Interplay of recombination and selection in the genomes of Chlamydia trachomatis

<p>Abstract</p> <p>Background</p> <p><it>Chlamydia trachomatis </it>is an obligate intracellular bacterial parasite, which causes several severe and debilitating diseases in humans. This study uses comparative genomic analyses of 12 complete published <it>C. trachomatis </it>genomes to assess the contribution of recombination and selection in this pathogen and to understand the major evolutionary forces acting on the genome of this bacterium.</p> <p>Results</p> <p>The conserved core genes of <it>C. trachomatis </it>are a large proportion of the pan-genome: we identified 836 core genes in <it>C. trachomatis </it>out of a range of 874-927 total genes in each genome. The ratio of recombination events compared to mutation (ρ/θ) was 0.07 based on ancestral reconstructions using the ClonalFrame tool, but recombination had a significant effect on genetic diversification (r/m = 0.71). The distance-dependent decay of linkage disequilibrium also indicated that <it>C. trachomatis </it>populations behaved intermediately between sexual and clonal extremes. Fifty-five genes were identified as having a history of recombination and 92 were under positive selection based on statistical tests. Twenty-three genes showed evidence of being under both positive selection and recombination, which included genes with a known role in virulence and pathogencity (e.g., <it>ompA, pmps, tarp</it>). Analysis of inter-clade recombination flux indicated non-uniform currents of recombination between clades, which suggests the possibility of spatial population structure in <it>C. trachomatis </it>infections.</p> <p>Conclusions</p> <p><it>C. trachomatis </it>is the archetype of a bacterial species where recombination is relatively frequent yet gene gains by horizontal gene transfer (HGT) and losses (by deletion) are rare. Gene conversion occurs at sites across the whole <it>C. trachomatis </it>genome but may be more often fixed in genes that are under diversifying selection. Furthermore, genome sequencing will reveal patterns of serotype specific gene exchange and selection that will generate important research questions for understanding <it>C. trachomatis </it>pathogenesis.</p> <p>Reviewers</p> <p>This article was reviewed by Dr. Jeremy Selengut, Dr. Lee S. Katz (nominated by Dr. I. King Jordan) and Dr. Arcady Mushegian.</p

The Bacillus anthracis chromosome contains four conserved, excision-proficient, putative prophages

BACKGROUND: Bacillus anthracis is considered to be a recently emerged clone within the Bacillus cereus sensu lato group. The B. anthracis genome sequence contains four putative lambdoid prophages. We undertook this study in order to understand whether the four prophages are unique to B. anthracis and whether they produce active phages. RESULTS: More than 300 geographically and temporally divergent isolates of B. anthracis and its near neighbors were screened by PCR for the presence of specific DNA sequences from each prophage region. Every isolate of B. anthracis screened by PCR was found to produce all four phage-specific amplicons whereas none of the non-B. anthracis isolates, produced more than one phage-specific amplicon. Excision of prophages could be detected by a PCR based assay for attP sites on extra-chromosomal phage circles and for attB sites on phage-excised chromosomes. SYBR-green real-time PCR assays indicated that prophage excision occurs at very low frequencies (2 × 10(-5 )- 8 × 10(-8)/cell). Induction with mitomycin C increased the frequency of excision of one of the prophages by approximately 250 fold. All four prophages appear to be defective since, mitomycin C induced culture did not release any viable phage particle or lyse the cells or reveal any phage particle under electron microscopic examination. CONCLUSION: The retention of all four putative prophage regions across all tested strains of B. anthracis is further evidence of the very recent emergence of this lineage and the prophage regions may be useful for differentiating the B. anthracis chromosome from that of its neighbors. All four prophages can excise at low frequencies, but are apparently defective in phage production

Microarray-based resequencing of multiple Bacillus anthracis isolates

We used custom-designed resequencing arrays to generate 3.1 Mb of genomic sequence from a panel of 56 Bacillus anthracis strains. Sequence quality was shown to be very high by replication (discrepancy rate of 7.4 × 10(-7)) and by comparison to independently generated shotgun sequence (discrepancy rate < 2.5 × 10(-6)). Population genomics studies of microbial pathogens using rapid resequencing technologies such as resequencing arrays are critical for recognizing newly emerging or genetically engineered strains

Finishing genomes with limited resources: lessons from an ensemble of microbial genomes

While new sequencing technologies have ushered in an era where microbial genomes can be easily sequenced, the goal of routinely producing high-quality draft and finished genomes in a cost-effective fashion has still remained elusive. Due to shorter read lengths and limitations in library construction protocols, shotgun sequencing and assembly based on these technologies often results in fragmented assemblies. Correspondingly, while draft assemblies can be obtained in days, finishing can take many months and hence the time and effort can only be justified for high-priority genomes and in large sequencing centers. In this work, we revisit this issue in light of our own experience in producing finished and nearly-finished genomes for a range of microbial species in a small-lab setting. These genomes were finished with surprisingly little investments in terms of time, computational effort and lab work, suggesting that the increased access to sequencing might also eventually lead to a greater proportion of finished genomes from small labs and genomics cores

