PubMed Health⌕ Search

Biomedical subjects

Julio Collado-Vides

Publications and source records attributed to Julio Collado-Vides.

36 records · Page 2Linked to original sources
PubMed2004

Successful lateral transfer requires codon usage compatibility between foreign genes and recipient genomes.

We present evidence supporting the notion that codon usage (CU) compatibility between foreign genes and recipient genomes is an important prerequisite to assess the selective advantage of imported functions, and therefore to increase the fixation probability of horizontal gene transfer (HGT) events. This contrasts with the current tendency in research to predict recent HGTs in prokaryotes by assuming that acquired genes generally display poor CU. By looking at the CU level (poor, typical, or rich) exhibited by putative xenologs still resembling their original CU, we found that most alien genes predominantly present typical CU immediately upon introgression, thereby suggesting that the role of CU amelioration in HGT has been overemphasized. In our strategy, we first scanned a representative set of 103 complete prokaryotic genomes for all pairs of candidate xenologs (exported/imported genes) displaying similar CU. We applied additional filtering criteria, including phylogenetic validations, to enhance the reliability of our predictions. Our approach makes no assumptions about the CU of foreign genes being typical or atypical within the recipient genome, thus providing a novel unbiased framework to study the evolutionary dynamics of HGT.

Archaea↗
PubMed2004

Distribution of minigenes in the bacteriophage lambda chromosome.

The bar loci in the chromosome of bacteriophage lambda inhibit phage vegetative growth in bacteria defective for peptidyl-tRNA hydrolase (Pth). Expression of the bar regions results in accumulation of peptidyl-tRNA, inhibition of protein synthesis, and arrest of mutant cell growth. These effects have been ascribed to the expression of two-codon ORFs present in translatable sequences named 'minigenes' in the lambda bar regions. To investigate the nature, frequency, and distribution of minigenes in the phage genome, we conducted a survey of their location in lambda DNA. A short-fragment random genomic DNA library was constructed for the identification of clones inhibitory of Pth-defective cells (bar-like phenotype). Three new bar-like minigenes were identified in the library but only one was on the sense strand and it had a rare initiation codon. This result contrasted with the in silico identification of over a hundred putative minigenes using an ad hoc computer program on both strands of lambda DNA. Unlike bar constructs, most of the toxic constructed clones were also toxic to wild-type bacteria, thus suggesting a different inhibition mechanism. Sequence analysis of these cloned inserts showed that they harbored minigenes, mini-ORFs, gene starts, gene ends, or combinations thereof. Our data suggest that minigene-like sequences may, at least partly, account for toxicity in wild-type cells. We propose that clustering of minigenes at gene ends may play a role in gene expression. Other minigenes identified in silico were non-toxic. It is still an open question what the in vivo function of these and toxic minigenes might be.

Bacteriophage lambda↗
PubMed2004

RegulonDB (version 4.0): transcriptional regulation, operon organization and growth conditions in Escherichia coli K-12.

RegulonDB is the primary database of the major international maintained curation of original literature with experimental knowledge about the elements and interactions of the network of transcriptional regulation in Escherichia coli K-12. This includes mechanistic information about operon organization and their decomposition into transcription units (TUs), promoters and their sigma type, binding sites of specific transcriptional regulators (TRs), their organization into 'regulatory phrases', active and inactive conformations of TRs, as well as terminators and ribosome binding sites. The database is complemented with clearly marked computational predictions of TUs, promoters and binding sites of TRs. The current version has been expanded to include information beyond specific mechanisms aimed at gathering different growth conditions and the associated induced and/or repressed genes. RegulonDB is now linked with Swiss-Prot, with microarray databases, and with a suite of programs to analyze and visualize microarray experiments. We provide a summary of the biological knowledge contained in RegulonDB and describe the major changes in the design of the database. RegulonDB can be accessed on the web at the URL: http://www.cifn.unam.mx/Computational_Biology/regulondb/.

Databases, Factual↗
PubMed2004

Phylogenetic distribution of DNA-binding transcription factors in bacteria and archaea.

We have addressed the distribution and abundance of 75 transcription factor (TF) families in complete genomes from 90 different bacterial and archaeal species. We found that the proportion of TFs increases with genome size. The deficit of TFs in some genomes might be compensated by the presence of proteins organizing and compacting DNA, such as histone-like proteins. Nine families are represented in all the bacteria and archaea we analyzed, whereas 17 families are specific to bacteria, providing evidence for regulon specialization at an early stage of evolution between the bacterial and archeal lineages. Ten of the 17 families identified in bacteria belong exclusively to the proteobacteria defining a specific signature for this taxonomical group. In bacteria, 10 families are lost mostly in intracellular pathogens and endosymbionts, while 9 families seem to have been horizontally transferred to archaea. The winged helix-turn-helix (HTH) is by far the most abundant structure (motif) in prokaryotes, and might have been the earliest HTH motif to appear as shown by its distribution and abundance in both bacterial and archaeal cellular domains. Horizontal gene transfer and lineage-specific gene losses suggest a progressive elimination of TFs in the course of archaeal and bacterial evolution. This analysis provides a framework for discussing the selective forces directing the evolution of the transcriptional machinery in prokaryotes.

