CHSMiner: a GUI tool to identify chromosomal homologous segments

<p>Abstract</p> <p>Background</p> <p>The identification of chromosomal homologous segments (CHS) within and between genomes is essential for comparative genomics. Various processes including insertion/deletion and inversion could cause the degeneration of CHSs.</p> <p>Results</p> <p>Here we present a Java software CHSMiner that detects CHSs based on shared gene content alone. It implements fast greedy search algorithm and rigorous statistical validation, and its friendly graphical interface allows interactive visualization of the results. We tested the software on both simulated and biological realistic data and compared its performance with similar existing software and data source.</p> <p>Conclusion</p> <p>CHSMiner is characterized by its integrated workflow, fast speed and convenient usage. It will be useful for both experimentalists and bioinformaticians interested in the structure and evolution of genomes.</p

i-ADHoRe 3.0—fast and sensitive detection of genomic homology in extremely large data sets

Comparative genomics is a powerful means to gain insight into the evolutionary processes that shape the genomes of related species. As the number of sequenced genomes increases, the development of software to perform accurate cross-species analyses becomes indispensable. However, many implementations that have the ability to compare multiple genomes exhibit unfavorable computational and memory requirements, limiting the number of genomes that can be analyzed in one run. Here, we present a software package to unveil genomic homology based on the identification of conservation of gene content and gene order (collinearity), i-ADHoRe 3.0, and its application to eukaryotic genomes. The use of efficient algorithms and support for parallel computing enable the analysis of large-scale data sets. Unlike other tools, i-ADHoRe can process the Ensembl data set, containing 49 species, in 1 h. Furthermore, the profile search is more sensitive to detect degenerate genomic homology than chaining pairwise collinearity information based on transitive homology. From ultra-conserved collinear regions between mammals and birds, by integrating coexpression information and protein–protein interactions, we identified more than 400 regions in the human genome showing significant functional coherence. The different algorithmical improvements ensure that i-ADHoRe 3.0 will remain a powerful tool to study genome evolution

The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis.

Synovial sarcomas are aggressive soft-tissue malignancies that express chromosomal translocation-generated fusion genes, SS18-SSX1 or SS18-SSX2 in most cases. Here, we report a mouse sarcoma model expressing SS18-SSX1, complementing our prior model expressing SS18-SSX2. Exome sequencing identified no recurrent secondary mutations in tumors of either genotype. Most of the few mutations identified in single tumors were present in genes that were minimally or not expressed in any of the tumors. Chromosome 6, either entirely or around the fusion gene expression locus, demonstrated a copy number gain in a majority of tumors of both genotypes. Thus, by fusion oncogene coding sequence alone, SS18-SSX1 and SS18-SSX2 can each drive comparable synovial sarcomagenesis, independent from other genetic drivers. SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences overall. In direct tumorigenesis comparisons, SS18-SSX2 was slightly more sarcomagenic than SS18-SSX1, but equivalent in its generation of biphasic histologic features. Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors. This suggests that the translocated locus may drive genotype-phenotype differences more than the coding sequence of the fusion gene created. Two possible roles for native SSX2 in synovial sarcomagenesis are explored. Thus, even specific partial failures of mouse genetic modeling can be instructive to human tumor biology

Mutations in the Lipopolysaccharide Biosynthesis Pathway Interfere with Crescentin-Mediated Cell Curvature in Caulobacter crescentus

Bacterial cell morphogenesis requires coordination among multiple cellular systems, including the bacterial cytoskeleton and the cell wall. In the vibrioid bacterium Caulobacter crescentus, the intermediate filament-like protein crescentin forms a cell envelope-associated cytoskeletal structure that controls cell wall growth to generate cell curvature. We undertook a genetic screen to find other cellular components important for cell curvature. Here we report that deletion of a gene (wbqL) involved in the lipopolysaccharide (LPS) biosynthesis pathway abolishes cell curvature. Loss of WbqL function leads to the accumulation of an aberrant Opolysaccharide species and to the release of the S layer in the culture medium. Epistasis and microscopy experiments show that neither S-layer nor O-polysaccharide production is required for curved cell morphology per se but that production of the altered O-polysaccharide species abolishes cell curvature by apparently interfering with the ability of the crescentin structure to associate with the cell envelope. Our data suggest that perturbations in a cellular pathway that is itself fully dispensable for cell curvature can cause a disruption of cell morphogenesis, highlighting the delicate harmony among unrelated cellular systems. Using the wbqL mutant, we also show that the normal assembly and growth properties of the crescentin structure are independent of its association with the cell envelope. However, this envelope association is important for facilitating the local disruption of the stable crescentin structure at the division site during cytokinesis

