Phylogenetic detection of conserved gene clusters in microbial genomes

BACKGROUND: Microbial genomes contain an abundance of genes with conserved proximity forming clusters on the chromosome. However, the conservation can be a result of many factors such as vertical inheritance, or functional selection. Thus, identification of conserved gene clusters that are under functional selection provides an effective channel for gene annotation, microarray screening, and pathway reconstruction. The problem of devising a robust method to identify these conserved gene clusters and to evaluate the significance of the conservation in multiple genomes has a number of implications for comparative, evolutionary and functional genomics as well as synthetic biology. RESULTS: In this paper we describe a new method for detecting conserved gene clusters that incorporates the information captured by a genome phylogenetic tree. We show that our method can overcome the common problem of overestimation of significance due to the bias in the genome database and thereby achieve better accuracy when detecting functionally connected gene clusters. Our results can be accessed at database GeneChords . CONCLUSION: The methodology described in this paper gives a scalable framework for discovering conserved gene clusters in microbial genomes. It serves as a platform for many other functional genomic analyses in microorganisms, such as operon prediction, regulatory site prediction, functional annotation of genes, evolutionary origin and development of gene clusters

Analysis of 1,000+ Type-Strain Genomes Substantially Improves Taxonomic Classification of Alphaproteobacteria.

The class Alphaproteobacteria is comprised of a diverse assemblage of Gram-negative bacteria that includes organisms of varying morphologies, physiologies and habitat preferences many of which are of clinical and ecological importance. Alphaproteobacteria classification has proved to be difficult, not least when taxonomic decisions rested heavily on a limited number of phenotypic features and interpretation of poorly resolved 16S rRNA gene trees. Despite progress in recent years regarding the classification of bacteria assigned to the class, there remains a need to further clarify taxonomic relationships. Here, draft genome sequences of a collection of genomes of more than 1000 Alphaproteobacteria and outgroup type strains were used to infer phylogenetic trees from genome-scale data using the principles drawn from phylogenetic systematics. The majority of taxa were found to be monophyletic but several orders, families and genera, including taxa recognized as problematic long ago but also quite recent taxa, as well as a few species were shown to be in need of revision. According proposals are made for the recognition of new orders, families and genera, as well as the transfer of a variety of species to other genera and of a variety of genera to other families. In addition, emended descriptions are given for many species mainly involving information on DNA G+C content and (approximate) genome size, both of which are confirmed as valuable taxonomic markers. Similarly, analysis of the gene content was shown to provide valuable taxonomic insights in the class. Significant incongruities between 16S rRNA gene and whole genome trees were not found in the class. The incongruities that became obvious when comparing the results of the present study with existing classifications appeared to be caused mainly by insufficiently resolved 16S rRNA gene trees or incomplete taxon sampling. Another probable cause of misclassifications in the past is the partially low overall fit of phenotypic characters to the sequence-based tree. Even though a significant degree of phylogenetic conservation was detected in all characters investigated, the overall fit to the tree varied considerably

Genome Sequences and Methylation Patterns of Natrinema versiforme BOL5-4 and Natrinema pallidum BOL6-1, Two Extremely Halophilic Archaea from a Bolivian Salt Mine

Two extremely halophilic archaea, namely, Natrinema versiforme BOL5-4 and Natrinema pallidum BOL6-1, were isolated from a Bolivian salt mine and their genomes sequenced using single-molecule real-time sequencing. The GC-rich genomes of BOL5-4 and BOL6-1 were 4.6 and 3.8 Mbp, respectively, with large chromosomes and multiple megaplasmids. Genome annotation was incorporated into HaloWeb and methylation patterns incorporated into REBASE.Fil: DasSarma, Priya. University of Maryland; Estados UnidosFil: Anton, Brian P.. New England BioLabs; Estados UnidosFil: DasSarma, Satyajit L.. University of Maryland; Estados UnidosFil: Martínez, Fabiana Lilian. University of Maryland; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones para la Industria Química. Universidad Nacional de Salta. Facultad de Ingeniería. Instituto de Investigaciones para la Industria Química; ArgentinaFil: Guzman, Daniel. Universidad Mayor de San Simón; BoliviaFil: Roberts, Richard J.. New England BioLabs; Estados UnidosFil: DasSarma, Shiladitya. University of Maryland; Estados Unido

