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H Ochman

Publications and source records attributed to H Ochman.

At least 19 recordsLinked to original sources
PubMed1997

Amelioration of bacterial genomes: rates of change and exchange.

Although bacterial species display wide variation in their overall GC contents, the genes within a particular species' genome are relatively similar in base composition. As a result, sequences that are novel to a bacterial genome-i.e., DNA introduced through recent horizontal transfer-often bear unusual sequence characteristics and can be distinguished from ancestral DNA. At the time of introgression, horizontally transferred genes reflect the base composition of the donor genome; but, over time, these sequences will ameliorate to reflect the DNA composition of the new genome because the introgressed genes are subject to the same mutational processes affecting all genes in the recipient genome. This process of amelioration is evident in a large group of genes involved in host-cell invasion by enteric bacteria and can be modeled to predict the amount of time required after transfer for foreign DNA to resemble native DNA. Furthermore, models of amelioration can be used to estimate the time of introgression of foreign genes in a chromosome. Applying this approach to a 1.43-megabase continuous sequence, we have calculated that the entire Escherichia coli chromosome contains more than 600 kb of horizontally transferred, protein-coding DNA. Estimates of amelioration times indicate that this DNA has accumulated at a rate of 31 kb per million years, which is on the order of the amount of variant DNA introduced by point mutations. This rate predicts that the E. coli and Salmonella enterica lineages have each gained and lost more than 3 megabases of novel DNA since their divergence.

Bacteria↗
PubMed1997

Strand asymmetries in DNA evolution.

The complementary strands of DNA differ with respect to replication and transcription. Both of these processes are asymmetric and can bias the occurrence of mutations between the strands: during replication, the discontinuous lagging strand undergoes certain errors at higher rates, and transcription overexposes the nontranscribed strand to DNA damage while targeting repair enzymes to the transcribed strand. While biases introduced during replication apparently have little impact on sequence evolution, the effects of transcription are observed in the asymmetric patterns of substitution in bacterial genes and might be influencing genome-wide patterns of base composition.

DNA↗
PubMed1997

How Salmonella became a pathogen.

In many pathogens, virulence can be conferred by a single region of the genome. In contrast, the facultative intracellular lifestyle of Salmonella demands a large number of genes distributed around the chromosome. The evolution of Salmonella has been marked by the acquisition of several 'pathogenicity islands', each contributing to the unique virulence properties of this microorganism.

Chromosome Mapping↗
PubMed1997

Miles of isles.

Explore the source record for details and available documents.

Bacterial Proteins↗
PubMed1997

Comparative genetics of the inv-spa invasion gene complex of Salmonella enterica.

The chromosomal region containing the Salmonella enterica pathogenic island inv-spa was present in the last common ancestor of all the contemporary lineages of salmonellae. For multiple strains of S. enterica, representing all eight subspecies, nucleotide sequences were obtained for five genes of the inv-spa invasion complex, invH, invE, invA, spaM, and spaN, al of which encode proteins that are required for entry of the bacteria into cultured epithelial cells. The invE, invA, spaM, and spaN genes were present in all eight subspecies of S. enterica, and for invE and invA and their products, levels of sequence variation among strains were within the ranges reported for housekeeping genes. In contrast, the InvH, SpaM, and SpaN proteins were unusually variable in amino acid sequence. Furthermore, invH was absent from the subspecies V isolates examined. The SpaM and SpaN proteins provide further evidence of a relationship (first detected by Li et al. [J. Li, H. Ochman, E. A. Groisman, E. F. Boyd, F. Solomon, K. Nelson, and R. K. Selander, Proc. Natl. Acad. Sci. USA 92:7252-7256, 1995]) between the cellular location of the products of the inv-spa genes and evolutionary rate, as reflected in the level of polymorphism within S. enterica. Invasion proteins that are membrane bound or membrane associated are relatively conserved in amino acid sequence, whereas those that are exported to the extracellular environment are hypervariable, possibly reflecting the action of diversifying selection.

Bacterial Proteins↗
PubMed1996

Identification of a pathogenicity island required for Salmonella survival in host cells.

We have identified a region unique to the Salmonella typhimurium chromosome that is essential for virulence in mice. This region harbors at least three genes: two (spiA and spiB) encode products that are similar to proteins found in type III secretion systems, and a third (spiR) encodes a putative regulator. A strain with a mutation in spiA was unable to survive within macrophages but displayed wild-type levels of epithelial cell invasion. The culture supernatants of the spi mutants lacked a modified form of flagellin, which was present in the supernatant of the wild-type strain. This suggests that the Spi secretory apparatus exports a protease, or a protein that can alter the activity of a secreted protease. The "pathogenicity island" harboring the spi genes may encode the virulence determinants that set Salmonella apart from other enteric pathogens.

Amino Acid Sequence↗
PubMed1996

Asymmetries generated by transcription-coupled repair in enterobacterial genes.

Although certain replication errors occur at different frequencies on each of the complementary strands of DNA, it remains unclear whether this bias is prevalent enough during chromosome replication to affect sequence evolution. Here, nucleotide substitutions in enteric bacteria were examined, and no difference in mutation rates was detected between the leading and lagging strands, but in comparing the coding and noncoding strands, and excess of C-->T changes was observed on the coding strand. This asymmetry is best explained by transcription-coupled repair on the noncoding strand. Although the vast majority of mutations are thought to arise from spontaneous errors during replication, this result implicates DNA damage as a substantial source of mutations in the wild.

Chromosome Mapping↗
PubMed1996

Distribution of pathogenicity islands in Salmonella spp.

We investigated the phylogenetic distribution of the SPI-1 and SPI-2 pathogenicity islands in Salmonella spp. SPI-1 was present in representatives of all eight subspecific groups, but no SPI-2-hybridizing sequences were detected in group V (S. bongori). Our data suggest that SPI-2 was acquired by S. enterica after its split from S. bongori.

