The chromosomal origin and terminus of replication are precisely localized in bacterial cells. We examined the cellular position of 112 individual loci that are dispersed over the circular Caulobacter crescentus chromosome and found that in living cells each locus has a specific subcellular address and that these loci are arrayed in linear order along the long axis of the cell. Time-lapse microscopy of the location of the chromosomal origin and 10 selected loci in the origin-proximal half of the chromosome showed that during DNA replication, as the replisome sequentially copies each locus, the newly replicated DNA segments are moved in chronological order to their final subcellular destination in the nascent half of the predivisional cell. Thus, the remarkable organization of the chromosome is being established while DNA replication is still in progress. The fact that the movement of these 10 loci is, like that of the origin, directed and rapid, and occurs at a similar rate, suggests that the same molecular machinery serves to partition and place many, if not most, chromosomal loci at defined subcellular sites. Bacterial chromosomes are not static structures. They undergo dynamic topological changes during DNA replication, segregation, and transcription (1-5). For bacteria with circular chromosomes, replication initiates at a single origin of replication (ori) and proceeds bidirectionally toward the terminus of replication (ter) (6). During replication, the DNA double helix is unwound locally, introducing compensatory superhelicity and entanglements that are relieved by the action of topoisomerases (1). Before newly replicated DNA can be segregated, the two sister chromosomes are unlinked by topoisomerases, resolvases, and recombinases (2,7,8). After the completion of replication and segregation, each half of the predivisional cell contains one sister chromosome. The mechanism whereby the chromosomes are moved, positioned, and finally restructured before cell division is poorly understood.Fluorescence in situ hybridization (FISH) has been used to visualize distinct chromosomal loci in fixed bacterial cells (9). In addition, a technique to label chromosomal loci in live cells has been developed by using a lac repressor GFP hybrid protein (LacI-GFP) that binds to arrays of lac operator (lacO) sequences inserted at specific sites on the chromosome (10-12). By using this labeling technique along with time-lapse fluorescence microscopy (FM), both the Escherichia coli and the Bacillus subtilis ori have been shown to move rapidly toward the cell poles once DNA replication has initiated (13-15).Chromosome replication and segregation is coordinated with other events during the cell cycle, such as polar morphogenesis and cell division. In Caulobacter, DNA replication initiates once and only once per cell cycle and proceeds bidirectionally from a single origin (16,17). Caulobacter cell division is asymmetric, yielding a replicative stalked cell and a nonreplicative swarmer cell with polar pili and a polar flagellum (18)(19...

Most heritable behavioral traits have a complex genetic basis, but few multigenic traits are understood at a molecular level. Here we show that the C. elegans strains N2 and CB4856 have opposite behavioral responses to simultaneous changes in environmental O2 and CO2. We identify two quantitative trait loci (QTL) that affect this trait, and map each QTL to a single-gene polymorphism. One gene, npr-1, encodes a previously described neuropeptide receptor whose high activity in N2 promotes CO2 avoidance. The second gene, glb-5, encodes a neuronal globin domain protein whose high activity in CB4856 modifies behavioral responses to O2 and combined O2/CO2 stimuli. glb-5 acts in O2–sensing neurons to increase O2-evoked calcium signals, implicating globins in sensory signaling. An analysis of wild C. elegans strains indicates that the N2 alleles of npr-1 and glb-5 arose recently in the same strain background, possibly as an adaptation to laboratory conditions.

Temporally and spatially controlled master regulators drive the Caulobacter cell cycle by regulating the expression of >200 genes. Rapid clearance of the master regulator, CtrA, by the ClpXP protease is a critical event that enables the initiation of chromosome replication at specific times in the cell cycle. We show here that a previously unidentified single domain-response regulator, CpdR, when in the unphosphorylated state, binds to ClpXP and, thereby, causes its localization to the cell pole. We further show that ClpXP localization is required for CtrA proteolysis. When CpdR is phosphorylated, ClpXP is delocalized, and CtrA is not degraded. Both CtrA and CpdR are phosphorylated via the same CckA histidine kinase phospho-signaling pathway, providing a reinforcing mechanism that simultaneously activates CtrA and prevents its degradation by delocalizing the CpdR͞ClpXP complex. In swarmer cells, CpdR is in the phosphorylated state, thus preventing ClpXP localization and CtrA degradation. As swarmer cells differentiate into stalked cells (G1͞S transition), unphosphorylated CpdR accumulates and is localized to the stalked cell pole, where it enables ClpXP localization and CtrA proteolysis, allowing the initiation of DNA replication. Dynamic protease localization mediated by a phosphosignaling pathway is a novel mechanism to integrate spatial and temporal control of bacterial cell cycle progression.Caulobacter ͉ ClpXP ͉ phosphorylation ͉ proteolysis ͉ temporal control

Evolution can follow predictable genetic trajectories1, indicating that discrete environmental shifts can select for reproducible genetic changes2-4. Conspecific individuals are an important feature of an animal's environment, and a potential source of selective pressures. We show here that adaptation of two Caenorhabditis species to growth at high density, a feature common to domestic environments, occurs by reproducible genetic changes to pheromone receptor genes. Chemical communication through pheromones that accumulate during high-density growth causes young nematode larvae to enter the long-lived but non-reproductive dauer stage. Two strains of Caenorhabditis elegans grown at high density have independently acquired multigenic resistance to pheromone-induced dauer formation. In each strain, resistance to the pheromone ascaroside C3 results from a deletion that disrupts the adjacent chemoreceptor genes serpentine receptor class g (srg)-36 and -37. Through misexpression experiments, we show that these genes encode redundant G protein-coupled receptors for ascaroside C3. Multigenic resistance to dauer formation has also arisen in high-density cultures of a different nematode species, Caenorhabditis briggsae, resulting in part from deletion of an srg gene paralogous to srg-36 and srg-37. These results demonstrate rapid remodeling of the chemoreceptor repertoire as an adaptation to specific environments, and indicate that parallel changes to a common genetic substrate can affect life history traits across species.