@misc{9712,
  author       = {Tugrul, Murat and Paixao, Tiago and Barton, Nicholas H and Tkačik, Gašper},
  publisher    = {Public Library of Science},
  title        = {{Other fitness models for comparison & for interacting TFBSs}},
  doi          = {10.1371/journal.pgen.1005639.s001},
  year         = {2015},
}

@misc{9719,
  abstract     = {Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.},
  author       = {Wielgoss, Sébastien and Bergmiller, Tobias and Bischofberger, Anna M. and Hall, Alex R.},
  publisher    = {Dryad},
  title        = {{Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria}},
  doi          = {10.5061/dryad.cj910},
  year         = {2015},
}

@article{1894,
  abstract     = {Background: Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the functioning of the Dsb system in epsilon-Proteobacteria, where it plays an important role in the colonization process, we studied two homologs of the main Escherichia coli Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter jejuni, the most frequently reported bacterial cause of human enteritis in the world. Methods and Results: Phylogenetic analysis suggests the horizontal transfer of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria, which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest that the two C. jejuni DsbAs play different roles in bacterial cells and have divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical role in the oxidative folding that ensures the activity of alkaline phosphatase CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA, encoded within the dsbA2-dsbB-astA operon. Conclusions: Our results show that CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated with bacterial spread and host colonization, as well as ensuring the oxidative folding of particular protein substrates. In contrast, CjDsbA2 activity does not affect the same processes and so far its oxidative folding activity has been demonstrated for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not exclusive and there is probably another protein to be identified in C. jejuni cells that acts to re-oxidize CjDsbA1. Altogether the data presented here constitute the considerable insight to the Epsilonproteobacterial Dsb systems, which have been poorly understood so far.},
  author       = {Grabowska, Anna and Wywiał, Ewa and Dunin Horkawicz, Stanislaw and Łasica, Anna and Wösten, Marc and Nagy-Staron, Anna A and Godlewska, Renata and Bocian Ostrzycka, Katarzyna and Pieńkowska, Katarzyna and Łaniewski, Paweł and Bujnicki, Janusz and Van Putten, Jos and Jagusztyn Krynicka, Elzbieta},
  journal      = {PLoS One},
  number       = {9},
  publisher    = {Public Library of Science},
  title        = {{Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA}},
  doi          = {10.1371/journal.pone.0106247},
  volume       = {9},
  year         = {2014},
}

@article{1913,
  abstract     = {Deposits of phosphorylated tau protein and convergence of pathology in the hippocampus are the hallmarks of neurodegenerative tauopathies. Thus we aimed to evaluate whether regional and cellular vulnerability patterns in the hippocampus distinguish tauopathies or are influenced by their concomitant presence. Methods: We created a heat map of phospho-tau (AT8) immunoreactivity patterns in 24 hippocampal subregions/layers in individuals with Alzheimer's disease (AD)-related neurofibrillary degeneration (n = 40), Pick's disease (n = 8), progressive supranuclear palsy (n = 7), corticobasal degeneration (n = 6), argyrophilic grain disease (AGD, n = 18), globular glial tauopathy (n = 5), and tau-astrogliopathy of the elderly (n = 10). AT8 immunoreactivity patterns were compared by mathematical analysis. Results: Our study reveals disease-specific hot spots and regional selective vulnerability for these disorders. The pattern of hippocampal AD-related tau pathology is strongly influenced by concomitant AGD. Mathematical analysis reveals that hippocampal involvement in primary tauopathies is distinguishable from early-stage AD-related neurofibrillary degeneration. Conclusion: Our data demonstrate disease-specific AT8 immunoreactivity patterns and hot spots in the hippocampus even in tauopathies, which primarily do not affect the hippocampus. These hot spots can be shifted to other regions by the co-occurrence of tauopathies like AGD. Our observations support the notion that globular glial tauopathies and tau-astrogliopathy of the elderly are distinct entities.},
  author       = {Milenković, Ivan and Petrov, Tatjana and Kovács, Gábor},
  issn         = {1420-8008},
  journal      = {Dementia and Geriatric Cognitive Disorders},
  number       = {5-6},
  pages        = {375 -- 388},
  publisher    = {Karger Publishers},
  title        = {{Patterns of hippocampal tau pathology differentiate neurodegenerative dementias}},
  doi          = {10.1159/000365548},
  volume       = {38},
  year         = {2014},
}