Unraveling the genomic mosaic of a ubiquitous genus of marine cyanobacteria

Background: The picocyanobacterial genus Synechococcus occurs over wide oceanic expanses, having colonized most available niches in the photic zone. Large scale distribution patterns of the different Synechococcus clades (based on 16S rRNA gene markers) suggest the occurrence of two major lifestyles ('opportunists'/'specialists'), corresponding to two distinct broad habitats ('coastal'/'open ocean'). Yet, the genetic basis of niche partitioning is still poorly understood in this ecologically important group. Results: Here, we compare the genomes of 11 marine Synechococcus isolates, representing 10 distinct lineages. Phylogenies inferred from the core genome allowed us to refine the taxonomic relationships between clades by revealing a clear dichotomy within the main subcluster, reminiscent of the two aforementioned lifestyles. Genome size is strongly correlated with the cumulative lengths of hypervariable regions (or 'islands'). One of these, encompassing most genes encoding the light-harvesting phycobilisome rod complexes, is involved in adaptation to changes in light quality and has clearly been transferred between members of different Synechococcus lineages. Furthermore, we observed that two strains (RS9917 and WH5701) that have similar pigmentation and physiology have an unusually high number of genes in common, given their phylogenetic distance. Conclusion: We propose that while members of a given marine Synechococcus lineage may have the same broad geographical distribution, local niche occupancy is facilitated by lateral gene transfers, a process in which genomic islands play a key role as a repository for transferred genes. Our work also highlights the need for developing picocyanobacterial systematics based on genome-derived parameters combined with ecological and physiological data

Genome sequence of Salarchaeum sp. Strain JOR-1, an extremely halophilic archaeon from the Dead Sea

An extremely halophilic archaeon, Salarchaeum sp. strain JOR-1, was isolated from the east coast of the Dead Sea, Kingdom of Jordan, and sequenced using single-molecule real-time (SMRT) sequencing. The GC-rich 2.5-Mbp genome was composed of a circular chromosome and a megaplasmid. The genome contained 2,633 genes and was incorporated into HaloWeb.Fil: Anton, Brian P.. New England Biolabs; Estados UnidosFil: DasSarma, Priya. University of Maryland; Estados UnidosFil: Martínez, Fabiana Lilian. University of Maryland; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Universidad Nacional de Salta. Facultad de Ingeniería. Instituto Nacional de Investigaciones para las Industrias Químicas; ArgentinaFil: DasSarma, Satyajit L.. University of Maryland; Estados UnidosFil: Madadha, Mohammad Al. University of Jordan; Jordania. University of Maryland; Estados UnidosFil: Roberts, Richard J.. New England Biolabs; Estados UnidosFil: DasSarma, Shiladitya. University of Maryland; Estados Unido

Aurintricarboxylic Acid is a Canonical Disruptor of the TAZ-TEAD Transcriptional Complex

Disrupting the formation of the oncogenic YAP/TAZ-TEAD transcriptional complex holds substantial therapeutic potential. However, the three protein interaction interfaces of this complex cannot be easily disrupted using small molecules. Here, we report that the pharmacologically active small molecule aurintricarboxylic acid (ATA) acts as a disruptor of the TAZ-TEAD complex. ATA was identified in a high-throughput screen using a TAZ-TEAD AlphaLISA assay that was tailored to identify disruptors of this transcriptional complex. We further used fluorescence polarization assays both to confirm disruption of the TAZ-TEAD complex and to demonstrate that ATA binds to interface 3. We have previously shown that cell-based models that express the oncogenic TAZ-CAMTA1 (TC) fusion protein display enhanced TEAD transcriptional activity because TC functions as an activated form of TAZ. Utilizing cell-based studies and our TC model system, we performed TC/TEAD reporter, RNA-Seq, and qPCR assays and found that ATA inhibits TC/TEAD transcriptional activity. Further, disruption of TC/TEAD and TAZ/TEAD interaction by ATA abrogated anchorage-independent growth, the phenotype most closely linked to dysregulated TAZ/TEAD activity. Therefore, this study demonstrates that ATA is a novel small molecule that has the ability to disrupt the undruggable TAZ-TEAD interface

The Extended Blue Continuum and Line Emission around the Central Radio Galaxy in Abell 2597

We present results from detailed imaging of the centrally dominant radio elliptical galaxy in the cooling flow cluster Abell 2597, using data obtained with the Wide Field and Planetary Camera 2 (WFPC2) on the Hubble Space Telescope (HST). This object is one of the archetypal "blue-lobed" cooling flow radio elliptical galaxies, also displaying a luminous emission-line nebula, a compact radio source, and a significant dust lane and evidence of molecular gas in its center. We show that the radio source is surrounded by a complex network of emission-line filaments, some of which display a close spatial association with the outer boundary of the radio lobes. We present a detailed analysis of the physical properties of ionized and neutral gas associated with the radio lobes, and show that their properties are strongly suggestive of direct interactions between the radio plasma and ambient gas. We resolve the blue continuum emission into a series of knots and clumps, and present evidence that these are most likely due to regions of recent star formation. We investigate several possible triggering mechanisms for the star formation, including direct interactions with the radio source, filaments condensing from the cooling flow, or the result of an interaction with a gas-rich galaxy, which may also have been responsible for fueling the active nucleus. We propose that the properties of the source are plausibly explained in terms of accretion of gas by the cD during an interaction with a gas-rich galaxy, which combined with the fact that this object is located at the center of a dense, high-pressure ICM can account for the high rates of star formation and the strong confinement of the radio source.Comment: Astrophysical Journal, in press, 34 pages, includes 6 PostScript figures. Latex format, uses aaspp4.sty and epsf.sty file