CiteULike: treangen's library [233 articles]

Adapting to environmental changes using specialized paralogs

Gabino Sanchez-Perez — 2008-07-11T14:32:40-00:00

Trends in Genetics, Vol. 24, No. 4. (April 2008), pp. 154-158.

When a bacterial species survives under changing environmental circumstances (e.g. salinity or temperature), its proteins might not function in all physicochemical conditions. We propose that prokaryotes cope with this problem by having two or more copies of the genes affected by environmental fluctuations, each one performing the same function under different conditions (i.e. ecoparalog). We identify potential examples in the bacterium Salinibacter ruber and in other species that experience wide environmental variations.

Improved hit criteria for DNA local alignment.

L Noé — 2006-05-11T05:20:10-00:00

BMC Bioinformatics, Vol. 5 (14 October 2004)

BACKGROUND: The hit criterion is a key component of heuristic local alignment algorithms. It specifies a class of patterns assumed to witness a potential similarity, and this choice is decisive for the selectivity and sensitivity of the whole method. RESULTS: In this paper, we propose two ways to improve the hit criterion. First, we define the group criterion combining the advantages of the single-seed and double-seed approaches used in existing algorithms. Second, we introduce transition-constrained seeds that extend spaced seeds by the possibility of distinguishing transition and transversion mismatches. We provide analytical data as well as experimental results, obtained with the YASS software, supporting both improvements. CONCLUSIONS: Proposed algorithmic ideas allow to obtain a significant gain in sensitivity of similarity search without increase in execution time. The method has been implemented in YASS software available at http://www.loria.fr/projects/YASS/.

The impact of the neisserial DNA uptake sequences on genome evolution and stability

Todd Treangen — 2008-03-26T23:35:38-00:00

Genome Biology, Vol. 9, No. 3. (2008)

BACKGROUND:We investigated the origin and distribution of the abundant short DNA uptake sequence (DUS) in six genomes of Neisseria, a naturally transformable group of human pathogens. DUS are required for efficient transformation and their distribution may reflect their evolutionary role and that of transformation itself. RESULTS:We made a multiple alignment of 6 neisserial genomes and found that DUS arise by recombination. The spacing of DUS in the chromosomes matches the average size of conversion fragments. This is taken as evidence that transformation and recombination are tightly linked in genome evolution and also that recombination plays a key role in the establishment of DUS. DUS are overrepresented in the core genome, under-represented in regions under selective pressure driving diversification and totally absent in both recently acquired genes and recently lost core genes. This further suggests that DUS are implicated in genome stability rather than in variation. The substitution patterns in the core genome show that DUS elements are located in permissive regions but are highly conserved, suggesting that they are in mutation-selection balance and/or fuelled by molecular drive. Preliminary analyses indicate that these results also apply to the functionally analogous uptake signal sequence (USS) in Pasteurellaceae. CONCLUSION:The distribution of DUS is best explained by its recombinogenic past. As many other pathogens, Neisseria and Pasteurellaceae have hyperdynamic genomes generating deleterious mutations by intra-chromosomal recombination and by transient hypermutation. The results presented here suggest that transformation in Neisseria and Pasteurellaceae allows counteracting the deleterious effects of genome instability in the core genome. Thus, rather than promoting hypervariation, bacterial sex could be regenerative.

PSAT: A web tool to compare genomic neighborhoods of multiple prokaryotic genomes

Christine Fong — 2008-03-26T23:49:30-00:00

BMC Bioinformatics, Vol. 9, No. 1. (2008)

BACKGROUND:The conservation of gene order among prokaryotic genomes can provide valuable insight into gene function, protein interactions, or events by which genomes have evolved. Although some tools are available for visualizing and comparing the order of genes between genomes of study, few support an efficient and organized analysis between large numbers of genomes. The Prokaryotic Sequence homology Analysis Tool (PSAT) is a web tool for comparing gene neighborhoods among multiple prokaryotic genomes.RESULTS:PSAT utilizes a database that is preloaded with gene annotation, BLAST hit results, and gene-clustering scores designed to help identify regions of conserved gene order. Researchers use the PSAT web interface to find a gene of interest in a reference genome and efficiently retrieve the sequence homologs found in other bacterial genomes. The tool generates a graphic of the genomic neighborhood surrounding the selected gene and the corresponding regions for its homologs in each comparison genome. Homologs in each region are color coded to assist users with analyzing gene order among various genomes. In contrast to common comparative analysis methods that filter sequence homolog data based on alignment score cutoffs, PSAT leverages gene context information for homologs, including those with weak alignment scores, enabling a more sensitive analysis. Features for constraining or ordering results are designed to help researchers browse results from large numbers of comparison genomes in an organized manner. PSAT has been demonstrated to be useful for helping to identify gene orthologs and potential functional gene clusters, and detecting genome modifications that may result in loss of function.CONCLUSIONS:PSAT allows researchers to investigate the order of genes within local genomic neighborhoods of multiple genomes. A PSAT web server for public use is available for performing analyses on a growing set of reference genomes through any web browser with no client side software setup or installation required. Source code is freely available to researchers interested in setting up a local version of PSAT for analysis of genomes not available through the public server. Access to the public web server and instructions for obtaining source code can be found at http://www.nwrce.org/psat.

