Biomedical subjects

Heike Keller

Publications and source records attributed to Heike Keller.

6 recordsLinked to original sources

PubMed2006

Who ate whom? Adaptive Helicobacter genomic changes that accompanied a host jump from early humans to large felines.

Helicobacter pylori infection of humans is so old that its population genetic structure reflects that of ancient human migrations. A closely related species, Helicobacter acinonychis, is specific for large felines, including cheetahs, lions, and tigers, whereas hosts more closely related to humans harbor more distantly related Helicobacter species. This observation suggests a jump between host species. But who ate whom and when did it happen? In order to resolve this question, we determined the genomic sequence of H. acinonychis strain Sheeba and compared it to genomes from H. pylori. The conserved core genes between the genomes are so similar that the host jump probably occurred within the last 200,000 (range 50,000-400,000) years. However, the Sheeba genome also possesses unique features that indicate the direction of the host jump, namely from early humans to cats. Sheeba possesses an unusually large number of highly fragmented genes, many encoding outer membrane proteins, which may have been destroyed in order to bypass deleterious responses from the feline host immune system. In addition, the few Sheeba-specific genes that were found include a cluster of genes encoding sialylation of the bacterial cell surface carbohydrates, which were imported by horizontal genetic exchange and might also help to evade host immune defenses. These results provide a genomic basis for elucidating molecular events that allow bacteria to adapt to novel animal hosts.

Animals↗

PubMed2006

Comprehensive mutation identification in an evolved bacterial cooperator and its cheating ancestor.

Precise characterization of the mutation histories of evolutionary lineages is crucial for understanding the evolutionary process, yet mutation identification has been constrained by traditional techniques. We sought to identify all accumulated mutations in an experimentally evolved lineage of the cooperative bacterium Myxococcus xanthus, which constructs fruiting bodies by a process of social multicellular development in response to starvation. This lineage had undergone two major transitions in social phenotype: from an ancestral cooperator to a socially defective cheater, and from the cheater to a competitively dominant cooperator that re-evolved social and developmental proficiency. The 9.14-Mb genome of the evolved, dominant cooperator (strain "PX") was sequenced to approximately 19-fold coverage by using recent "sequencing-by-synthesis" technology and partially sequenced (approximately 45%) by using capillary technology. The resulting data revealed 15 single-nucleotide mutations relative to the laboratory ancestor of PX after the two phases of experimental evolution but no evidence of duplications, transpositions, or multiple-base deletions. No mutations were identified by capillary sequencing beyond those found by pyrosequencing, resulting in a high probability that all mutations were discovered. Seven errors in the reference strain previously sequenced by the Sanger approach were revealed, as were five mutational differences between two distinct laboratory stocks of the reference strain. A single mutation responsible for the restoration of development in strain PX was identified, whereas 14 mutations occurred during the prior phase of experimental evolution. These results provide insight into the genetic basis of two large adaptive transitions in a social bacterium.

Adaptation, Biological↗

PubMed2004

A predator unmasked: life cycle of Bdellovibrio bacteriovorus from a genomic perspective.

Predatory bacteria remain molecularly enigmatic, despite their presence in many microbial communities. Here we report the complete genome of Bdellovibrio bacteriovorus HD100, a predatory Gram-negative bacterium that invades and consumes other Gram-negative bacteria. Its surprisingly large genome shows no evidence of recent gene transfer from its prey. A plethora of paralogous gene families coding for enzymes, such as hydrolases and transporters, are used throughout the life cycle of B. bacteriovorus for prey entry, prey killing, and the uptake of complex molecules.

Adenosine Triphosphate↗

PubMed2003

Complete genome sequence and analysis of Wolinella succinogenes.

To understand the origin and emergence of pathogenic bacteria, knowledge of the genetic inventory from their nonpathogenic relatives is a prerequisite. Therefore, the 2.11-megabase genome sequence of Wolinella succinogenes, which is closely related to the pathogenic bacteria Helicobacter pylori and Campylobacter jejuni, was determined. Despite being considered nonpathogenic to its bovine host, W. succinogenes holds an extensive repertoire of genes homologous to known bacterial virulence factors. Many of these genes have been acquired by lateral gene transfer, because part of the virulence plasmid pVir and an N-linked glycosylation gene cluster were found to be syntenic between C. jejuni and genomic islands of W. succinogenes. In contrast to other host-adapted bacteria, W. succinogenes does harbor the highest density of bacterial sensor kinases found in any bacterial genome to date, together with an elaborate signaling circuitry of the GGDEF family of proteins. Because the analysis of the W. succinogenes genome also revealed genes related to soil- and plant-associated bacteria such as the nif genes, W. succinogenes may represent a member of the epsilon proteobacteria with a life cycle outside its host.

Bacterial Proteins↗

PubMed2003

Proteome analysis of the thermoreceptive pit membrane of the western diamondback rattlesnake Crotalus atrox.

Rattlesnakes detect their prey's temperature by means of a cavern-like structure, the pit organ. The sensory component of this organ lies within a thin membrane called the pit membrane. Proteome analysis conducted on this neurosensory tissue revealed only a relatively small number of proteins, thereby depicting its high degree of specialization. In addition to containing blood serum and structural proteins, the proteome of this membrane appears to be strikingly similar to that of isolated rattlesnake brain mitochondria. Indeed, our results show that over 80% of the detected tissue proteins are of mitochondrial origin. Fluorescence microscopy studies of these organelles indicate their dense arrangement and accumulation in structures which have been previously reported to be the terminal ends of free nerve fibers of the innervating trigeminal branches. Thus, original ultrastructural observations are paralleled by our findings at the molecular level.

Amino Acid Sequence↗

PubMed2002

A bacterial artificial chromosome-based genetic linkage map of the nematode Pristionchus pacificus.

To understand the evolution of developmental processes, nonmodel organisms in the nematodes, insects, and vertebrates are compared with established model systems. Often, these comparisons suffer from the inability to apply sophisticated technologies to these nonmodel species. In the nematode Pristionchus pacificus, cellular and genetic analyses are used to compare vulva development to that of Caenorhabditis elegans. However, substantial changes in gene function between P. pacificus and C. elegans limit the use of candidate gene approaches in studying P. pacificus mutations. To facilitate map-based cloning of mutations in P. pacificus, we constructed a BAC-based genetic linkage map. A BAC library of 13,440 clones was generated and completely end sequenced. By comparing BAC end and EST sequences between the "wild-type" strain P. pacificus var. California and the polymorphic strain P. pacificus var. Washington, 133 single-stranded conformational polymorphisms were identified. These markers were tested on a meiotic mapping panel of 46 randomly picked F(2) animals after a cross of the two strains, providing the first genetic linkage map of P. pacificus. A mapping strategy using two selected markers per chromosome was devised and the efficiency of this approach was illustrated by the mapping of the Ppa-unc-1/Twitchin gene.

Animals↗