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Biomedical subjects

H Ochman

Publications and source records attributed to H Ochman.

At least 19 recordsLinked to original sources

Genes lost and genes found: evolution of bacterial pathogenesis and symbiosis.

Traditionally, evolutionary biologists have viewed mutations within individual genes as the major source of phenotypic variation leading to adaptation through natural selection, and ultimately generating diversity among species. Although such processes must contribute to the initial development of gene functions and their subsequent fine-tuning, changes in genome repertoire, occurring through gene acquisition and deletion, are the major events underlying the emergence and evolution of bacterial pathogens and symbionts. Furthermore, pathogens and symbionts depend on similar mechanisms for interacting with hosts and show parallel trends in genome evolution.

Animals↗

Deletional bias and the evolution of bacterial genomes.

Although bacteria increase their DNA content through horizontal transfer and gene duplication, their genomes remain small and, in particular, lack nonfunctional sequences. This pattern is most readily explained by a pervasive bias towards higher numbers of deletions than insertions. When selection is not strong enough to maintain them, genes are lost in large deletions or inactivated and subsequently eroded. Gene inactivation and loss are particularly apparent in obligate parasites and symbionts, in which dramatic reductions in genome size can result not from selection to lose DNA, but from decreased selection to maintain gene functionality. Here we discuss the evidence showing that deletional bias is a major force that shapes bacterial genomes.

Bacteria↗

Evolutionary dynamics of full genome content in Escherichia coli.

The evolutionary history of the entire Escherichia coli chromosome was traced by examining the distribution of the approximately 4300 open reading frames (ORFs) from E.coli MG1655 among strains of known genealogical relationships. Using this framework to deduce the incidence of gene transfer and gene loss, a total of 67 events-37 additions and 30 deletions-were required to account for the distribution of all genes now present in the MG1655 chromosome. Nearly 90% of the ORFs were common to all strains examined, but, given the variation in gene content and chromosome size, strains can contain well over a megabase of unique DNA, conferring traits that distinguish them from other members of the species. Moreover, strains vary widely in their frequencies of deletions, which probably accounts for the variation in genome size within the species.

Escherichia coli↗

Lateral gene transfer and the nature of bacterial innovation.

Unlike eukaryotes, which evolve principally through the modification of existing genetic information, bacteria have obtained a significant proportion of their genetic diversity through the acquisition of sequences from distantly related organisms. Horizontal gene transfer produces extremely dynamic genomes in which substantial amounts of DNA are introduced into and deleted from the chromosome. These lateral transfers have effectively changed the ecological and pathogenic character of bacterial species.

Bacteria↗

Strand symmetry around the beta-globin origin of replication in primates.

Certain mutations are known to occur with differing frequencies on the leading and lagging strands of DNA. The extent to which these mutational biases affect the sequences of higher eukaryotes has been difficult to ascertain because the positions of most replication origins are not known, making it impossible to distinguish between the leading and lagging strands. To resolve whether strand biases influence the evolution of primate sequences, we compared the substitution patterns in noncoding regions adjacent to an origin of replication identified within the beta-globin complex. Although there was limited asymmetry around the beta-globin origin of replication, patterns of substitutions do not support the existence of a mutational bias between the leading and lagging strands of chromosomal DNA replication in primates.

Animals↗

Long-term shifts in patterns of antibiotic resistance in enteric bacteria.

Several mechanisms are responsible for the ability of microorganisms to tolerate antibiotics, and the incidence of resistance to these compounds within bacterial species has increased since the commercial use of antibiotics became widespread. To establish the extent of and changes in the diversity of antibiotic resistance patterns in natural populations, we determined the MICs of five antibiotics for collections of enteric bacteria isolated from diverse hosts and geographic locations and during periods before and after commercial application of antibiotics began. All of the pre-antibiotic era strains were susceptible to high levels of these antibiotics, whereas 20% of strains from contemporary populations of Escherichia coli and Salmonella enterica displayed high-level resistance to at least one of the antibiotics. In addition to the increase in the frequency of high-level resistance, background levels, conferred by genes providing nonspecific low-level resistance to multiple antibiotics, were significantly higher among contemporary strains. Changes in the incidence and levels of antibiotic resistance are not confined to particular segments of the bacterial population and reflect responses to the increased exposure of bacteria to antimicrobial compounds over the past several decades.

