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Rapid pair-wise synteny analysis of large bacterial genomes using web-based GeneOrder4.0
Padmanabhan Mahadevan, Donald Seto
BMC Research Notes , 2010, DOI: 10.1186/1756-0500-3-41
Abstract: GeneOrder4.0 is a web-based "on-the-fly" synteny and gene order analysis tool for comparative bacterial genomics (ca. 8 Mb). It enables the visualization of synteny by plotting protein similarity scores between two genomes and it also provides visual annotation of "hypothetical" proteins from older archived genomes based on more recent annotations.The web-based software tool GeneOrder4.0 is a user-friendly application that has been updated to allow the rapid analysis of synteny and gene order in large bacterial genomes. It is developed with the wet-bench researcher in mind.With the prospect now of very high-throughput and cost-effective DNA sequencing technology, and with its widespread applications routinely to many areas of biological interest, the number of available whole genome sequences grows at an astronomical rate. The Genomes Online Database (GOLD) [1] lists 957 complete and published bacterial genomes to date, with 3570 classified as "ongoing" (as of Dec. 2009). As a result of this tsunami of data, more genome analysis tools are needed in order to mine these data effectively, particularly for the bench scientist who may not be computer-savvy but is interested in using the genome data. Software tools have been developed for the analysis of gene order and synteny, which are important because they can be used to understand prokaryotic relationships and the evolution of their genomes [2], as well as to aid in gene function annotation [3], and to parse functional coupling prediction between genes in gene clusters [4]. In addition, new metrics are necessary in comparative genomics and systems biology to describe newly available sequenced genomes [5]; gene order and synteny may be used as one of these metrics to describe genomes.Unfortunately, some of these useful and needed software tools have become software "orphans" and are no longer available or supported, for one reason or another [6]. In addition, some tools are not easily available to a wet-bench investig
A Semi-Quantitative, Synteny-Based Method to Improve Functional Predictions for Hypothetical and Poorly Annotated Bacterial and Archaeal Genes  [PDF]
Alexis P. Yelton,Brian C. Thomas,Sheri L. Simmons,Paul Wilmes,Adam Zemla,Michael P. Thelen,Nicholas Justice,Jillian F. Banfield
PLOS Computational Biology , 2011, DOI: 10.1371/journal.pcbi.1002230
Abstract: During microbial evolution, genome rearrangement increases with increasing sequence divergence. If the relationship between synteny and sequence divergence can be modeled, gene clusters in genomes of distantly related organisms exhibiting anomalous synteny can be identified and used to infer functional conservation. We applied the phylogenetic pairwise comparison method to establish and model a strong correlation between synteny and sequence divergence in all 634 available Archaeal and Bacterial genomes from the NCBI database and four newly assembled genomes of uncultivated Archaea from an acid mine drainage (AMD) community. In parallel, we established and modeled the trend between synteny and functional relatedness in the 118 genomes available in the STRING database. By combining these models, we developed a gene functional annotation method that weights evolutionary distance to estimate the probability of functional associations of syntenous proteins between genome pairs. The method was applied to the hypothetical proteins and poorly annotated genes in newly assembled acid mine drainage Archaeal genomes to add or improve gene annotations. This is the first method to assign possible functions to poorly annotated genes through quantification of the probability of gene functional relationships based on synteny at a significant evolutionary distance, and has the potential for broad application.
