Shifts in growth strategies reflect tradeoffs in cellular economics

The growth rate-dependent regulation of cell size, ribosomal content, and metabolic efficiency follows a common pattern in unicellular organisms: with increasing growth rates, cell size and ribosomal content increase and a shift to energetically inefficient metabolism takes place. The latter two phenomena are also observed in fast growing tumour cells and cell lines. These patterns suggest a fundamental principle of design. In biology such designs can often be understood as the result of the optimization of fitness. Here we show that in basic models of self-replicating systems these patterns are the consequence of maximizing the growth rate. Whereas most models of cellular growth consider a part of physiology, for instance only metabolism, the approach presented here integrates several subsystems to a complete self-replicating system. Such models can yield fundamentally different optimal strategies. In particular, it is shown how the shift in metabolic efficiency originates from a tradeoff between investments in enzyme synthesis and metabolic yields for alternative catabolic pathways. The models elucidate how the optimization of growth by natural selection shapes growth strategies

A map of specific cleavage sites and tRNA genes in the chloroplast genome of Euglena gracilis bacillaris

A map showing locations of 22 of the 30 endonuclease EcoRI cleavage sites and 54 additional sites for eight other restriction endonucleases is presented. The regions of chloroplast DNA that hybridize with chloroplast tRNA are also shown.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47547/1/438_2004_Article_BF00425601.pd

Microbial laboratory evolution in the era of genome-scale science

Advances in DNA sequencing, high-throughput technologies, and genetic manipulation systems have enabled empirical studies of the molecular and genomic bases of adaptive evolution. This review discusses key insights learned from direct observation of the evolution process

Structure and rearrangements of rRNA genes in chloroplast DNA in two strains of Euglena gracilis

The organisation of the rRNA genes in the chloroplast genomes of two strains of Euglena gracilis were analyzed and compared. It was previously shown that the bacillaris strain contains three complete rrn (rRNA) operons (7) and that the Z-S strain contains one operon (21). Using heteroduplex analysis it was found that the bacillaris strain contains, apart from the three complete rrn operons, an extra 16S rRNA gene, an extra partial 23S rRNA gene sequence and an inverted duplication of a stretch within the 5S–16S spacer. In addition a short (<100 bp) inverted repeat sequence (13) which forms a stem/loop structure in single-stranded cpDNA was located between the 3′-end of the extra 16S rRNA gene and the partial 23 S rRNA sequence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43440/1/11103_2004_Article_BF00016060.pd

Recombination-induced suppression of cell division following P1-mediated generalized transduction in Klebsiella aerogenes

Klebsiella aerogenes recombinants resulting from bacteriophage P1-mediated generalized transduction failed to increase in number for approximately six generations after transduction. Nevertheless these recombinants continued to grow and became sensitive to penicillin after a transient resistance, suggesting that the cells were growing as long, non-dividing filaments. When filamentous cells were isolated from transduced cultures by gradient centrifugation, recombinants were 1000-fold more frequent among the filaments than among the normal-sized cells. The suppression of cell-division lasted for six generations whether markers near the origin ( gln, ilv ) or terminus ( his, trp ) of chromosome replication were used, despite a 50-fold difference in transduction frequencies for these markers. The suppression of cell division was a host response to recombination rather than to P1 invasion since cells lysogenized by P1 in these same experiments showed only a short (two generation) suppression of cell division. We speculate that the suppression of cell-division is an SOS response triggered by the degraded DNA not incorporated in the final recombinant. We demonstrate that both the filamentation and the transient penicillin resistance of recombinant cells can be exploited to enrich greatly for recombinants, raising transduction frequencies to as high as 10 -3 .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47551/1/438_2004_Article_BF00337815.pd