Ampicillin Resistance↗

Decoupling of genome size and sequence divergence in a symbiotic bacterium.

In contrast to genome size variation in most bacterial taxa, the small genome size of Buchnera sp. was shown to be highly conserved across genetically diverse isolates (630 to 643 kb). This exceptional size conservation may reflect the inability of this obligate mutualist to acquire foreign DNA and reduced selection for genetic novelty within a static intracellular environment.

Animals↗

Calibrating bacterial evolution.

Attempts to calibrate bacterial evolution have relied on the assumption that rates of molecular sequence divergence in bacteria are similar to those of higher eukaryotes, or to those of the few bacterial taxa for which ancestors can be reliably dated from ecological or geological evidence. Despite similarities in the substitution rates estimated for some lineages, comparisons of the relative rates of evolution at different classes of nucleotide sites indicate no basis for their universal application to all bacteria. However, there is evidence that bacteria have a constant genome-wide mutation rate on an evolutionary time scale but that this rate differs dramatically from the rate estimated by experimental methods.

Bacteria↗

Bacterial evolution: Jittery genomes.

Recent studies of long-term experimental populations of bacteria have revealed the actual progression of evolutionary change and how rates of phenotypic evolution can be decoupled from rates of genomic evolution.

Biological Evolution↗

Chromosomal changes during experimental evolution in laboratory populations of Escherichia coli.

Short-term rates of chromosome evolution were analyzed in experimental populations of Escherichia coli B that had been propagated for 2,000 generations under four thermal regimens. Chromosome alterations were monitored in 24 independent populations by pulsed-field gel electrophoresis of DNA treated with five rare-cutting restriction enzymes. A total of 11 changes, 8 affecting chromosome size and 3 altering restriction sites, were observed in these populations, with none occurring in strains cultured at 37 degreesC. Considering the changes detected in these experimental populations, the rate of chromosome alteration of E. coli is estimated to be half of that observed in experimental populations of yeast.

Biological Evolution↗

Molecular archaeology of the Escherichia coli genome.

The availability of the complete sequence of Escherichia coli strain MG1655 provides the first opportunity to assess the overall impact of horizontal genetic transfer on the evolution of bacterial genomes. We found that 755 of 4,288 ORFs (547.8 kb) have been introduced into the E. coli genome in at least 234 lateral transfer events since this species diverged from the Salmonella lineage 100 million years (Myr) ago. The average age of introduced genes was 14.4 Myr, yielding a rate of transfer 16 kb/Myr/lineage since divergence. Although most of the acquired genes subsequently were deleted, the sequences that have persisted ( approximately 18% of the current chromosome) have conferred properties permitting E. coli to explore otherwise unreachable ecological niches.

Chromosomes, Bacterial↗

Rates and patterns of chromosome evolution in enteric bacteria.

Although several types of large-scale alterations potentially affect the structure and organization of bacterial genomes, recent analyses of physical maps and complete genomic sequences reveal that chromosome heterogeneity in enteric bacteria has resulted from the acquisition and deletion of large segments of DNA. These acquired sequences can provide novel functions immediately upon their introduction and play a significant role in the diversification of bacterial species.

Biological Evolution↗

Distribution of chromosome length variation in natural isolates of Escherichia coli.

Large-scale variation in chromosome size was analyzed in 35 natural isolates of Escherichia coli by physical mapping with a restriction enzyme whose sites are restricted to rDNA operons. Although the genetic maps and chromosome lengths of the laboratory strains E. coli K12 and Salmonella enterica sv. Typhimurium LT2 are highly congruent, chromosome lengths among natural strains of E. coli can differ by as much as 1 Mb, ranging from 4.5 to 5.5 Mb in length. This variation has been generated by multiple changes dispersed throughout the genome, and these alterations are correlated; i.e., additions to one portion of the chromosome are often accompanied by additions to other chromosomal regions. This pattern of variation is most probably the result of selection acting to maintain equal distances between the replication origin and terminus on each side of the circular chromosome. There is a large phylogenetic component to the observed size variation: natural isolates from certain subgroups of E. coli have consistently larger chromosome, suggesting that much of the additional DNA in larger chromosomes is shared through common ancestry. There is no significant correlation between genome sizes and growth rates, which counters the view that the streamlining of bacterial genomes is a response to selection for faster growth rates in natural populations.

Chromosome Mapping↗

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↗

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↗