Amino Acid Sequence↗
PubMed2003

Environmental conditions and transcriptional regulation in Escherichia coli: a physiological integrative approach.

Bacteria develop a number of devices for sensing, responding, and adapting to different environmental conditions. Understanding within a genomic perspective how the transcriptional machinery of bacteria is modulated, as a response for changing conditions, is a major challenge for biologists. Knowledge of which genes are turned on or turned off under specific conditions is essential for our understanding of cell behavior. In this study we describe how the information pertaining to gene expression and associated growth conditions (even with very little knowledge of the associated regulatory mechanisms) is gathered from the literature and incorporated into RegulonDB, a database on transcriptional regulation and operon organization in E. coli. The link between growth conditions, signal transduction, and transcriptional regulation is modeled in the database in a simple format that highlights biological relevant information. As far as we know, there is no other database that explicitly clarifies the effect of environmental conditions on gene transcription. We discuss how this knowledge constitutes a benchmark that will impact future research aimed at integration of regulatory responses in the cell; for instance, analysis of microarrays, predicting culture behavior in biotechnological processes, and comprehension of dynamics of regulatory networks. This integrated knowledge will contribute to the future goal of modeling the behavior of E. coli as an entire cell. The RegulonDB database can be accessed on the web at the URL: http://www.cifn.unam.mx/Computational_Biology/regulondb/.

Adaptation, Physiological↗
PubMed2003

Conservation of DNA curvature signals in regulatory regions of prokaryotic genes.

DNA curvature plays a well-characterized role in many transcriptional regulation mechanisms. We present evidence for the conservation of curvature signals in putative regulatory regions of several archaeal and eubacterial genomes. Genes with highly curved upstream regions were identified in orthologous groups, based on the annotations of the Cluster of Orthologous Groups of proteins (COG) database. COGs possessing a significant number of genes with curvature signals were analyzed, and conserved properties were found in several cases. Curvature signals related to regulatory sites, previously described in single organisms, were located in a broad spectrum of bacterial genomes. Global regulatory proteins, such as HU, IHF and FIS, known to bind to curved DNA and to be autoregulated, were found to present conserved DNA curvature signals in their regulatory regions, emphasizing the fact that structural parameters of the DNA molecule are conserved elements in the process of transcriptional regulation of some systems. It is currently an open question whether these diverse systems are part of an integrated global regulatory response in different microorganisms.

Cell Division↗
PubMed2003

Sigma70 promoters in Escherichia coli: specific transcription in dense regions of overlapping promoter-like signals.

We present here a computational analysis showing that sigma70 house-keeping promoters are located within zones with high densities of promoter-like signals in Escherichia coli, and we introduce strategies that allow for the correct computer prediction of sigma70 promoters. Based on 599 experimentally verified promoters of E.coli K-12, we generated and evaluated more than 200 weight matrices optimizing different criteria to obtain the best recognition matrices. The alignments generating the best statistical models did not fully correspond with the canonical sigma70 model. However, matrices that correspond to such a canonical model performed better as tools for prediction. We tested the predictive capacity of these matrices on 250 bp long regions upstream of gene starts, where 90% of the known promoters occur. The computational matrix models generated an average of 38 promoter-like signals within each 250 bp region. In more than 50% of the cases, the true promoter does not have the best score within the region. We observed, in fact, that real promoters occur mostly within regions with high densities of overlapping putative promoters. We evaluated several strategies to identify promoters. The best one uses an intrinsic score of the -10 and -35 hexamers that form the promoter as well as an extrinsic score that uses the distribution of promoters from the start of the gene. We were able to identify 86% true promoters correctly, generating an average of 4.7 putative promoters per region as output, of which 3.7, on average, exist in clusters, as a series of overlapping potentially competing RNA polymerase-binding sites. As far as we know, this is the highest predictive capability reported so far. This high signal density is found mainly within regions upstream of genes, contrasting with coding regions and regions located between convergently transcribed genes. These results are consistent with experimental evidence that show the existence of multiple overlapping promoter sites that become functional under particular conditions. This density is probably the consequence of a rich number of vestiges of promoters in evolution. We suggest that transcriptional regulators as well as other functional promoters play an important role in keeping these latent signals suppressed.

Bacterial Proteins↗
PubMed2003

The mosaic structure of the symbiotic plasmid of Rhizobium etli CFN42 and its relation to other symbiotic genome compartments.