Construction of a high-resolution genetic linkage map and comparative genome analysis for the reef-building coral Acropora millepora

Section of Integrative Biology, School of Biological Sciences, University of Texas at Austin, 1 University Station C0930, Austin, TX 78712, USABackground: Worldwide, coral reefs are in decline due to a range of anthropogenic disturbances, and are now also under threat from global climate change. Virtually nothing is currently known about the genetic factors that might determine whether corals adapt to the changing climate or continue to decline. Quantitative genetics studies aiming to identify the adaptively important genomic loci will require a high-resolution genetic linkage map. The phylogenetic position of corals also suggests important applications for a coral genetic map in studies of ancestral metazoan genome architecture. Results: We constructed a high-resolution genetic linkage map for the reef-building coral Acropora millepora, the first genetic map reported for any coral, or any non-Bilaterian animal. More than 500 single nucleotide polymorphism (SNP) markers were developed, most of which are transferable in populations from Orpheus Island and Great Keppel Island. The map contains 429 markers (393 gene-based SNPs and 36 microsatellites) distributed in 14 linkage groups, and spans 1,493 cM with an average marker interval of 3.4 cM. Sex differences in recombination were observed in a few linkage groups, which may be caused by haploid selection. Comparison of the coral map with other metazoan genomes (human, nematode, fly, anemone and placozoan) revealed synteny regions. Conclusions: Our study develops a framework that will be essential for future studies of adaptation in coral and it also provides an important resource for future genome sequence assembly and for comparative genomics studies on the evolution of metazoan genome structure.Integrative [email protected]

SynFind: Compiling Syntenic Regions across Any Set of Genomes on Demand

The identification of conserved syntenic regions enables discovery of predicted locations for orthologous and homeologous genes, evenwhennosuchgeneispresent.Thiscapabilitymeansthatsynteny-basedmethodsarefarmoreeffectivethansequencesimilaritybased methods in identifying true-negatives, a necessity forstudying gene loss and gene transposition. However, the identification of syntenicregionsrequirescomplexanalyseswhichmustberepeatedforpairwisecomparisonsbetweenanytwospecies.Therefore,as the number of published genomes increases, there is a growing demand for scalable, simple-to-use applications to perform comparative genomic analyses that cater to both gene family studies and genome-scale studies. We implemented SynFind, a web-based tool that addresses this need. Given one query genome, SynFind is capable of identifying conserved syntenic regions in any set of targetgenomes.SynFindiscapableofreportingper-geneinformation,usefulforresearchersstudyingspecificgenefamilies,aswellas genome-wide data sets of syntenic gene and predicted gene locations, critical for researchers focused on large-scale genomic analyses. Inference of syntenic homologs provides the basis for correlation of functional changes around genes of interests between related organisms. Deployed on the CoGe online platform, SynFind is connected to the genomic data from over 15,000 organisms from all domains of life as well as supporting multiple releases of the same organism. SynFind makes use of a powerful job execution framework that promises scalability and reproducibility. SynFind can be accessed at http://genomevolution.org/CoGe/SynFind.pl. A video tutorial of SynFind using Phytophthrora as an example is available at http://www.youtube.com/watch?v=2Agczny9Nyc

Computational analysis of the <i>Caenorhabditis elegans</i> genome sequence.