Comparative genome assembly.

M Pop — 2007-03-07T04:40:34-00:00

Brief Bioinform, Vol. 5, No. 3. (September 2004), pp. 237-248.

One of the most complex and computationally intensive tasks of genome sequence analysis is genome assembly. Even today, few centres have the resources, in both software and hardware, to assemble a genome from the thousands or millions of individual sequences generated in a whole-genome shotgun sequencing project. With the rapid growth in the number of sequenced genomes has come an increase in the number of organisms for which two or more closely related species have been sequenced. This has created the possibility of building a comparative genome assembly algorithm, which can assemble a newly sequenced genome by mapping it onto a reference genome. We describe here a novel algorithm for comparative genome assembly that can accurately assemble a typical bacterial genome in less than four minutes on a standard desktop computer. The software is available as part of the open-source AMOS project.

Mind the gaps: Progress in progressive alignment

DG Higgins — 2008-02-12T06:54:35-00:00

Proceedings of the National Academy of Sciences, Vol. 102, No. 30. (26 July 2005), pp. 10411-10412.

10.1073/pnas.0504801102

Multiple spaced seeds for homology search.

Lucian Ilie — 2007-11-17T02:40:25-00:00

Bioinformatics (5 September 2007)

MOTIVATION: Homology search finds similar segments between two biological sequences, such as DNA or protein sequences. The introduction of optimal spaced seeds in PatternHunter, (Ma et al., 2002), has increased both the sensitivity and the speed of homology search and it has been adopted by many alignment programs such as BLAST. With the further improvement provided by multiple spaced seeds in PatternHunterII, (Li et al., 2004), Smith-Waterman sensitivity is approached at BLASTn speed. However, computing optimal multiple spaced seeds was proved to be NP-hard and current heuristic algorithms are all very slow (exponential). RESULTS: We give a simple algorithm which computes good multiple seeds in polynomial time. Due to a completely different approach, the difference with respect to the previous methods is dramatic. The multiple spaced seed of PatternHunterII, with 16 weight 11 seeds, (Li et al., 2004), was computed in 12 days. It takes us 17 seconds to find a better one. Our approach changes the way of looking at multiple spaced seeds. CONTACT: ilie@csd.uwo.ca.

Patternhunter II: highly sensitive and fast homology search.

M Li — 2008-02-10T22:58:17-00:00

J Bioinform Comput Biol, Vol. 2, No. 3. (September 2004), pp. 417-439.

Extending the single optimized spaced seed of PatternHunter(20) to multiple ones, PatternHunter II simultaneously remedies the lack of sensitivity of Blastn and the lack of speed of Smith-Waterman, for homology search. At Blastn speed, PatternHunter II approaches Smith-Waterman sensitivity, bringing homology search methodology research back to a full circle.

The Maintenance of Sex in Bacteria Is Ensured by Its Potential to Reload Genes

Gergely Szollosi — 2008-02-09T11:58:50-00:00

Genetics, Vol. 174, No. 4. (1 December 2006), pp. 2173-2180.

Why sex is maintained in nature is a fundamental question in biology. Natural genetic transformation (NGT) is a sexual process by which bacteria actively take up exogenous DNA and use it to replace homologous chromosomal sequences. As it has been demonstrated, the role of NGT in repairing deleterious mutations under constant selection is insufficient for its survival, and the lack of other viable explanations have left no alternative except that DNA uptake provides nucleotides for food. Here we develop a novel simulation approach for the long-term dynamics of genome organization (involving the loss and acquisition of genes) in a bacterial species consisting of a large number of spatially distinct populations subject to independently fluctuating ecological conditions. Our results show that in the presence of weak interpopulation migration NGT is able to subsist as a mechanism to reload locally lost, intermittently selected genes from the collective gene pool of the species through DNA uptake from migrants. Reloading genes and combining them with those in locally adapted genomes allow individual cells to readapt faster to environmental changes. The machinery of transformation survives under a wide range of model parameters readily encompassing real-world biological conditions. These findings imply that the primary role of NGT is not to serve the cell with food, but to provide homologous sequences for restoring genes that have disappeared from or become degraded in the local population. 10.1534/genetics.106.063412

Interference among deleterious mutations favours sex and recombination in finite populations

Peter Keightley — 2006-09-07T05:09:32-00:00

Nature, Vol. 443, No. 7107., pp. 89-92.

