2 genome segment consist of 29 and 98 nucleotides, respectively, and those of each M3 genome segment are 24 and 64 nucleotides, respectively. Analysis of the average degree of the M-class gene and the deduced mu-class protein sequence identities indicated that the M2 genes and the muB proteins have the greatest level of sequence divergence. Computer searches revealed that the muA possesses a sequence motif (NH(2)-Leu-Ala-Leu-Asp-Pro-Pro-Phe-COOH) (residues 458-464) indicative of N-6 adenine-specific DNA methylase. Examination of the muB amino acid sequences indicated that the cleavage site of muB into muBN and muBC is between positions 42 and 43 near the N-terminus of the protein, and this site is conserved for each protein. During in vitro treatment of virions with trypsin to yield infectious subviral particles, both the N-terminal fragment delta and the C-terminal fragment phi were shown to be generated. The site of trypsin cleavage was identified in the deduced amino acid sequence of muB by determining the amino-terminal sequences of phi proteins: between arginine 582 and glycine 583. The predicted length of delta generated from muBC is very similar to that of delta generated from mammalian reovirus mu1C. Taken together, protein muB is structurally, and probably functionally, similar to its mammalian homolog, mu1. In addition, two regions near the C-terminal and with a propensity to form alpha-helical coiled-coil structures as previously indicated are observed for each protein muB. Phylogenetic analysis of the M-class genes revealed that the predicted phylograms delineated 3 M1, 5 M2, and 2 M3 lineages, no correlation with serotype or pathotype of the viruses. The results also showed that M2 lineages I-V consist of a mixture of viruses from the M1 and M3 genes of lineages I-III, reflecting frequent reassortment of these genes among virus strains.

Amino Acid Sequence↗

PubMed2004

Schistosoma mansoni genome project: an update.

A schistosome genome project was initiated by the World Health Organization in 1994 with the notion that the best prospects for identifying new targets for drugs, vaccines, and diagnostic development lie in schistosome gene discovery, development of chromosome maps, whole genome sequencing and genome analysis. Schistosoma mansoni has a haploid genome of 270 Mb contained on 8 pairs of chromosomes. It is estimated that the S. mansoni genome contains between 15000 and 25000 genes. There are approximately 16689 ESTs obtained from diverse libraries representing different developmental stages of S. mansoni, deposited in the NCBI EST database. More than half of the deposited sequences correspond to genes of unknown function. Approximately 40-50% of the sequences form unique clusters, suggesting that approximately 20-25% of the total schistosome genes have been discovered. Efforts to develop low resolution chromosome maps are in progress. There is a genome sequencing program underway that will provide 3X sequence coverage of the S. mansoni genome that will result in approximately 95% gene discovery. The genomics era has provided the resources to usher in the era of functional genomics that will involve microarrays to focus on specific metabolic pathways, proteomics to identify relevant proteins and protein-protein interactions to understand critical parasite pathways. Functional genomics is expected to accelerate the development of control and treatment strategies for schistosomiasis.

Animals↗

PubMed2000

The genomes of Onchocerca volvulus.

Onchocerca volvulus, the filarial parasite that causes onchocerciasis or river blindness, contains three distinct genomes. These include the nuclear genome, the mitochondrial genome and the genome of an intracellular endosymbiont of the genus Wolbachia. The nuclear genome is roughly 1.5x10(8) bp in size, and is arranged on four chromosome pairs. Analysis of expressed sequence tags from different life-cycle stages has resulted in the identification of transcripts from roughly 4000 O. volvulus genes. Several of these transcripts are highly abundant, including those encoding collagen and cuticular proteins. Analysis of several gene sequences from O. volvulus suggests that the nuclear genes of O. volvulus are relatively compact and are interrupted relatively frequently by small introns. The intron-exon boundaries of these genes generally follow the GU-AG rule characteristic of the splice donor and acceptors of other vertebrate organisms. The nuclear genome also contains at least one repeated sequence family of a 150 bp repeat which is arranged in tandem arrays and appears subject to concerted evolution. The mitochondrial genome of O. volvulus is remarkably compact, only 13747 bp in size. Consistent with the small size of the genome, four gene pairs overlap, eight contain no intergenic regions and the remaining gene pairs are separated by small intergenic domains ranging from 1 to 46 bp. The protein-coding genes of the O. volvulus mitochondrial genome exhibit a striking codon bias, with 15/20 amino acids having a single codon preference greater than 70%. Intraspecific variation in both the nuclear and mitochondrial genomes appears to be quite limited, consistent with the hypothesis that O. volvulus has suffered a genetic bottleneck in the recent past.

Animals↗

PubMed2003

The complete nucleotide sequence, genome organization, and origin of human adenovirus type 11.