The pH-responsive PacC transcription factor of Aspergillus fumigatus governs epithelial entry and tissue invasion during pulmonary aspergillosis

Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. Raw data have been deposited in the Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE54810. Funding: This work was supported in part by grants to EMB from the MRC (G0501164) and BBSRC (BB/G009619/1), to EMB and NDR from the Wellcome Trust (WT093596MA), to MB from Imperial College London (Division of Investigative Sciences PhD Studentship), to HH from the ERA-NET PathoGenoMics project TRANSPAT, Austrian Science Foundation (FWF I282-B09), to SGF from the National Institutes of Health, USA (R01AI073829). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Absorption-Line Probes of Gas and Dust in Galactic Superwinds

We discuss moderate resolution spectra of the NaD absorption-line in a sample of 32 far-IR-bright starburst galaxies. In 18 cases, the line is produced primarily by interstellar gas, and in 12 of these it is blueshifted by over 100 km/s relative to the galaxy systemic velocity. The absorption-line profiles in these outflow sources span the range from near the galaxy systemic velocity to a maximum blueshift of 400 to 600 km/s. The outflows occur in galaxies systematically viewed more nearly face-on than the others. We therefore argue that the absorbing material consists of ambient interstellar gas accelerated along the minor axis of the galaxy by a hot starburst-driven superwind. The NaD lines are optically-thick, but indirect arguments imply total Hydrogen column densities of N_H = few X 10^{21} cm^{-2}. This implies that the superwind is expelling matter at a rate comparable to the star-formation rate. This outflowing material is very dusty: we find a strong correlation between the depth of the NaD profile and the line-of-sight reddening (E(B-V) = 0.3 to 1 over regions several-to-ten kpc in size). The estimated terminal velocities of superwinds inferred from these data and extant X-ray data are typically 400 to 800 km/s, are independent of the galaxy rotation speed, and are comparable to (substantially exceed) the escape velocities for $L_*$ (dwarf) galaxies. The resulting loss of metals can establish the mass-metallicity relation in spheroids, produce the observed metallicity in the ICM, and enrich a general IGM to 10$^{-1}$ solar metallicity. If the outflowing dust grains survive their journey into the IGM, their effect on observations of cosmologically-distant objects is significant.Comment: 65 pages, including 16 figures. ApJ, in pres

DIYA: a bacterial annotation pipeline for any genomics lab

Summary:DIYA (Do-It-Yourself Annotator) is a modular and configurable open source pipeline software, written in Perl, used for the rapid annotation of bacterial genome sequences. The software is currently used to take DNA contigs as input, either in the form of complete genomes or the result of shotgun sequencing, and produce an annotated sequence in Genbank file format as output

Genomic characterization of the Yersinia genus

Comparative Yersinia genomics identifies features responsible for the colonization of specific host habitats and the horizontal transfer of virulence determinants

Conformation and dynamics of human urotensin II and urotensin related peptide in aqueous solution

Conformation and dynamics of the vasoconstrictive peptides human urotensin II (UII) and urotensin related peptide (URP) have been investigated by both unrestrained and enhanced-sampling molecular-dynamics (MD) simulations and NMR spectroscopy. These peptides are natural ligands of the G-protein coupled urotensin II receptor (UTR) and have been linked to mammalian pathophysiology. UII and URP cannot be characterized by a single structure but exist as an equilibrium of two main classes of ring conformations, <i>open</i> and <i>folded</i>, with rapidly interchanging subtypes. The <i>open</i> states are characterized by turns of various types centered at K⁸Y⁹ or F⁶W⁷ predominantly with no or only sparsely populated transannular hydrogen bonds. The <i>folded</i> conformations show multiple turns stabilized by highly populated transannular hydrogen bonds comprising centers F⁶W⁷K⁸ or W⁷K⁸Y⁹. Some of these conformations have not been characterized previously. The equilibrium populations that are experimentally difficult to access were estimated by replica-exchange MD simulations and validated by comparison of experimental NMR data with chemical shifts calculated with density-functional theory. UII exhibits approximately 72% <i>open</i>:28% <i>folded</i> conformations in aqueous solution. URP shows very similar ring conformations as UII but differs in an <i>open:folded</i> equilibrium shifted further toward <i>open</i> conformations (86:14) possibly arising from the absence of folded N-terminal tail-ring interaction. The results suggest that the different biological effects of UII and URP are not caused by differences in ring conformations but rather by different interactions with UTR