Evolution of Natural Transformation: Testing the DNA Repair Hypothesis in Bacillus subtilis and Haemophilus influenzae

RJ Redfield — 2008-02-09T11:56:11-00:00

Genetics, Vol. 133, No. 4. (1 April 1993), pp. 755-761.

DNA Repair and the Evolution of Transformation in Haemophilus influenzae

JA Mongold — 2008-02-09T11:53:19-00:00

Genetics, Vol. 132, No. 4. (1 December 1992), pp. 893-898.

Transformation Proteins and DNA Uptake Localize to the Cell Poles in Bacillus subtilis

Jeanette Hahn — 2008-02-09T11:51:43-00:00

Cell, Vol. 122, No. 1. (15 July 2005), pp. 59-71.

Summary The Gram-positive, rod-forming bacterium Bacillus subtilis efficiently binds and internalizes transforming DNA. The localization of several competence proteins, required for DNA uptake, has been studied using fluorescence microscopy. At least three proteins (ComGA, ComFA, and YwpH) are preferentially associated with the cell poles and appear to colocalize. This association is dynamic; the proteins accumulate at the poles as transformability develops and then delocalize as transformability wanes. DNA binding and uptake also occur preferentially at the cell poles, as shown using fluorescent DNA and in single-molecule experiments with laser tweezers. In addition to the prominent polar sites, the competence proteins also localize as foci in association with the lateral cell membrane, but this distribution does not exhibit the same temporal changes as the polar accumulation. The results suggest the regulated assembly and disassembly of a DNA-uptake machine at the cell poles.

Intracellular protein and DNA dynamics in competent Bacillus subtilis cells.

D Kidane — 2006-08-06T00:45:36-00:00

Cell, Vol. 122, No. 1. (15 July 2005), pp. 73-84.

We have found that two DNA repair/recombination proteins localize differentially to the cell poles in competent Bacillus subtilis cells. RecA protein colocalized with competence protein ComGA, and its polar localization largely depended on ComGA and ComK activity, while RecN oscillated between the poles in a minute time frame, independent of any competence factor. Oscillation of RecN arrested upon addition of external DNA, suggesting that an interaction with incoming single-stranded (ss) DNA favors the localization of RecN at the pole containing the competence machinery. In agreement with this model, purified RecN protein showed ATP-dependent binding to ssDNA. Addition of DNA resulted in the formation of RecA threads emanating from the competence machinery. Our data show that in competent bacteria there exists a specifically positioned and dynamic ssDNA binding apparatus that accepts ssDNA taken up through the polar competence machinery and processes ssDNA for recombination with chromosomal DNA via extended RecA filaments.

DprA/Smf protein localizes at the DNA uptake machinery in competent Bacillus subtilis cells

Serkalem Tadesse — 2007-11-29T14:46:17-00:00

BMC Microbiology, Vol. 7 (28 November 2007), 105.

Plastic cells and populations: DNA substrate characteristics in Helicobacter pylori transformation define a flexible but conservative system for genomic variation.

SM Levine — 2007-12-03T16:13:40-00:00

FASEB J, Vol. 21, No. 13. (November 2007), pp. 3458-3467.

Helicobacter pylori, bacteria that colonize the human gastric mucosa, are naturally competent for transformation by exogenous DNA, and show a panmictic population structure. To understand the mechanisms involved in its horizontal gene transfer, we sought to define the interval required from exposure to substrate DNA until DNA uptake and expression of a selectable phenotype, as well as the relationship of transforming fragment length, concentration, homology, symmetry, and strandedness, to the transformation frequency. We provide evidence that natural transformation in H. pylori differs in efficiency among wild-type strains but is saturable and varies with substrate DNA length, symmetry, strandedness, and species origin. We show that H. pylori cells can be transformed within one minute of contact with DNA, by DNA fragments as small as 50 bp, and as few as 5 bp on one flank of a selectable single nucleotide mutation is sufficient substrate for recombination of a transforming fragment, and that double-stranded DNA is the preferred (1000-fold >single-stranded) substrate. The high efficiency of double-stranded DNA as transformation substrate, in conjunction with strain-specific restriction endonucleases suggests a model of short-fragment recombination favoring closest relatives, consistent with the observed H. pylori population biology.