Conservation of long-range synteny and microsynteny between the genomes of two distantly related nematodes
DB Guiliano, N Hall, SJM Jones, LN Clark, CH Corton, BG Barrell, ML Blaxter
Genome Biology , 2002, DOI: 10.1186/gb-2002-3-10-research0057
Abstract: An 83 kb region flanking the gene for Bm-mif-1 (macrophage migration inhibitory factor, a B. malayi homolog of a human cytokine) was sequenced. When compared to the complete genome of C. elegans, evidence for conservation of long-range synteny and microsynteny was found. Potential C. elegans orthologs for II of the 12 protein-coding genes predicted in the B. malayi sequence were identified. Ten of these orthologs were located on chromosome I, with eight clustered in a 2.3 Mb region. While several, relatively local, intrachromosomal rearrangements have occurred, the order, composition, and configuration of two gene clusters, each containing three genes, was conserved. Comparison of B. malayi BAC-end genome survey sequence to C. elegans also revealed a bias towards intrachromosome rearrangements.We suggest that intrachromosomal rearrangement is a major force driving chromosomal organization in nematodes, but is constrained by the interdigitation of functional elements of neighboring genes.All genomes encode conserved genes. The arrangement of these genes on chromosomal elements is determined by a balance between stochastic rearrangements and functional constraints. The level of conservation of gene order (synteny) and linkage between two genomes will depend on the relative contributions of inter- and intrachromosomal rearrangements. Whereas shared ancestry and functional constraints will increase conservation of linkage and synteny between taxa, rearrangement events will tend to randomize gene order over time. In the Metazoa, several gene clusters have been identified that remain linked because of functional constraints. These include the histone genes [1], the Hox gene clusters [2], the immunoglobulin cluster [3], and the major histocompatibility complex (MHC) [4], but most genes are believed to be free to move within the genome. The tempo of gene rearrangement varies between taxa [5,6]. Vertebrate chromosomes are mosaic structures containing large conserved segments
Large synteny blocks revealed between Caenorhabditis elegans and Caenorhabditis briggsae genomes using OrthoCluster
Ismael A Vergara, Nansheng Chen
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-516
Abstract: Initial identification and analysis of synteny blocks using OrthoCluster enabled us to systematically improve the genome annotation of C. elegans and C. briggsae, identifying 52 potential novel genes in C. elegans, 582 in C. briggsae, and 949 novel orthologous relationships between these two species. Using the improved annotation, we have detected 3,058 perfect synteny blocks that contain no mismatches between C. elegans and C. briggsae. Among these synteny blocks, the majority are mapped to homologous chromosomes, as previously reported. The largest perfect synteny block contains 42 genes, which spans 201.2 kb in Chromosome V of C. elegans. On average, perfect synteny blocks span 18.8 kb in length. When some mismatches (interruptions) are allowed, synteny blocks ("imperfect synteny blocks") that are much larger in size are identified. We have shown that the majority (80%) of the C. elegans and C. briggsae genomes are covered by imperfect synteny blocks. The largest imperfect synteny block spans 6.14 Mb in Chromosome X of C. elegans and there are 11 synteny blocks that are larger than 1 Mb in size. On average, imperfect synteny blocks span 63.6 kb in length, larger than previously reported.We have demonstrated that OrthoCluster can be used to accurately identify synteny blocks and have found that synteny blocks between C. elegans and C. briggsae are almost three-folds larger than previously identified.The conservation of large scale genomic sequences across two or more genomes --synteny blocks-- is of primary interest because their identification sets up a stage for identifying and characterizing sequence and functional differences among genomes [1]. The term synteny has been used in different contexts in the past. Originally, synteny was used to indicate the colocalization of different genes in corresponding chromosomes of different species (a.k.a. "chromosomal synteny") [2]. Recently, with the availability of thousands of sequenced genomes, synteny has been used t
Synteny conservation between the Prunus genome and both the present and ancestral Arabidopsis genomes
Sook Jung, Dorrie Main, Margaret Staton, Ilhyung Cho, Tatyana Zhebentyayeva, Pere Arús, Albert Abbott
BMC Genomics , 2006, DOI: 10.1186/1471-2164-7-81
