Browsing by Author "Moreno-Hagelsieb, Gabriel"

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    Conservation of adjacency as evidence of paralogous operons
    (2004-09) Janga, Sarath Chandra; Moreno-Hagelsieb, Gabriel
    Most of the analyses on the conservation of gene order are limited to orthologous genes. However, the organization of genes into operons might also result in the conservation of gene order of paralogous genes. Thus, we sought computational evidence that conservation of gene order of paralogous genes represents another level of conservation of genes in operons. We found that pairs of genes within experimentally characterized operons of Escherichia coli K12 and Bacillus subtilis tend to have more adjacently conserved paralogs than pairs of genes at transcription unit boundaries. The fraction of same strand gene pairs corresponding to conserved paralogs averages 0.07 with a maximum of 0.22 in Borrelia burgdorferi. The use of evidence from the conservation of adjacency of paralogous genes can improve the prediction of operons in E.coli K12 by ∼0.27 over predictions using conservation of adjacency of orthologous genes alone.
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    The distinctive signatures of promoter regions and operon junctions across prokaryotes
    (2006-08) Janga, Sarath Chandra; Lamboy, Warren F.; Huerta, Araceli M.; Moreno-Hagelsieb, Gabriel
    Here we show that regions upstream of first transcribed genes have oligonucleotide signatures that distinguish them from regions upstream of genes in the middle of operons. Databases of experimentally confirmed transcription units do not exist for most genomes. Thus, to expand the analyses into genomes with no experimentally confirmed data, we used genes conserved adjacent in evolutionarily distant genomes as representatives of genes inside operons. Likewise, we used divergently transcribed genes as representative examples of first transcribed genes. In model organisms, the trinucleotide signatures of regions upstream of these representative genes allow for operon predictions with accuracies close to those obtained with known operon data (0.8). Signature-based operon predictions have more similar phylogenetic profiles and higher proportions of genes in the same pathways than predicted transcription unit boundaries (TUBs). These results confirm that we are separating genes with related functions, as expected for operons, from genes not necessarily related, as expected for genes in different transcription units. We also test the quality of the predictions using microarray data in six genomes and show that the signature-predicted operons tend to have high correlations of expression. Oligonucleotide signatures should expand the number of tools available to identify operons even in poorly characterized genomes.
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    Global Functional Atlas of Escherichia coli Encompassing Previously Uncharacterized Proteins
    (2009-04) Hu, Pingzhao; Janga, Sarath Chandra; Babu, Mohan; Díaz-Mejía, J. Javier; Butland, Gareth; Yang, Wenhong; Pogoutse, Oxana; Guo, Xinghua; Phanse, Sadhna; Wong, Peter; Chandran, Shamanta; Christopoulos, Constantine; Nazarians-Armavil, Anaies; Nasseri, Negin Karimi; Musso, Gabriel; Ali, Mehrab; Nazemof, Nazila; Eroukova, Veronika; Golshani, Ashkan; Paccanaro, Alberto; Greenblatt, Jack F.; Moreno-Hagelsieb, Gabriel; Emili, Andrew
    One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the orphans' biological roles, we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions and 74,776 putative functional associations, most of which are novel. Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on network integration implicated the orphans in specific biological processes. We provide additional experimental evidence supporting orphan participation in protein synthesis, amino acid metabolism, biofilm formation, motility, and assembly of the bacterial cell envelope. This resource provides a “systems-wide” functional blueprint of a model microbe, with insights into the biological and evolutionary significance of previously uncharacterized proteins.
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    Nebulon: a system for the inference of functional relationships of gene products from the rearrangement of predicted operons
    (2005-04) Janga, Sarath Chandra; Collado-Vides, Julio; Moreno-Hagelsieb, Gabriel
    Since operons are unstable across Prokaryotes, it has been suggested that perhaps they re-combine in a conservative manner. Thus, genes belonging to a given operon in one genome might re-associate in other genomes revealing functional relationships among gene products. We developed a system to build networks of functional relationships of gene products based on their organization into operons in any available genome. The operon predictions are based on inter-genic distances. Our system can use different kinds of thresholds to accept a functional relationship, either related to the prediction of operons, or to the number of non-redundant genomes that support the associations. We also work by shells, meaning that we decide on the number of linking iterations to allow for the complementation of related gene sets. The method shows high reliability benchmarked against knowledge-bases of functional interactions. We also illustrate the use of Nebulon in finding new members of regulons, and of other functional groups of genes. Operon rearrangements produce thousands of high-quality new interactions per prokaryotic genome, and thousands of confirmations per genome to other predictions, making it another important tool for the inference of functional interactions from genomic context.
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    The partitioned Rhizobium etli genome: Genetic and metabolic redundancy in seven interacting replicons
    (2006-03) González, Víctor; Santamaria, Rosa I.; Bustos, Patricia; Hernández-González, Ismael; Medrano-Soto, Arturo; Moreno-Hagelsieb, Gabriel; Janga, Sarath Chandra; Ramírez, Miguel A.; Jiménez-Jacinto, Verónica; Collado-Vides, Julio; Dávila, Guillermo
    We report the complete 6,530,228-bp genome sequence of the symbiotic nitrogen fixing bacterium Rhizobium etli. Six large plasmids comprise one-third of the total genome size. The chromosome encodes most functions necessary for cell growth, whereas few essential genes or complete metabolic pathways are located in plasmids. Chromosomal synteny is disrupted by genes related to insertion sequences, phages, plasmids, and cell-surface components. Plasmids do not show synteny, and their orthologs are mostly shared by accessory replicons of species with multipartite genomes. Some nodulation genes are predicted to be functionally related with chromosomal loci encoding for the external envelope of the bacterium. Several pieces of evidence suggest an exogenous origin for the symbiotic plasmid (p42d) and p42a. Additional putative horizontal gene transfer events might have contributed to expand the adaptive repertoire of R. etli, because they include genes involved in small molecule metabolism, transport, and transcriptional regulation. Twenty-three putative sigma factors, numerous isozymes, and paralogous families attest to the metabolic redundancy and the genomic plasticity necessary to sustain the lifestyle of R. etli in symbiosis and in the soil.