From The Cover: Competence-programmed predation of noncompetent cells in the human pathogen Streptococcus pneumoniae: Genetic requirements

Sebastien Guiral — 2008-02-09T11:41:49-00:00

Proceedings of the National Academy of Sciences, Vol. 102, No. 24. (14 June 2005), pp. 8710-8715.

Natural competence for genetic transformation is the best-characterized feature of the major human pathogen Streptococcus pneumoniae. Recent studies have shown the virulence of competence-deficient mutants to be attenuated, but the nature of the connection between competence and virulence remained unknown. Here we document the release, triggered by competent cells, of virulence factors (e.g., the cytolytic toxin pneumolysin) from noncompetent cells. This phenomenon, which we name allolysis, involves a previously undescribed bacteriocin system consisting of a two-peptide bacteriocin, CibAB, and its immunity factor, CibC; the major autolysin, LytA, and lysozyme, LytC; and a proposed new amidase, CbpD. We show that CibAB are absolutely required for allolysis, whereas LytA and LytC can be supplied either by the competent cells or by the targeted cells. We propose that allolysis constitutes a competence-programmed mechanism of predation of noncompetent cells, which benefits to the competent cells and contributes to virulence by coordinating the release of virulence factors. 10.1073/pnas.0500879102

Competence-Induced Cells of Streptococcus pneumoniae Lyse Competence-Deficient Cells of the Same Strain during Cocultivation

Hilde Steinmoen — 2008-02-09T11:40:25-00:00

J. Bacteriol., Vol. 185, No. 24. (15 December 2003), pp. 7176-7183.

Several streptococcal species are able to take up naked DNA from the environment and integrate it into their genomes by homologous recombination. This process is called natural transformation. In Streptococcus pneumoniae and related streptococcal species, competence for natural transformation is induced by a peptide pheromone through a quorum-sensing mechanism. Recently we showed that induction of the competent state initiates lysis and release of DNA from a subfraction of the bacterial population and that the efficiency of this process is influenced by cell density. Here we have further investigated the nature of this cell density-dependent release mechanism. Interestingly, we found that competence-induced pneumococci lysed competence-deficient cells of the same strain during cocultivation and that the efficiency of this heterolysis increased as the ratio of competent to noncompetent cells increased. Furthermore, our results indicate that the lysins made by competent pneumococci are not released into the growth medium. More likely, they are anchored to the surface of the competent cells by choline-binding domains and cause lysis of noncompetent pneumococci through cell-to-cell contact. 10.1128/JB.185.24.7176-7183.2003

Molecular and Biological Analysis of Eight Genetic Islands That Distinguish Neisseria meningitidis from the Closely Related Pathogen Neisseria gonorrhoeae

Silke Klee — 2008-02-09T11:28:12-00:00

Infect. Immun., Vol. 68, No. 4. (1 April 2000), pp. 2082-2095.

The pathogenic species Neisseria meningitidis and Neisseria gonorrhoeae cause dramatically different diseases despite strong relatedness at the genetic and biochemical levels. N. meningitidis can cross the blood-brain barrier to cause meningitis and has a propensity for toxic septicemia unlike N. gonorrhoeae. We previously used subtractive hybridization to identify DNA sequences which might encode functions specific to bacteremia and invasion of the meninges because they are specific to N. meningitidis and absent from N. gonorrhoeae. In this report we show that these sequences mark eight genetic islands that range in size from 1.8 to 40 kb and whose chromosomal location is constant. Five of these genetic islands were conserved within a representative set of strains and/or carried genes with homologies to known virulence factors in other species. These were deleted, and the mutants were tested for correlates of virulence in vitro and in vivo. This strategy identified one island, region 8, which is needed to induce bacteremia in an infant rat model of meningococcal infection. Region 8 encodes a putative siderophore receptor and a disulfide oxidoreductase. None of the deleted mutants was modified in its resistance to the bactericidal effect of serum. Neither were the mutant strains altered in their ability to interact with endothelial cells, suggesting that such interactions are not encoded by large genetic islands in N. meningitidis. 10.1128/IAI.68.4.2082-2095.2000

Acquired macrolide resistance genes and the 1 bp deletion in the mtrR promoter in Neisseria gonorrhoeae