BACKGROUND: Symbiotic bacteria known as rhizobia interact with the roots of legumes and induce the formation of nitrogen-fixing nodules. In rhizobia, essential genes for symbiosis are compartmentalized either in symbiotic plasmids or in chromosomal symbiotic islands. To understand the structure and evolution of the symbiotic genome compartments (SGCs), it is necessary to analyze their common genetic content and organization as well as to study their differences. To date, five SGCs belonging to distinct species of rhizobia have been entirely sequenced. We report the complete sequence of the symbiotic plasmid of Rhizobium etli CFN42, a microsymbiont of beans, and a comparison with other SGC sequences available. RESULTS: The symbiotic plasmid is a circular molecule of 371,255 base-pairs containing 359 coding sequences. Nodulation and nitrogen-fixation genes common to other rhizobia are clustered in a region of 125 kilobases. Numerous sequences related to mobile elements are scattered throughout. In some cases the mobile elements flank blocks of functionally related sequences, thereby suggesting a role in transposition. The plasmid contains 12 reiterated DNA families that are likely to participate in genomic rearrangements. Comparisons between this plasmid and complete rhizobial genomes and symbiotic compartments already sequenced show a general lack of synteny and colinearity, with the exception of some transcriptional units. There are only 20 symbiotic genes that are shared by all SGCs. CONCLUSIONS: Our data support the notion that the symbiotic compartments of rhizobia genomes are mosaic structures that have been frequently tailored by recombination, horizontal transfer and transposition.

Anaerobiosis↗
PubMed2003

Identifying global regulators in transcriptional regulatory networks in bacteria.

The machinery for cells to take decisions, when environmental conditions change, includes protein-DNA interactions defined by transcriptional factors and their targets around promoters. Properties of global regulators are revised attempting to reach diagnostic explicit criteria for their definition and eventual future computational identification. These include among others, the number of regulated genes, the number and type of co-regulators, the different sigma-classes of promoters and the number of transcriptional factors they regulate, the size of the evolutionary family they belong to, and the variety of conditions where they exert their control. As a consequence, global versus local regulation can be identified, as shown for Escherichia coli and eventually in other genomes.

Bacteria↗
PubMed2003

Regulatory network of Escherichia coli: consistency between literature knowledge and microarray profiles.

The transcriptional network of Escherichia coli may well be the most complete experimentally characterized network of a single cell. A rule-based approach was built to assess the degree of consistency between whole-genome microarray experiments in different experimental conditions and the accumulated knowledge in the literature compiled in RegulonDB, a data base of transcriptional regulation and operon organization in E. coli. We observed a high and statistical significant level of consistency, ranging from 70%-87%. When effector metabolites of regulatory proteins are not considered in the prediction of the active or inactive state of the regulators, consistency falls by up to 40%. Similarly, consistency decreases when rules for multiple regulatory interactions are altered or when "on" and "off" entries were assigned randomly. We modified the initial state of regulators and evaluated the propagation of errors in the network that do not correlate linearly with the connectivity of regulators. We interpret this deviation mainly as a result of the existence of redundant regulatory interactions. Consistency evaluation opens a new space of dialogue between theory and experiment, as the consequences of different assumptions can be evaluated and compared.

Databases, Genetic↗
PubMed2003

Regulation of expression of symbiotic genes in Rhizobium sp. NGR234.

Research in the field of Rhizobium-legume symbiosis faces a new challenge: integrate the wealth of information generated by genomic projects. The goal: apprehend the complexity of the molecular mechanisms involved in symbiotic associations. At the time of writing, the genomes of three micro-symbionts (Bradyrhizobium japonicum, Mesorhizobium loti and Sinorhizobium meliloti) have been sequenced, and two more (those of Rhizobium leguminosarum and Rhizobium etli) will be completed in the near future. Together, completed rhizobial genomes represent already 23,393,822 bp of DNA sequence and 21,797 predicted open reading frames (ORFs). To identify candidate-symbiotic genes in such a broad database, predict their function and dissect the regulatory networks that govern their expression are no simple tasks. One way to confront this problem is to combine different datasets, in particular genetic and transcriptional maps as well as predicted promoters from bioinformatics analyses. Here, we would like to illustrate this type of approach with the analysis of the symbiotic plasmid (pNGR234a) of the broad host-range Rhizobium sp. NGR234.

Gene Expression Regulation, Bacterial↗
PubMed2002

Evaluation of thresholds for the detection of binding sites for regulatory proteins in Escherichia coli K12 DNA.