Achieving Optimal Growth through Product Feedback Inhibition in Metabolism

Recent evidence suggests that the metabolism of some organisms, such as Escherichia coli, is remarkably efficient, producing close to the maximum amount of biomass per unit of nutrient consumed. This observation raises the question of what regulatory mechanisms enable such efficiency. Here, we propose that simple product-feedback inhibition by itself is capable of leading to such optimality. We analyze several representative metabolic modules—starting from a linear pathway and advancing to a bidirectional pathway and metabolic cycle, and finally to integration of two different nutrient inputs. In each case, our mathematical analysis shows that product-feedback inhibition is not only homeostatic but also, with appropriate feedback connections, can minimize futile cycling and optimize fluxes. However, the effectiveness of simple product-feedback inhibition comes at the cost of high levels of some metabolite pools, potentially associated with toxicity and osmotic imbalance. These large metabolite pool sizes can be restricted if feedback inhibition is ultrasensitive. Indeed, the multi-layer regulation of metabolism by control of enzyme expression, enzyme covalent modification, and allostery is expected to result in such ultrasensitive feedbacks. To experimentally test whether the qualitative predictions from our analysis of feedback inhibition apply to metabolic modules beyond linear pathways, we examine the case of nitrogen assimilation in E. coli, which involves both nutrient integration and a metabolic cycle. We find that the feedback regulation scheme suggested by our mathematical analysis closely aligns with the actual regulation of the network and is sufficient to explain much of the dynamical behavior of relevant metabolite pool sizes in nutrient-switching experiments

Niche Occupation Limits Adaptive Radiation in Experimental Microcosms

Adaptive radiations have played a key role in the evolution of biological diversity. The breadth of adaptive radiation in an invading lineage is likely to be influenced by the availability of ecological niches, which will be determined to some extent by the diversity of the resident community. High resident diversity may result in existing ecological niches being filled, inhibiting subsequent adaptive radiation. Conversely, high resident diversity could result in the creation of novel ecological niches or an increase in within niche competition driving niche partitioning, thus promoting subsequent diversification. We tested the role of resident diversity on adaptive radiations in experimental populations of the bacterium Pseudomonas fluorescens that readily diversify into a range of niche specialists when grown in a heterogeneous environment. We allowed an undiversified strain to invade resident communities that varied in the number of niche specialists. The breadth of adaptive radiation attainable by an invading lineage decreased with increasing niche occupation of the resident community. Our results highlight the importance of niche occupation as a constraint on adaptive radiation

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

The Repeatability of Adaptive Radiation During Long-Term Experimental Evolution of Escherichia coli in a Multiple Nutrient Environment

Adaptive radiations occur when a species diversifies into different ecological specialists due to competition for resources and trade-offs associated with the specialization. The evolutionary outcome of an instance of adaptive radiation cannot generally be predicted because chance (stochastic events) and necessity (deterministic events) contribute to the evolution of diversity. With increasing contributions of chance, the degree of parallelism among different instances of adaptive radiations and the predictability of an outcome will decrease. To assess the relative contributions of chance and necessity during adaptive radiation, we performed a selection experiment by evolving twelve independent microcosms of Escherichia coli for 1000 generations in an environment that contained two distinct resources. Specialization to either of these resources involves strong trade-offs in the ability to use the other resource. After selection, we measured three phenotypic traits: 1) fitness, 2) mean colony size, and 3) colony size diversity. We used fitness relative to the ancestor as a measure of adaptation to the selective environment; changes in colony size as a measure of the evolution of new resource specialists because colony size has been shown to correlate with resource specialization; and colony size diversity as a measure of the evolved ecological diversity. Resource competition led to the rapid evolution of phenotypic diversity within microcosms. Measurements of fitness, colony size, and colony size diversity within and among microcosms showed that the repeatability of adaptive radiation was high, despite the evolution of genetic variation within microcosms. Consistent with the observation of parallel evolution, we show that the relative contributions of chance are far smaller and less important than effects due to adaptation for the traits investigated. The two-resource environment imposed similar selection pressures in independent populations and promoted parallel phenotypic adaptive radiations in all independently evolved microcosms

Immunogenic Salivary Proteins of Triatoma infestans: Development of a Recombinant Antigen for the Detection of Low-Level Infestation of Triatomines

Chagas disease, caused by Trypanosoma cruzi, is a neglected disease with 20 million people at risk in Latin America. The main control strategies are based on insecticide spraying to eliminate the domestic vectors, the most effective of which is Triatoma infestans. This approach has been very successful in some areas. However, there is a constant risk of recrudescence in once-endemic regions resulting from the re-establishment of T. infestans and the invasion of other triatomine species. To detect low-level infestations of triatomines after insecticide spraying, we have developed a new epidemiological tool based on host responses against salivary antigens of T. infestans. We identified and synthesized a highly immunogenic salivary protein. This protein was used successfully to detect differences in the infestation level of T. infestans of households in Bolivia and the exposure to other triatomine species. The development of such an exposure marker to detect low-level infestation may also be a useful tool for other disease vectors