Sydney Cousin — 2008-02-09T11:25:51-00:00

J. Antimicrob. Chemother., Vol. 51, No. 1. (1 January 2003), pp. 131-133.

The presence of macrolide-lincosamide-streptogramin B resistance genes erm(B), erm(C) and erm(F), the macrolide resistance mef(A) gene, and the DNA sequence of a 13 bp repeat in the promoter region of the mtrR gene, were determined in 62 Neisseria gonorrhoeae isolates collected between 1992 and 1999 in Seattle, Washington, USA. Eleven isolates with erythromycin and azithromycin MICs of [<=]0.06 mg/L, had no acquired genes or deletions in the 13 bp repeat region. Among 44 isolates with erythromycin MICs 1.0-16.0 mg/L, and azithromycin MICs 0.06-4.0 mg/L, 16 carried the 1 bp deletion in the mtrR promoter region alone, nine carried one or more of the four acquired macrolide resistance genes alone, and 14 carried both acquired macrolide resistance genes plus the 1 bp deletion in the mtrR promoter region. Three isolates with erythromycin MICs [>=] 8 mg/L, and azithromycin MICs of 4.0 mg/L, carried only erm genes. Five isolates with MICs of 1-2 mg/L did not carry the 1 bp deletion, or any of the acquired resistance genes examined. Our data suggest that the 1 bp deletion in the mtrR promoter region is not found in all erythromycin-resistant (MIC [>=] 1.0 mg/L) N. gonorrhoeae. 10.1093/jac/dkg040

A chromosomally integrated bacteriophage in invasive meningococci

Emmanuelle Bille — 2008-02-09T11:24:04-00:00

J. Exp. Med., Vol. 201, No. 12. (20 June 2005), pp. 1905-1913.

Cerebrospinal meningitis is a feared disease that can cause the death of a previously healthy individual within hours. Paradoxically, the causative agent, Neisseria meningitidis, is a common inhabitant of the human nasopharynx, and as such, may be considered a normal, commensal organism. Only in a small proportion of colonized people do the bacteria invade the bloodstream, from where they can cross the blood-brain barrier to cause meningitis. Furthermore, most meningococcal disease is caused by bacteria belonging to only a few of the phylogenetic groups among the large number that constitute the population structure of this genetically variable organism. However, the genetic basis for the differences in pathogenic potential remains elusive. By performing whole genome comparisons of a large collection of meningococcal isolates of defined pathogenic potential we brought to light a meningococcal prophage present in disease-causing bacteria. The phage, of the filamentous family, excises from the chromosome and is secreted from the bacteria via the type IV pilin secretin. Therefore, this element, by spreading among the population, may promote the development of new epidemic clones of N. meningitidis that are capable of breaking the normal commensal relationship with humans and causing invasive disease. 10.1084/jem.20050112

Microarray analysis of the Bacillus subtilis K-state: genome-wide expression changes dependent on ComK.

RM Berka — 2006-11-20T12:20:26-00:00

Mol Microbiol, Vol. 43, No. 5. (March 2002), pp. 1331-1345.

In Bacillus subtilis, the competence transcription factor ComK activates its own transcription as well as the transcription of genes that encode DNA transport proteins. ComK is expressed in about 10% of the cells in a culture grown to competence. Using DNA microarrays representing approximately 95% of the protein-coding open reading frames in B. subtilis, we compared the expression profiles of wild-type and comK strains, as well as of a mecA mutant (which produces active ComK in all the cells of the population) and a comK mecA double mutant. In these comparisons, we identified at least 165 genes that are upregulated by ComK and relatively few that are downregulated. The use of reporter fusions has confirmed these results for several genes. Many of the ComK-regulated genes are organized in clusters or operons, and 23 of these clusters are preceded by apparent ComK-box promoter motifs. In addition to those required for DNA uptake, other genes that are upregulated in the presence of ComK are probably involved in DNA repair and in the uptake and utilization of nutritional sources. From this and previous work, we conclude that the ComK regulon defines a growth-arrested state, distinct from sporulation, of which competence for genetic transformation is but one notable feature. We suggest that this is a unique adaptation to stress and that it be termed the 'K-state'.

Do bacteria have sex?

Rosemary Redfield — 2008-02-09T11:18:39-00:00

Nat Rev Genet, Vol. 2, No. 8. (2001), pp. 634-639.

Natural genetic exchange between Haemophilus and Neisseria: Intergeneric transfer of chromosomal genes between major human pathogens

Simon Kroll — 2006-04-10T17:58:52-00:00

PNAS, Vol. 95, No. 21. (13 October 1998), pp. 12381-12385.

10.1073/pnas.95.21.12381

Hypermutation in Pathogenic Bacteria: Frequent Phase Variation in Meningococci Is a Phenotypic Trait of a Specialized Mutator Biotype

Cecilia Bucci — 2008-02-09T11:12:12-00:00

Molecular Cell, Vol. 3, No. 4. (April 1999), pp. 435-445.