@article{2036,
  abstract     = { In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments. },
  author       = {Lagator, Mato and Colegrave, Nick and Neve, Paul},
  journal      = {Proceedings of the Royal Society of London Series B Biological Sciences},
  number       = {1794},
  publisher    = {Royal Society, The},
  title        = {{Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses}},
  doi          = {10.1098/rspb.2014.1679},
  volume       = {281},
  year         = {2014},
}

@article{2056,
  abstract     = {We consider a continuous-time Markov chain (CTMC) whose state space is partitioned into aggregates, and each aggregate is assigned a probability measure. A sufficient condition for defining a CTMC over the aggregates is presented as a variant of weak lumpability, which also characterizes that the measure over the original process can be recovered from that of the aggregated one. We show how the applicability of de-aggregation depends on the initial distribution. The application section is devoted to illustrate how the developed theory aids in reducing CTMC models of biochemical systems particularly in connection to protein-protein interactions. We assume that the model is written by a biologist in form of site-graph-rewrite rules. Site-graph-rewrite rules compactly express that, often, only a local context of a protein (instead of a full molecular species) needs to be in a certain configuration in order to trigger a reaction event. This observation leads to suitable aggregate Markov chains with smaller state spaces, thereby providing sufficient reduction in computational complexity. This is further exemplified in two case studies: simple unbounded polymerization and early EGFR/insulin crosstalk.},
  author       = {Ganguly, Arnab and Petrov, Tatjana and Koeppl, Heinz},
  journal      = {Journal of Mathematical Biology},
  number       = {3},
  pages        = {767 -- 797},
  publisher    = {Springer},
  title        = {{Markov chain aggregation and its applications to combinatorial reaction networks}},
  doi          = {10.1007/s00285-013-0738-7},
  volume       = {69},
  year         = {2014},
}

@article{2083,
  abstract     = {Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment.},
  author       = {Lagator, Mato and Morgan, Andrew and Neve, Paul and Colegrave, Nick},
  journal      = {Evolution},
  number       = {8},
  pages        = {2296 -- 2305},
  publisher    = {Wiley},
  title        = {{Role of sex and migration in adaptation to sink environments}},
  doi          = {10.1111/evo.12440},
  volume       = {68},
  year         = {2014},
}

@misc{9741,
  abstract     = {In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments.},
  author       = {Lagator, Mato and Colegrave, Nick and Neve, Paul},
  publisher    = {Dryad},
  title        = {{Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses}},
  doi          = {10.5061/dryad.85dn7},
  year         = {2014},
}

@misc{9747,
  abstract     = {Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment.},
  author       = {Lagator, Mato and Morgan, Andrew and Neve, Paul and Colegrave, Nick},
  publisher    = {Dryad},
  title        = {{Data from: Role of sex and migration in adaptation to sink environments}},
  doi          = {10.5061/dryad.s42n1},
  year         = {2014},
}

@article{9931,
  abstract     = {Gene duplication is important in evolution, because it provides new raw material for evolutionary adaptations. Several existing hypotheses about the causes of duplicate retention and diversification differ in their emphasis on gene dosage, subfunctionalization, and neofunctionalization. Little experimental data exist on the relative importance of gene expression changes and changes in coding regions for the evolution of duplicate genes. Furthermore, we do not know how strongly the environment could affect this importance. To address these questions, we performed evolution experiments with the TEM-1 beta lactamase gene in Escherichia coli to study the initial stages of duplicate gene evolution in the laboratory. We mimicked tandem duplication by inserting two copies of the TEM-1 gene on the same plasmid. We then subjected these copies to repeated cycles of mutagenesis and selection in various environments that contained antibiotics in different combinations and concentrations. Our experiments showed that gene dosage is the most important factor in the initial stages of duplicate gene evolution, and overshadows the importance of point mutations in the coding region.},
  author       = {Dhar, Riddhiman and Bergmiller, Tobias and Wagner, Andreas},
  issn         = {1558-5646},
  journal      = {Evolution},
  number       = {6},
  pages        = {1775--1791},
  publisher    = {Wiley},
  title        = {{Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes}},
  doi          = {10.1111/evo.12373},
  volume       = {68},
  year         = {2014},
}