Abstract: We analyzed the synteny conservation between the Prunus and the Arabidopsis genomes by comparing 475 peach ESTs that are anchored to Prunus genetic maps and their Arabidopsis homologs detected by sequence similarity. Microsyntenic regions were detected between all five Arabidopsis chromosomes and seven of the eight linkage groups of the Prunus reference map. An additional 1097 peach ESTs that are anchored to 431 BAC contigs of the peach physical map and their Arabidopsis homologs were also analyzed. Microsyntenic regions were detected in 77 BAC contigs. The syntenic regions from both data sets were short and contained only a couple of conserved gene pairs. The synteny between peach and Arabidopsis was fragmentary; all the Prunus linkage groups containing syntenic regions matched to more than two different Arabidopsis chromosomes, and most BAC contigs with multiple conserved syntenic regions corresponded to multiple Arabidopsis chromosomes. Using the same peach EST datasets and their Arabidopsis homologs, we also detected conserved syntenic regions in the pseudo-ancestral Arabidopsis genome. In many cases, the gene order and content of peach regions was more conserved in the ancestral genome than in the present Arabidopsis region. Statistical significance of each syntenic group was calculated using simulated Arabidopsis genome.We report here the result of the first extensive analysis of the conserved microsynteny using DNA sequences across the Prunus genome and their Arabidopsis homologs. Our study also illustrates that both the ancestral and present Arabidopsis genomes can provide a useful resource for marker saturation and candidate gene search, as well as elucidating evolutionary relationships between species.The eukaryote genome size is vastly diverse and is not dependent on the genetic and organismal complexity. Most of the DNA in large genomes, however, is non-coding and the gene content is relatively constant [1,2]. Arabidopsis thaliana (estimated haploid size
Sibelia: A scalable and comprehensive synteny block generation tool for closely related microbial genomes  [PDF]
Ilya Minkin,Anand Patel,Mikhail Kolmogorov,Nikolay Vyahhi,Son Pham
Quantitative Biology , 2013,
Abstract: Comparing strains within the same microbial species has proven effective in the identification of genes and genomic regions responsible for virulence, as well as in the diagnosis and treatment of infectious diseases. In this paper, we present Sibelia, a tool for finding synteny blocks in multiple closely related microbial genomes using iterative de Bruijn graphs. Unlike most other tools, Sibelia can find synteny blocks that are repeated within genomes as well as blocks shared by multiple genomes. It represents synteny blocks in a hierarchy structure with multiple layers, each of which representing a different granularity level. Sibelia has been designed to work efficiently with a large number of microbial genomes; it finds synteny blocks in 31 S. aureus genomes within 31 minutes and in 59 E.coli genomes within 107 minutes on a standard desktop. Sibelia software is distributed under the GNU GPL v2 license and is available at: https://github.com/bioinf/Sibelia Sibelia's web-server is available at: http://etool.me/software/sibelia
A Genome-Wide Survey of Switchgrass Genome Structure and Organization  [PDF]
Manoj K. Sharma, Rita Sharma, Peijian Cao, Jerry Jenkins, Laura E. Bartley, Morgan Qualls, Jane Grimwood, Jeremy Schmutz, Daniel Rokhsar, Pamela C. Ronald
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033892
Abstract: The perennial grass, switchgrass (Panicum virgatum L.), is a promising bioenergy crop and the target of whole genome sequencing. We constructed two bacterial artificial chromosome (BAC) libraries from the AP13 clone of switchgrass to gain insight into the genome structure and organization, initiate functional and comparative genomic studies, and assist with genome assembly. Together representing 16 haploid genome equivalents of switchgrass, each library comprises 101,376 clones with average insert sizes of 144 (HindIII-generated) and 110 kb (BstYI-generated). A total of 330,297 high quality BAC-end sequences (BES) were generated, accounting for 263.2 Mbp (16.4%) of the switchgrass genome. Analysis of the BES identified 279,099 known repetitive elements, >50,000 SSRs, and 2,528 novel repeat elements, named switchgrass repetitive elements (SREs). Comparative mapping of 47 full-length BAC sequences and 330K BES revealed high levels of synteny with the grass genomes sorghum, rice, maize, and Brachypodium. Our data indicate that the sorghum genome has retained larger microsyntenous regions with switchgrass besides high gene order conservation with rice. The resources generated in this effort will be useful for a broad range of applications.