BACKGROUND: Sites in DNA that bind regulatory proteins can be detected computationally in various ways. Pattern discovery methods analyze collections of genes suspected to be co-regulated on the evidence, for example, of clustering of transcriptome data. Pattern searching methods use sequences with known binding sites to find other genes regulated by a given protein. Such computational methods are important strategies in the discovery and elaboration of regulatory networks and can provide the experimental biologist with a precise prediction of a binding site or identify a gene as a member of a set of co-regulated genes (a regulon). As more variations on such methods are published, however, thorough evaluation is necessary, as performance may differ depending on the conditions of use. Detailed evaluation also helps to improve and understand the behavior of the different methods and computational strategies. RESULTS: We used a collection of 86 regulons from Escherichia coli as datasets to evaluate two methods for pattern discovery and pattern searching: dyad analysis/dyad sweeping using the program Dyad-analysis, and multiple alignment using the programs Consensus/Patser. Clearly defined statistical parameters are used to evaluate the two methods in different situations. We placed particular emphasis on minimizing the rate of false positives. CONCLUSIONS: As a general rule, sensors obtained from experimentally reported binding sites in DNA frequently locate true sites as the highest-scoring sequences within a given upstream region, especially using Consensus/Patser. Pattern discovery is still an unsolved problem, although in the cases where Dyad-analysis finds significant dyads (around 50%), these frequently correspond to true binding sites. With more robust methods, regulatory predictions could help identify the function of unknown genes.

Bacterial Proteins↗
PubMed2002

The EcoCyc Database.

EcoCyc is an organism-specific pathway/genome database that describes the metabolic and signal-transduction pathways of Escherichia coli, its enzymes, its transport proteins and its mechanisms of transcriptional control of gene expression. EcoCyc is queried using the Pathway Tools graphical user interface, which provides a wide variety of query operations and visualization tools. EcoCyc is available at http://ecocyc.org/.

Database Management Systems↗
PubMed2002

Analysis of the cellular functions of Escherichia coli operons and their conservation in Bacillus subtilis.

The common assumption of operons as composed of genes that cooperate in a biological process is confirmed here by showing that Escherichia coli operons tend to be composed of genes that belong to the same general class of cellular function. Furthermore, the comparison between the genomic organization of E. coli and that of Bacillus subtilis shows that the genes that are homologous to genes that belong to experimentally characterized E. coli operons tend to cluster in neighboring regions of the genome. This tendency is greater for the subset of E. coli operons whose genes belong to a single functional class. These observations indicate strong evolutionary pressure that, translated into functional constraints, leads to the inclusion of many essential functions in conserved operons and clusters in these two distant species.

Bacillus subtilis↗
PubMed2002

A powerful non-homology method for the prediction of operons in prokaryotes.

MOTIVATION: The prediction of the transcription unit organization of genomes is an important clue in the inference of functional relationships of genes, the interpretation and evaluation of transcriptome experiments, and the overall inference of the regulatory networks governing the expression of genes in response to the environment. Though several methods have been devised to predict operons, most need a high characterization of the genome analysed. Log-likelihoods derived from inter-genic distance distributions work surprisingly well to predict operons in Escherichia coli and are available for any genome as soon as the gene sets are predicted. RESULTS: Here we provide evidence that the very same method is applicable to any prokaryotic genome. First, the method has the same efficiency when evaluated using a collection of experimentally known operons of Bacillus subtilis. Second, operons among most if not all prokaryotes seem to have the same tendencies to keep short distances between their genes, the most frequent distances being the overlaps of four and one base pairs. The universality of this structural feature allows us to predict the organization of transcription units in all prokaryotes. Third, predicted operons contain a higher proportion of genes with related phylogenetic profiles and conservation of adjacency than predicted borders of transcription units.

Algorithms↗
PubMed2002

Operon conservation from the point of view of Escherichia coli, and inference of functional interdependence of gene products from genome context.

We have previously demonstrated that genes within experimentally characterized operons of Escherichia coli are conserved together in other genomes more frequently than genes at the borders of transcription units. Here we expand the analyses and show that, as the phylogenetic distance of the genomes compared increases, the genes remaining together must belong to genes associated into operons in other prokaryotes regardless of the operon organization of the corresponding orthologous gene pair of E. coli. At the same time, we show that the observed tendencies of genes within operons to keep very short inter-genic distances in E. coli, is the same in any other prokaryote whose genome is currently available. We also show the relationship between our analyses of conservation and the inference of functional relationships from genomic context.

Computational Biology↗
PubMed2002

Towards a bioinformatics network for Latin America and the Caribbean (LACBioNet).

Bioinformatics is increasingly recognised as a crucial field for research and development in the biological sciences, and forms an integral part of genomics, proteomics and modern biotechnology. Worldwide participation is important, and scientists in developing countries can contribute to this field. Regional networks for bioinformatics are highly beneficial for capacity strengthening and cooperation, and for establishing productive interactions between scientists in the fields of biological and informatics sciences. Such a network (LACBioNet) is being organised for Latin America and the Caribbean. Its immediate goals include the organisation and extension of nodes and services, information and communication, research and development in different specialty fields of bioinformatics, and training and human resource development.

Caribbean Region↗