Expression of serogroup B meningococcal capsular polysaccharide undergoes frequent phase variation involving reversible frameshift mutations within a homopolymeric repeat in the siaD gene. A high rate of phase variation is the consequence of a biochemical defect in methyl-directed mismatch repair. The mutator phenotype is associated to the absence of DNA adenine methyltransferase (Dam) activity in all pathogenic isolates and in 50% of commensal strains. Analysis of the meningococcal dam gene region revealed that in all Dam- strains a gene encoding a putative restriction endonuclease (drg) that cleaves only the methylated DNA sequence 5'-GmeATC-3' replaced the dam gene. Insertional inactivation of the dam and/or drg genes indicated that high rates of phase variation and hypermutator phenotype are caused by absence of a functional dam gene.

DNA repair profiles of disease-associated isolates of Neisseria meningitidis.

T Davidsen — 2008-02-09T11:07:17-00:00

FEMS Immunol Med Microbiol, Vol. 49, No. 2. (March 2007), pp. 243-251.

Neisseria meningitidis, or the meningococcus, is the source of significant morbidity and mortality in humans worldwide. Even though mutability has been linked to the occurrence of outbreaks of epidemic disease, meningococcal DNA repair pathways are poorly delineated. For the first time, a collection of meningococcal disease-associated isolates has been demonstrated to express constitutively the DNA glycosylases MutY and Fpg in vivo. DNA sequence analysis showed considerable variability in the deduced amino acid sequences of MutS and Fpg, while MutY and RecA were highly conserved. Interestingly, multi-locus sequence typing demonstrated a putative link between the pattern of amino acid substitutions and levels of spontaneous mutagenicity in meningococcal strains. These results provide a basis for further studies aimed at resolving the genotype/phenotype relationships of meningococcal genome variability and mutator activity.

Mutator clones of Neisseria meningitidis in epidemic serogroup A disease

Anthony Richardson — 2008-02-09T11:05:45-00:00

Proceedings of the National Academy of Sciences, Vol. 99, No. 9. (30 April 2002), pp. 6103-6107.

Serogroup A Neisseria meningitidis has repeatedly caused widespread epidemics of meningitis and septicemia throughout the 20th century. Recently, in a limited collection of strains, epidemic serogroup A isolates were found to have elevated mutation rates that was caused by defects in mismatch repair pathways. To ascertain the role of these mutators in the epidemic spread of this serogroup, the prevalence of hypermutability in a collection of 95 serogroup A N. meningitidis invasive isolates was determined. Overall mutability in Neisseriae can be described by measuring both missense mutation rates as well as phase variation frequencies of "contingency loci." Fifty-seven percent of serogroup A isolates possessed elevated mutability, which could be divided into two classes: intermediate and high level. Eleven of 20 high-level mutators, with phase variation rates >100-fold higher than wild-type isolates, were defective in mismatch repair. Ten of the 34 intermediate mutators possessing >10-fold increases in phase variation rates could be partially complemented by a wild-type mutL allele. A high prevalence of mutators in epidemic isolates indicates that hypermutability may play a major role in the transmission of this pathogen. The added diversity derived from increased phase variation rates may allow fixation of mutator alleles more frequently during epidemic spread. 10.1073/pnas.092568699

Complete and variant forms of the 'gonococcal genetic island' in Neisseria meningitidis.

LA Snyder — 2008-02-09T11:01:19-00:00

Microbiology, Vol. 151, No. Pt 12. (December 2005), pp. 4005-4013.

Comparative genome hybridization using the pan-Neisseria microarray identified genes from the gonococcal genetic island (GGI) within Neisseria meningitidis strains of serogroups W-135, H, and Z. While some of these strains contain nearly all of the genes of the GGI, there are differences in the presence of some of these genes between the strains, including between those of the same serogroup. Attempts were then made to determine the location of the GGI in these meningococci. Sequencing of Neisseria gonorrhoeae strain MS11 revealed that the GGI is a conjugative plasmid that can be chromosomally integrated at the dif sites near ung and can also be present in its circularized form. In N. meningitidis, a dif site is present in this location and also serves as the point of chromosomal integration of the GGI in this species.

Neisseria gonorrhoeae secretes chromosomal DNA via a novel type IV secretion system

Holly Hamilton — 2005-03-05T00:07:05-00:00

Molecular Microbiology, Vol. 55, No. 6. (March 2005), pp. 1704-1721.