Positional Homology in Bacterial Genomes
Ingrid J. Burgetz,Salimah Shariff,Andy Pang,Elisabeth R. M. Tillier
Evolutionary Bioinformatics , 2006,
Abstract: In comparative genomic studies, syntenic groups of homologous sequence in the same order have been used as supplementary information that can be used in helping to determine the orthology of the compared sequences. The assumption is that orthologous gene copies are more likely to share the same genome positions and share the same gene neighbors. In this study we have defined positional homologs as those that also have homologous neighboring genes and we investigated the usefulness of this distinction for bacterial comparative genomics. We considered the identification of positionaly homologous gene pairs in bacterial genomes using protein and DNA sequence level alignments and found that the positional homologs had on average relatively lower rates of substitution at the DNA level (synonymous substitutions) than duplicate homologs in different genomic locations, regardless of the level of protein sequence divergence (measured with non-synonymous substitution rate). Since gene order conservation can indicate accuracy of orthology assignments, we also considered the effect of imposing certain alignment quality requirements on the sensitivity and specificity of identification of protein pairs by BLAST and FASTA when neighboring information is not available and in comparisons where gene order is not conserved. We found that the addition of a stringency filter based on the second best hits was an efficient way to remove dubious ortholog identifications in BLAST and FASTA analyses. Gene order conservation and DNA sequence homology are useful to consider in comparative genomic studies as they may indicate different orthology assignments than protein sequence homology alone.
Comparative insect mitochondrial genomes: Differences despite conserved genome synteny
SBC Chandra, JL Vlk, V Kapatral
African Journal of Biotechnology , 2006,
Abstract: We present a comparative analysis of select insect mitochondrial DNA (mtDNA) representing four insect orders (Diptera, Hymenoptera, Orthoptera and Coleoptera) consisting of 12 different species in an effort to study a common set of genes and to understand the evolution of mitochondrial genome. A functional analysis of mitochondrial genomes was carried out using ERGO bioinformatics suite. To compare the similarity between closely related insect mitochondrial genome sequences, dot-plot comparisons of sequences were performed. LSU and SSU rRNA sequences were used to construct a phylogenetic tree to determine the relationship among four insect orders. LSU rRNA sequences yielded a tree with branching patterns reflecting the expected pattern as insect species belonging to different orders were put into separate clades. Based on the sequence similarity, insect species belonging to four different orders in general appear to be closely related. However, a comparative and functional analysis of insect mitochondria sequences revealed differences in gene organization of mtDNA. Although tRNA species were identical in most species of insects, their position and the transcription orientations were different, reflecting differential transcriptions. Based on this study we conclude that, although the gene types are very similar across these insect orders, significant differences in GC content perhaps suggest multiple mitochondrial ancestors
GeneOrder3.0: Software for comparing the order of genes in pairs of small bacterial genomes
Srikanth Celamkoti, Sashidhara Kundeti, Anjan Purkayastha, Raja Mazumder, Charles Buck, Donald Seto
BMC Bioinformatics , 2004, DOI: 10.1186/1471-2105-5-52
Abstract: GeneOrder3.0 has been developed and validated successfully on several small bacterial genomes (ca. 580 kb to 1.83 Mb) archived in the NCBI GenBank database. It is an updated web-based "on-the-fly" computational tool allowing gene order and synteny comparisons of any two small bacterial genomes. Analyses of several bacterial genomes show that a large amount of gene and genome re-arrangement occurs, as seen with earlier DNA software tools. This can be displayed at the protein level using GeneOrder3.0. Whole genome alignments of genes are presented in both a table and a dot plot. This allows the detection of evolutionary more distant relationships since protein sequences are more conserved than DNA sequences.GeneOrder3.0 allows researchers to perform comparative analysis of gene order and synteny in genomes of sizes up to 2 Mb "on-the-fly." Availability: http://binf.gmu.edu/genometools.html webcite and http://pasteur.atcc.org:8050/GeneOrder3.0 webcite.Whole genome DNA sequence data are being generated and deposited into proprietary and public domain databases at an increasingly rapid rate as a result of more efficient and less expensive DNA sequencing and analysis technology. An on-line database, http://www.genomesonline.org webcite[1], lists a running count of 182 published complete genomes with 488 on-going prokaryotic genome projects as of March 26, 2004.There are relatively few whole genome comparison software tools owing to the previous paucity of whole genome data. However, there are a growing number of these tools available, and along with earlier versions of GeneOrder and CoreGenes [2-4], there is increasing interest in developing software comparing the gene order and synteny of whole genomes at the gene level, as evidenced by two recent publications [5,6].As genome sequencing projects are completed, greater scientific curiosity and attention focuses on the analysis and data mining of these whole genomes. In turn, this stimulates additional interest in obtainin
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