The genomic sequencing of the model genetic organism, the nematode Caenorhabditis elegans is now essentially complete, representing the first genome sequence to be derived for a multicellular organism. This thesis describes the strategies and software tools that have been utilized in the analysis of the genomic sequence: Preliminary analysis of genomic organisation is also presented. C. elegans chromosomes do not store genetic information in a uniform manner. Gene density varies between different chromosomal regions and between chromosomes. The highly recombinagenic autosomal arms possess more repetitive elements and generally have a lower gene density than the recombinationally suppressed central regions. Although, the gene density within autosomal arms is higher than had been previously expected. A positive correlation is observed between the number of genetically defined loci from a chromosomal region and the expression rate of a region as estimated by the abundance of Expressed Sequence Tags (ESTs). A similar positive correlation is observed with the proportion of genes possessing similarity to rion-nematoda proteins. Chromosomal regions with a high density of gene clusters have fewer genetically derived loci. Demonstrating that redundancy reduces the genetic accessibility of a region towards classical genetic approaches. Introns are larger on the autosomal arms than the central clusters. Exon length shows no correlation with chromosomal position but increases with expression rate. Stop codon preference is also influenced by expression rate. Clusters of similar genes are also found on the C. elegans chromosomes although their distribution is not random. The majority of gene clusters have been determined to lie on chromosome V and the left arm of II. The orientation of the genes within gene clusters suggests that inversion events are common and provide a selective advantage. Alternative splicing has also been studied and the results suggest that many alternative transcripts can be attributed to errors in splice acceptor processing

Evidence and evolutionary analysis of ancient whole-genome duplication in barley predating the divergence from rice

<p>Abstract</p> <p>Background</p> <p>Well preserved genomic colinearity among agronomically important grass species such as rice, maize, Sorghum, wheat and barley provides access to whole-genome structure information even in species lacking a reference genome sequence. We investigated footprints of whole-genome duplication (WGD) in barley that shaped the cereal ancestor genome by analyzing shared synteny with rice using a ~2000 gene-based barley genetic map and the rice genome reference sequence.</p> <p>Results</p> <p>Based on a recent annotation of the rice genome, we reviewed the WGD in rice and identified 24 pairs of duplicated genomic segments involving 70% of the rice genome. Using 968 putative orthologous gene pairs, synteny covered 89% of the barley genetic map and 63% of the rice genome. We found strong evidence for seven shared segmental genome duplications, corresponding to more than 50% of the segmental genome duplications previously determined in rice. Analysis of synonymous substitution rates (Ks) suggested that shared duplications originated before the divergence of these two species. While major genome rearrangements affected the ancestral genome of both species, small paracentric inversions were found to be species specific.</p> <p>Conclusion</p> <p>We provide a thorough analysis of comparative genome evolution between barley and rice. A barley genetic map of approximately 2000 non-redundant EST sequences provided sufficient density to allow a detailed view of shared synteny with the rice genome. Using an indirect approach that included the localization of WGD-derived duplicated genome segments in the rice genome, we determined the current extent of shared WGD-derived genome duplications that occurred prior to species divergence.</p

Sgs1 and Exo1 Redundantly Inhibit Break-Induced Replication and De Novo Telomere Addition at Broken Chromosome Ends

In budding yeast, an HO endonuclease-inducible double-strand break (DSB) is efficiently repaired by several homologous recombination (HR) pathways. In contrast to gene conversion (GC), where both ends of the DSB can recombine with the same template, break-induced replication (BIR) occurs when only the centromere-proximal end of the DSB can locate homologous sequences. Whereas GC results in a small patch of new DNA synthesis, BIR leads to a nonreciprocal translocation. The requirements for completing BIR are significantly different from those of GC, but both processes require 5′ to 3′ resection of DSB ends to create single-stranded DNA that leads to formation of a Rad51 filament required to initiate HR. Resection proceeds by two pathways dependent on Exo1 or the BLM homolog, Sgs1. We report that Exo1 and Sgs1 each inhibit BIR but have little effect on GC, while overexpression of either protein severely inhibits BIR. In contrast, overexpression of Rad51 markedly increases the efficiency of BIR, again with little effect on GC. In sgs1Δ exo1Δ strains, where there is little 5′ to 3′ resection, the level of BIR is not different from either single mutant; surprisingly, there is a two-fold increase in cell viability after HO induction whereby 40% of all cells survive by formation of a new telomere within a few kb of the site of DNA cleavage. De novo telomere addition is rare in wild-type, sgs1Δ, or exo1Δ cells. In sgs1Δ exo1Δ, repair by GC is severely inhibited, but cell viaiblity remains high because of new telomere formation. These data suggest that the extensive 5′ to 3′ resection that occurs before the initiation of new DNA synthesis in BIR may prevent efficient maintenance of a Rad51 filament near the DSB end. The severe constraint on 5′ to 3′ resection, which also abrogates activation of the Mec1-dependent DNA damage checkpoint, permits an unprecedented level of new telomere addition