The complete DNA sequence and transcription map of human adenovirus type 11 are reported here. This is the first published sequence for a subgenera B human adenovirus and demonstrates a genome organization highly similar to those of other human adenoviruses. All of the genes from the early, intermediate, and late regions are present in the expected locations of the genome for a human adenovirus. The genome size is 34,794 bp in length and has a GC content of 48.9%. Sequence alignment with genomes of groups A (Ad12), C (Ad5), D (Ad17), E (Simian adenovirus 25), and F (Ad40) revealed homologies of 64, 54, 68, 75, and 52%, respectively. Detailed genomic analysis demonstrated that Ads 11 and 35 are highly conserved in all areas except the hexon hypervariable regions and fiber. Similarly, comparison of Ad11 with subgroup E SAV25 revealed poor homology between fibers but high homology in proteins encoded by all other areas of the genome. We propose an evolutionary model in which functional viruses can be reconstituted following fiber substitution from one serotype to another. According to this model either the Ad11 genome is a derivative of Ad35, from which the fiber was substituted with Ad7, or the Ad35 genome is the product of a fiber substitution from Ad21 into the Ad11 genome. This model also provides a possible explanation for the origin of group E Ads, which are evolutionarily derived from a group C fiber substitution into a group B genome.

Adenoviruses, Human↗

PubMed2003

The structures of bovine herpesvirus 1 virion and concatemeric DNA: implications for cleavage and packaging of herpesvirus genomes.

Herpesvirus genomes are often characterized by the presence of direct and inverted repeats that delineate their grouping into six structural classes. Class D genomes consist of a long (L) segment and a short (S) segment. The latter is flanked by large inverted repeats. DNA replication produces concatemers of head-to-tail linked genomes that are cleaved into unit genomes during the process of packaging DNA into capsids. Packaged class D genomes are an equimolar mixture of two isomers in which S is in either of two orientations, presumably a consequence of homologous recombination between the inverted repeats. The L segment remains predominantly fixed in a prototype (P) orientation; however, low levels of genomes having inverted L (I(L)) segments have been reported for some class D herpesviruses. Inefficient formation of class D I(L) genomes has been attributed to infrequent L segment inversion, but recent detection of frequent inverted L segments in equine herpesvirus 1 concatemers [Virology 229 (1997) 415-420] suggests that the defect may be at the level of cleavage and packaging rather than inversion. In this study, the structures of virion and concatemeric DNA of another class D herpesvirus, bovine herpesvirus 1, were determined. Virion DNA contained low levels of I(L) genomes, whereas concatemeric DNA contained significant amounts of L segments in both P and I(L) orientations. However, concatemeric termini exhibited a preponderance of L termini derived from P isomers which was comparable to the preponderance of P genomes found in virion DNA. Thus, the defect in formation of I(L) genomes appears to lie at the level of concatemer cleavage. These results have important implications for the mechanisms by which herpesvirus DNA cleavage and packaging occur.

Animals↗

PubMed2001

Non-genomic effects of glucocorticoids in the neural system. Evidence, mechanisms and implications.

Complementing the classical concept of genomic steroid actions, here we (i) review evidence showing that important neural effects of glucocorticoids are exerted by non-genomic mechanisms; (ii) describe known mechanisms that may underlie such effects; (iii) summarize the functions and implications of non-genomic mechanisms and (iv) outline future directions of research. The role of non-genomic mechanisms is to shape the response of the organism to challenges that require a substantial reorganization of neural and somatic functions and involve massive behavioral shifts. Non-genomic effects may (i) prepare the cell for subsequent glucocorticoid-induced genomic changes, (ii) bridge the gap between the early need of change and the delay in the expression of genomic effects and (iii) may induce specific changes that in some instances are opposite to those induced by genomic mechanisms. The latter can be explained by the fact that challenging situations require different responses in early (acute) and later (chronic) phases. Data show that non-genomic mechanisms of glucocorticoid action play a role in both pathological phenomena and the expression of ameliorative pharmacological effects. Non-genomic mechanisms that underlie many glucocorticoid-induced neural changes constitute a for long overlooked controlling factor. Despite the multitude and the variety of accumulated data, important questions remain to be answered.

Animals↗

PubMed2001

Detecting anomalous gene clusters and pathogenicity islands in diverse bacterial genomes.

A gene in a genome is defined as putative alien (pA) if its codon usage difference from the average gene exceeds a high threshold and codon usage differences from ribosomal protein genes, chaperone genes and protein-synthesis-processing factors are also high. pA gene clusters in bacterial genomes are relevant for detecting genomic islands (GIs), including pathogenicity islands (PAIs). Four other analyses appropriate to this task are G+C genome variation (the standard method); genomic signature divergences (dinucleotide bias); extremes of codon bias; and anomalies of amino acid usage. For example, the cagA domain of Helicobacter pylori is highly deviant in its genome signature and codon bias from the rest of the genome. Using these methods we can detect two potential PAIs in the Neisseria meningitidis genome, which contain hemagglutinin and/or hemolysin-related genes. Additionally, G+C variation and genome signature differences of the Mycobacterium tuberculosis genome indicate two pA gene clusters.

Bacteria↗