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Biomedical subjects

Howard Ochman

Publications and source records attributed to Howard Ochman.

31 records · Page 2Linked to original sources
PubMed2003

Neutral mutations and neutral substitutions in bacterial genomes.

Molecular evolutionary biologists usually assess the underlying spectrum of mutations within a bacterial genome by examining substitutions that occur at sites believed to be under no selective constraints. Alternatively, bacterial mutation rates can also be estimated in a variety of experimental systems. The two classes of changes occurring in DNA sequences-i.e., mutations and neutral substitutions-are, in theory, identical; however, the rates and patterns of mutations in bacteria, as inferred from sequence comparisons, often differ significantly from those derived experimentally. These differences have resulted in conflicting interpretations of the nonselective forces that affect mutation rates.

Amino Acid Substitution↗
PubMed2003

Quartet mapping and the extent of lateral transfer in bacterial genomes.

Several recent analyses have used quartet-based methods to assess the congruence among phylogenies derived for large sets of genes from prokaryotic genomes. The principal conclusion from these studies is that lateral gene transfer (LGT) has blurred prokaryotic phylogenies to such a degree that the darwinian scheme of treelike evolution might be abandoned in favor of a net or web. Here, we focus on one of these methods, quartet mapping, and show that its application can lead to overestimation of the extent of inferred LGT in prokaryotes, particularly when applied to distantly related taxa.

Bacteria↗
PubMed2003

Phylogenetics and the cohesion of bacterial genomes.

Gene acquisition is an ongoing process in many bacterial genomes, contributing to adaptation and ecological diversification. Lateral gene transfer is considered the primary explanation for discordance among gene phylogenies and as an obstacle to reconstructing the tree of life. We measured the extent of phylogenetic conflict and alien-gene acquisition within quartets of sequenced genomes. Although comparisons of complete gene inventories indicate appreciable gain and loss of genes, orthologs available for phylogenetic reconstruction are consistent with a single tree.

Bacteria↗
PubMed2003

Transcription increases multiple spontaneous point mutations in Salmonella enterica.

The spontaneous rate of G.C-->A.T mutations and a hotspot T.A-->G.C transversion are known to increase with the frequency of transcription-increases that have been ascribed primarily to processes that affect only these specific mutations. To investigate how transcription induces other spontaneous point mutations, we tested for its effects in repair-proficient Salmonella enterica using reversion assays of chromosomally inserted alleles. Our results indicate that transcription increases rates of all tested point mutations in the induced gene: induction significantly increased the individual rates of an A.T-->T.A transversion, an A.T-->G.C transition and the pooled rates of the three other point mutations assayed. Although the S.enterica genome is thought to have a mutational bias towards G.C base pairs, transitions creating A.T pairs were approximately 10 times more frequent than the reverse mutation, resulting in an overall mutation pressure to lower G+C contents. Transitions occurred at roughly twice the rate of transversions, similar to results from sequence comparisons; however, several individual transversions are more frequent than the least common transition.

Drug Resistance, Bacterial↗
PubMed2003

Loss of DNA recombinational repair enzymes in the initial stages of genome degeneration.

Many obligate intracellular pathogens and symbionts undergo genome degeneration during long-term association with eukaryotic hosts; however, very little is known about genome changes that occur in the initial stages of such intracellular associations. By focusing on a clade of bacteria that have recently established symbiotic associations with insect hosts, we have identified events that may contribute to the reduction and degeneration of symbiont genomes. Unlike virtually all other bacteria, the obligate symbionts of maize and rice weevils each display substantial sequence divergence between multiple copies of their rDNA genes, resulting from a reduction in the efficacy of recombinational gene conversion, coincident with the inactivation of the recombinational repair gene recF in the common ancestor of both symbionts. The maize weevil endosymbiont also lacks a functional recA, resulting in further reduction in the efficacy of gene conversion between paralogous rDNAs and in a novel IS-mediated deletion in a 23S rDNA gene. Similar events may be pervasive during the evolution of symbiosis because symbiont genomes typically lack recombinational repair genes and have reduced numbers of ribosomal operons.

Animals↗
PubMed2003

Eyeing bacterial genomes.

The density of information in a bacterial genome allows its history, organization and encoded functions to be distilled into a single graphical representation. These features have made it possible to discern the forces acting in and on bacterial genomes at levels not attainable in eukaryotes.

Bacteria↗
PubMed2003

Intracellular symbionts of sharpshooters (Insecta: Hemiptera: Cicadellinae) form a distinct clade with a small genome.