Rapid, accurate, computational discovery of Rho-independent transcription terminators illuminates their relationship to DNA uptake

Carleton Kingsford — 2007-02-22T18:48:09-00:00

Genome Biology, Vol. 8 (21 February 2007), R22.

Uncertainty in homology inferences: Assessing and improving genomic sequence alignment

Gerton Lunter — 2008-02-01T19:13:08-00:00

Genome Res., Vol. 18, No. 2. (1 February 2008), pp. 298-309.

Sequence alignment underpins all of comparative genomics, yet it remains an incompletely solved problem. In particular, the statistical uncertainty within inferred alignments is often disregarded, while parametric or phylogenetic inferences are considered meaningless without confidence estimates. Here, we report on a theoretical and simulation study of pairwise alignments of genomic DNA at humanmouse divergence. We find that >15% of aligned bases are incorrect in existing whole-genome alignments, and we identify three types of alignment error, each leading to systematic biases in all algorithms considered. Careful modeling of the evolutionary process improves alignment quality; however, these improvements are modest compared with the remaining alignment errors, even with exact knowledge of the evolutionary model, emphasizing the need for statistical approaches to account for uncertainty. We develop a new algorithm, Marginalized Posterior Decoding (MPD), which explicitly accounts for uncertainties, is less biased and more accurate than other algorithms we consider, and reduces the proportion of misaligned bases by a third compared with the best existing algorithm. To our knowledge, this is the first nonheuristic algorithm for DNA sequence alignment to show robust improvements over the classic NeedlemanWunsch algorithm. Despite this, considerable uncertainty remains even in the improved alignments. We conclude that a probabilistic treatment is essential, both to improve alignment quality and to quantify the remaining uncertainty. This is becoming increasingly relevant with the growing appreciation of the importance of noncoding DNA, whose study relies heavily on alignments. Alignment errors are inevitable, and should be considered when drawing conclusions from alignments. Software and alignments to assist researchers in doing this are provided at http://genserv.anat.ox.ac.uk/grape/. 10.1101/gr.6725608

Confidence in comparative genomics

Elliott Margulies — 2008-02-01T19:08:47-00:00

Genome Res., Vol. 18, No. 2. (1 February 2008), pp. 199-200.

10.1101/gr.7228008

Orthology, paralogy and proposed classification for paralog subtypes

Erik Sonnhammer — 2007-11-25T09:43:15-00:00

Trends in Genetics, Vol. 18, No. 12. (1 December 2002), pp. 619-620.

The construction of amino acid substitution matrices for the comparison of proteins with non-standard compositions

Yu Yi-Kuo — 2005-03-28T20:02:53-00:00

Bioinformatics, Vol. 21, No. 7. (01 April 2005), pp. 902-911.

The compositional adjustment of amino acid substitution matrices

Yi-Kuo Yu — 2008-02-04T15:52:43-00:00

Proceedings of the National Academy of Sciences, Vol. 100, No. 26. (23 December 2003), pp. 15688-15693.

Amino acid substitution matrices are central to protein-comparison methods. In most commonly used matrices, the substitution scores take a log-odds form, involving the ratio of "target" to "background" frequencies derived from large, carefully curated sets of protein alignments. However, such matrices often are used to compare protein sequences with amino acid compositions that differ markedly from the background frequencies used for the construction of the matrices. Of course, the target frequencies should be adjusted in such cases, but the lack of an appropriate way to do this has been a long-standing problem. This article shows that if one demands consistency between target and background frequencies, then a log-odds substitution matrix implies a unique set of target and background frequencies as well as a unique scale. Standard substitution matrices therefore are truly appropriate only for the comparison of proteins with standard amino acid composition. Accordingly, we present and evaluate a rationale for transforming the target frequencies implicit in a standard matrix to frequencies appropriate for a nonstandard context. This rationale yields asymmetric matrices for the comparison of proteins with divergent compositions. Earlier approaches are unable to deal with this case in a fully consistent manner. Composition-specific substitution matrix adjustment is shown to be of utility for comparing compositionally biased proteins, including those of organisms with nucleotide-biased, and therefore codon-biased, genomes or isochores. 10.1073/pnas.2533904100

Mobile elements: drivers of genome evolution.

HH Kazazian — 2007-01-08T16:12:37-00:00

Science, Vol. 303, No. 5664. (12 March 2004), pp. 1626-1632.

Mobile elements within genomes have driven genome evolution in diverse ways. Particularly in plants and mammals, retrotransposons have accumulated to constitute a large fraction of the genome and have shaped both genes and the entire genome. Although the host can often control their numbers, massive expansions of retrotransposons have been tolerated during evolution. Now mobile elements are becoming useful tools for learning more about genome evolution and gene function.