Phylogeny↗
PubMed1995

Relationship between evolutionary rate and cellular location among the Inv/Spa invasion proteins of Salmonella enterica.

For 21 strains of Salmonella enterica, nucleotide sequences were obtained for three invasion genes, spaO, spaP, and spaQ, of the chromosomal inv/spa complex, the products of which form a protein export system required for entry of the bacteria into nonphagocytic host cells. These genes are present in all eight subspecies of the salmonellae, and homologues occur in a variety of other bacteria, including the enteric pathogens Shigella and Yersinia, in which they are plasmid borne. Evolutionary diversification of the invasion genes among the subspecies of S. enterica has been generally similar in pattern and average rate to that of housekeeping genes. However, the range of variation in evolutionary rate among the invasion genes is unusually large, and there is a relationship between the evolutionary rate and cellular location of the invasion proteins, possibly reflecting diversifying selection on exported proteins in adaptation to variable host factors in extracellular environments. The SpaO protein, which is hypervariable in S. enterica and exhibits only 24% sequence identity with its homologues in Shigella and Yersinia, is secreted. In contrast, the membrane-associated proteins SpaP, SpaQ, and InvA are weakly polymorphic and have > 60% sequence identity with the corresponding proteins of other enteric bacteria. Acquisition of the inv/spa genes may have been a key event in the evolution of the salmonellae as pathogens, following which the invention of flagellar phase shifting facilitated niche expansion to include warm-blooded vertebrates.

Adhesins, Bacterial↗
PubMed1995

Physical structure of human chromosome 21: an analysis of YACs spanning 21q.

We have resolved the sizes of the yeast artificial chromosomes (YACs) from an ordered library spanning the entire long arm of Chromosome (Chr) 21 to examine the proximity of sequence-tagged sites (STS) originally used to position these clones. The average insert length was 540 kilobases, and some 18% of the 765 clones have either lost or generated multiple YACs during cultivation. Comparing the sizes of YACs that share common sites allowed the identification of an additional 8% of the clones with large scale additions or deletions. Maximum physical distances between chromosome markers, as established by the co-occurrence of STS on a single YAC, generally agreed with those estimated by other procedures, except for a large region in 21q21. In addition to providing insights into the structure, mapping and organization of this chromosome, knowledge of the sizes and contents of these clones will greatly facilitate the acquisition of any sequence present in this library.

Chromosome Mapping↗
PubMed1995

Genome evolution in enteric bacteria.

For more than a decade, the study of bacterial evolution has been dominated by the comparative analysis of nucleotide sequences within and among species. This approach, combined with the characterization of extensive regions of the chromosome by pulsed-field gel electrophoresis, has led to new insights into the dynamics of bacterial genomes.

Biological Evolution↗
PubMed1995

Heterogeneity of genome sizes among natural isolates of Escherichia coli.

Comparisons of the genetic maps of Escherichia coli K-12 and Salmonella typhimurium LT2 suggest that the size and organization of bacterial chromosomes are highly conserved. Employing pulsed-field gel electrophoresis, we have estimated the extent of variation in genome size among 14 natural isolates of E. coli. The BlnI and NotI restriction fragment patterns were highly variable among isolates, and genome sizes ranged from 4,660 to 5,300 kb, which is several hundred kilobases larger than the variation detected between enteric species. Genome size differences increase with the evolutionary genetic distance between lineages of E. coli, and there are differences in genome size among the major subgroups of E. coli. In general, the genomes of natural isolates are larger than those of laboratory strains, largely because of the fact that laboratory strains were derived from the subgroup of E. coli with the smallest genomes.

Biological Evolution↗
PubMed1995

The evolution of invasion by enteric bacteria.

Despite differences in disease pathologies and host range, many enteric pathogens, including Salmonella and Shigella spp., utilize a remarkably similar machinery to secrete proteins that promote their entry into host cells. Analogous structures are required for the export of virulence proteins in other animal and plant pathogens. While the structure and organization of the gene complexes specifying these secretory pathways are broadly conserved, their phylogenetic distribution and genomic locations suggest that these sequences arose independently in divergent pathogens.

Antigens, Bacterial↗
PubMed1994

The origin and evolution of species differences in Escherichia coli and Salmonella typhimurium.

Since diverging from a common ancestor some 120 million years, Escherichia coli and Salmonella typhimurium have accumulated numerous phenotypic characteristics which have traditionally been used to distinguish these enteric species. While most of the genetic differences between these species are due to the accumulation of point mutations, the majority of the observed variation in phenotypic characters is attributable to segments of the genome confined to only one of the species. We have analyzed the map positions, G+C contents, nucleotide sequences and functions of regions unique to the Salmonella chromosome in an attempt to determine the ancestry of species-specific sequences. Some of the Salmonella-specific regions had uncharacteristically low base compositions and contained open reading frames of atypical codon usage patterns suggesting that portions of the genome were acquired by horizontal transfer from distantly-related bacterial species. The role of these species-specific sequences was assayed by constructing mutant strains harboring deletions in the corresponding regions of the genome. Several functions were ascribed to these unique portions of the Salmonella chromosome, including one encoding proteins involved in virulence and invasion of host epithelial cells.

Biological Evolution↗
PubMed1994

How to become a pathogen.

For most bacterial species, virulence is viewed as a derived state, whereby pathogens acquire certain loci and are rendered virulent. The majority of virulence genes in Salmonella are present in closely related nonpathogenic species, and most genes known to be confined to the salmonellae are not essential for virulence. Alternative evolutionary scenarios may explain the origins of pathogenicity in Salmonella.

Alleles↗