The leafhoppers (Insecta: Hemiptera: Cicadellidae) are the most species-rich group of invertebrates in which intracellular symbionts are usual. Here we present the first molecular characterization of bacteriome-associates in the leafhoppers, with focus on the subfamily Cicadellinae (sharpshooters). Phylogenetic analyses of 16S rDNA sequences from intracellular symbionts residing in the bacteriomes of five host species indicate that these symbionts form a well-defined clade within the gamma-3 Proteobacteria, consistent with an ancient colonization and strict vertical transmission. More extensive gene sequence information is reported for the symbiont of Homalodisca coagulata (Say). The genome size, as determined by pulsed field gel electrophoresis, is approximately 680 kb. This finding, when combined with published results for symbionts of aphids, ants, psyllids and tsetse flies, adds to an emerging pattern which suggests that bacteriome associates often descend from ancient infections by gamma Proteobacteria, and that these lineages have undergone pronounced genome reduction. A new genus and species name, 'Candidatus Baumannia cicadellinicola' (sp. nov.) is proposed for this newly characterized clade of symbiotic bacteria.

Animals↗
PubMed2002

Type III secretion systems and the evolution of mutualistic endosymbiosis.

The view that parasites can develop cooperative symbiotic relationships with their hosts is both appealing and widely held; however, there is no molecular genetic evidence of such a transition. Here we demonstrate that a mutualistic bacterial endosymbiont of grain weevils maintains and expresses inv/spa genes encoding a type III secretion system homologous to that used for invasion by bacterial pathogens. Phylogenetic analyses indicate that inv/spa genes were present in presymbiotic ancestors of the weevil endosymbionts, occurring at least 50 million years ago. The function of inv/spa genes in maintaining symbiosis is demonstrated by the up-regulation of their expression under both in vivo and in vitro conditions that coincide with host cell invasion.

Adhesins, Bacterial↗
PubMed2002

Bacterial evolution: chromosome arithmetic and geometry.

Recent sequencing projects have characterized bacterial genomes that are organized onto elements of various sizes, shapes and numbers. Aside from its biological relevance and curiosity, this diversity calls into question the way that we define bacterial chromosomes.

Bacteria↗
PubMed2002

Distinguishing the ORFs from the ELFs: short bacterial genes and the annotation of genomes.

A substantial fraction of hypothetical open reading frames (ORFs) in completely sequenced bacterial genomes are short, suggesting that many are not genes but random stretches of DNA. Although it is not feasible to authenticate the coding capacity of all such regions experimentally, comparisons of ORFs in related genomes can expose those that encode functional proteins.

Bacteria↗
PubMed2002

Effect of chromosome location on bacterial mutation rates.

In previous comparisons of enterobacterial sequences, synonymous substitution rates were higher in genes closer to the replication terminus, suggesting that mutation rates increase with distance from the replication origin. In order to directly test for the effects of chromosomal location on the rates of point mutations, we assayed the reversion rates of two lacZ alleles inserted at four positions in the Salmonella enterica chromosome. Mutation rates at an intermediate locus were significantly higher than those at loci nearer to and farther from the replication origin. The higher reversion rates at this locus were neither the result of an overall increase in mutation rates produced by the insertion at this location nor a function of the mutations' immediate neighbors, but rather a regional effect. At all loci, regardless of chromosome location, T.A --> G.C transversions were more frequent than A.T --> G.C transitions during the exponential phase.

Analysis of Variance↗
PubMed2002

Gene location and bacterial sequence divergence.

Previous comparison of a relatively small set of homologous genes from Escherichia coli and Salmonella typhimurium revealed that genes nearer to the origin of replication had substitution rates lower than genes closer to the replication terminus. The recently completed sequences of numerous bacterial genomes have allowed us to test whether this effect of distance from the replication origin on substitution rates, as observed for the E. coli-S. typhimurium comparison, is a general feature of bacterial genomes. Extending the analysis to all 3,000 E. coli-S. typhimurium homologs confirmed the significant association between chromosomal position and synonymous site divergence. However, the effect, though still significant, is not as dramatic as originally thought. A similar association between relative chromosomal location and synonymous substitution rate was detected in the majority of other bacterial species comparisons within alpha- and gamma- Proteobacteria, and Firmicutes but was absent in Chlamydiales. The opposite trend, i.e., a decrease in synonymous divergence with distance from the replication origin, was detected in Mycobacteria. Analysis of the patterns of nucleotide substitutions revealed that the distance effect is not affected by gene orientation and is mainly caused by an increase in rates of transversions, suggesting that this effect may not be caused by recombinational repair or biased gene conversion, as originally suggested.

Bacteria↗