Biomedical subjects

Heather Hendrickson

Publications and source records attributed to Heather Hendrickson.

4 recordsLinked to original sources

PubMed2006

Selection for chromosome architecture in bacteria.

Bacterial chromosomes are immense polymers whose faithful replication and segregation are crucial to cell survival. The ability of proteins such as FtsK to move unidirectionally toward the replication terminus, and direct DNA translocation into the appropriate daughter cell during cell division, requires that bacterial genomes maintain an architecture for the orderly replication and segregation of chromosomes. We suggest that proteins that locate the replication terminus exploit strand-biased sequences that are overrepresented on one DNA strand, and that selection increases with decreased distance to the replication terminus. We report a generalized method for detecting these architecture imparting sequences (AIMS) and have identified AIMS in nearly all bacterial genomes. Their increased abundance on leading strands and decreased abundance on lagging strands toward replication termini are not the result of changes in mutational bias; rather, they reflect a gradient of long-term positive selection for AIMS. The maintenance of the pattern of AIMS across the genomes of related bacteria independent of their positions within individual genes suggests a well-conserved role in genome biology. The stable gradient of AIMS abundance from replication origin to terminus suggests that the replicore acts as a target of selection, where selection for chromosome architecture results in the maintenance of gene order and in the lack of high-frequency DNA inversion within replicores.

Base Sequence↗

PubMed2005

Genome evolution in bacteria: order beneath chaos.

Bacterial genomes have been viewed as collections of genes, with each gene and genome evolving more-or-less independently through the acquisition of mutational changes. This historical view has been overturned by the finding that genomes of even closely-related taxa differ widely in gene content. Yet, genomes are more than ever-shuffling collections of genes. Some genes within a genome are more transient than others, conferring a layer of phenotypic lability over a core of genotypic stability; this core decreases in size as the taxa included become increasingly diverse. In addition, some lineages no longer experience high rates of gene turnover, and gene content alters primarily through slow rates of gene loss. More importantly, the cell and molecular biology of the bacterial cell imposes constraints on chromosome composition, maintaining a stable architecture in the face of gene turnover. As a result, genomes reflect the sum of processes that introduce variability, which is then arbitrated by processes that maintain stability.

Bacteria↗

PubMed2003

Lateral gene transfer: when will adolescence end?

The scope and impact of horizontal gene transfer (HGT) in Bacteria and Archaea has grown from a topic largely ignored by the microbiological community to a hot-button issue gaining staunch supporters (on particular points of view) at a seemingly ever-increasing rate. Opinions range from HGT being a phenomenon with minor impact on overall microbial evolution and diversification to HGT being so rampant as to obfuscate any opportunities for elucidating microbial evolution - especially organismal phylogeny - from sequence comparisons. This contentious issue has been fuelled by the influx of complete genome sequences, which has allowed for a more detailed examination of this question than previously afforded. We propose that the lack of common ground upon which to formulate consensus viewpoints probably stems from the absence of answers to four critical questions. If addressed, they could clarify concepts, reject tenuous speculation and solidify a robust foundation for the integration of HGT into a framework for long-term microbial evolution, regardless of the intellectual camp in which you reside. Here, we examine these issues, why their answers shape the outcome of this debate and the progress being made to address them.

Archaea↗

PubMed2002

Amplification-mutagenesis: evidence that "directed" adaptive mutation and general hypermutability result from growth with a selected gene amplification.

When a particular lac mutant of Escherichia coli starves in the presence of lactose, nongrowing cells appear to direct mutations preferentially to sites that allow growth (adaptive mutation). This observation suggested that growth limitation stimulates mutability. Evidence is provided here that this behavior is actually caused by a standard Darwinian process in which natural selection acts in three sequential steps. First, growth limitation favors growth of a subpopulation with an amplification of the mutant lac gene; next, it favors cells with a lac(+) revertant allele within the amplified array. Finally, it favors loss of mutant copies until a stable haploid lac(+) revertant arises and overgrows the colony. By increasing the lac copy number, selection enhances the likelihood of reversion within each developing clone. This sequence of events appears to direct mutations to useful sites. General mutagenesis is a side-effect of growth with an amplification (SOS induction). The F' plasmid, which carries lac, contributes by stimulating gene duplication and amplification. Selective stress has no direct effect on mutation rate or target specificity, but acts to favor a succession of cell types with progressively improved growth on lactose. The sequence of events--amplification, mutation, segregation--may help to explain both the origins of some cancers and the evolution of new genes under selection.

Electrophoresis, Agar Gel↗