Construction of phylogenetic trees.

WM Fitch — 2008-01-31T14:40:46-00:00

Science, Vol. 155, No. 760. (20 January 1967), pp. 279-284.

Computer aids to protein sequence determination.

MO Dayhoff — 2008-01-31T14:39:28-00:00

J Theor Biol, Vol. 8, No. 1. (January 1965), pp. 97-112.

Complementary DNA sequencing: expressed sequence tags and human genome project

Md Adams — 2007-11-27T16:00:01-00:00

Science, Vol. 252, No. 5013. (21 June 1991), pp. 1651-1656.

Automated partial DNA sequencing was conducted on more than 600 randomly selected human brain complementary DNA (cDNA) clones to generate expressed sequence tags (ESTs). ESTs have applications in the discovery of new human genes, mapping of the human genome, and identification of coding regions in genomic sequences. Of the sequences generated, 337 represent new genes, including 48 with significant similarity to genes from other organisms, such as a yeast RNA polymerase II subunit; Drosophila kinesin, Notch, and Enhancer of split; and a murine tyrosine kinase receptor. Forty-six ESTs were mapped to chromosomes after amplification by the polymerase chain reaction. This fast approach to cDNA characterization will facilitate the tagging of most human genes in a few years at a fraction of the cost of complete genomic sequencing, provide new genetic markers, and serve as a resource in diverse biological research fields. 10.1126/science.2047873

Sequence analysis of phosphoserine-containing peptides. Modification for picomolar sensitivity.

HE Meyer — 2008-01-30T23:33:25-00:00

FEBS Lett, Vol. 204, No. 1. (11 August 1986), pp. 61-66.

Sequencing of phosphoserine-containing peptides yields normally no identifiable PTH-derivatives at those positions where phosphoserine is located. Here a new method is described which allows identification of the position of phosphoserine by chemical modification just before sequence analysis. In a one-step microbatch reaction, phosphoserine present in the intact peptide can be transformed quantitatively into stable derivatives such as beta-methylaminoalanine (MAA), S-ethanolcysteine or S-ethylcysteine. These derivatives are detectable during microsequencing with less than 100 pmol peptide using an Applied Biosystems gas-phase sequencer equipped with an on-line PTH amino acid analyzer.

Studies on polynucleotides. XCVI. Repair replications of short synthetic DNA's as catalyzed by DNA polymerases.

K Kleppe — 2008-01-30T23:27:47-00:00

J Mol Biol, Vol. 56, No. 2. (14 March 1971), pp. 341-361.

A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase.

F Sanger — 2008-01-30T23:20:48-00:00

J Mol Biol, Vol. 94, No. 3. (25 May 1975), pp. 441-448.

Molecules as documents of evolutionary history.

E Zuckerkandl — 2006-07-04T00:05:20-00:00

J Theor Biol, Vol. 8, No. 2. (March 1965), pp. 357-366.

Characteristics and stabilization of DNAase-sensitive protein synthesis in E. coli extracts.

JH MATTHAEI — 2008-01-30T23:17:13-00:00

Proc Natl Acad Sci U S A, Vol. 47 (15 October 1961), pp. 1580-1588.

The amide groups of insulin.

F SANGER — 2008-01-30T23:12:08-00:00

Biochem J, Vol. 59, No. 3. (March 1955), pp. 509-518.

Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid.

JD WATSON — 2006-11-15T23:34:45-00:00

Nature, Vol. 171, No. 4356. (25 April 1953), pp. 737-738.

Independent functions of viral protein and nucleic acid in growth of bacteriophage.

AD HERSHEY — 2008-01-30T23:05:33-00:00

J Gen Physiol, Vol. 36, No. 1. (May 1952), pp. 39-56.

ON THE CONFIGURATIONAL RELATIONSHIP OF 3-CHLOROBUTYRIC AND 3-HYDROXYBUTYRIC ACIDS.

P A Levene — 2008-01-30T22:59:13-00:00

Science, Vol. 69, No. 1776. (11 January 1929)

A THIRD GROUP OF LINKED GENES IN DROSOPHILA AMPELOPHILA.

A H Sturtevant — 2008-01-30T22:54:39-00:00

Science, Vol. 37, No. 965. (27 June 1913), pp. 990-992.

DAGchainer: a tool for mining segmental genome duplications and synteny

Brian Haas — 2004-12-28T18:22:26-00:00

Bioinformatics, Vol. 20, No. 18., 3643.