@misc{9932,
  abstract     = {Gene duplication is important in evolution, because it provides new raw material for evolutionary adaptations. Several existing hypotheses about the causes of duplicate retention and diversification differ in their emphasis on gene dosage, sub-functionalization, and neo-functionalization. Little experimental data exists on the relative importance of gene expression changes and changes in coding regions for the evolution of duplicate genes. Furthermore, we do not know how strongly the environment could affect this importance. To address these questions, we performed evolution experiments with the TEM-1 beta lactamase gene in E. coli to study the initial stages of duplicate gene evolution in the laboratory. We mimicked tandem duplication by inserting two copies of the TEM-1 gene on the same plasmid. We then subjected these copies to repeated cycles of mutagenesis and selection in various environments that contained antibiotics in different combinations and concentrations. Our experiments showed that gene dosage is the most important factor in the initial stages of duplicate gene evolution, and overshadows the importance of point mutations in the coding region.},
  author       = {Dhar, Riddhiman and Bergmiller, Tobias and Wagner, Andreas},
  publisher    = {Dryad},
  title        = {{Data from: Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes}},
  doi          = {10.5061/dryad.jc402},
  year         = {2014},
}

@inproceedings{2718,
  abstract     = {Even though both population and quantitative genetics, and evolutionary computation, deal with the same questions, they have developed largely independently of each other. I review key results from each field, emphasising those that apply independently of the (usually unknown) relation between genotype and phenotype. The infinitesimal model provides a simple framework for predicting the response of complex traits to selection, which in biology has proved remarkably successful. This allows one to choose the schedule of population sizes and selection intensities that will maximise the response to selection, given that the total number of individuals realised, C = ∑t Nt, is constrained. This argument shows that for an additive trait (i.e., determined by the sum of effects of the genes), the optimum population size and the maximum possible response (i.e., the total change in trait mean) are both proportional to √C.},
  author       = {Barton, Nicholas H and Paixao, Tiago},
  booktitle    = {Proceedings of the 15th annual conference on Genetic and evolutionary computation},
  location     = {Amsterdam, Netherlands},
  pages        = {1573 -- 1580},
  publisher    = {ACM},
  title        = {{Can quantitative and population genetics help us understand evolutionary computation?}},
  doi          = {10.1145/2463372.2463568},
  year         = {2013},
}

@inproceedings{2719,
  abstract     = {Prediction of the evolutionary process is a long standing problem both in the theory of evolutionary biology and evolutionary computation (EC). It has long been realized that heritable variation is crucial to both the response to selection and the success of genetic algorithms. However, not all variation contributes in the same way to the response. Quantitative genetics has developed a large body of work trying to estimate and understand how different components of the variance in fitness in the population contribute to the response to selection. We illustrate how to apply some concepts of quantitative genetics to the analysis of genetic algorithms. In particular, we derive estimates for the short term prediction of the response to selection and we use variance decomposition to gain insight on local aspects of the landscape. Finally, we propose a new population based genetic algorithm that uses these methods to improve its operation.},
  author       = {Paixao, Tiago and Barton, Nicholas H},
  booktitle    = {Proceedings of the 15th annual conference on Genetic and evolutionary computation},
  location     = {Amsterdam, Netherlands},
  pages        = {845 -- 852},
  publisher    = {ACM},
  title        = {{A variance decomposition approach to the analysis of genetic algorithms}},
  doi          = {10.1145/2463372.2463470},
  year         = {2013},
}

@article{2720,
  abstract     = {Knowledge of the rate and fitness effects of mutations is essential for understanding the process of evolution. Mutations are inherently difficult to study because they are rare and are frequently eliminated by natural selection. In the ciliate Tetrahymena thermophila, mutations can accumulate in the germline genome without being exposed to selection. We have conducted a mutation accumulation (MA) experiment in this species. Assuming that all mutations are deleterious and have the same effect, we estimate that the deleterious mutation rate per haploid germline genome per generation is U = 0.0047 (95% credible interval: 0.0015, 0.0125), and that germline mutations decrease fitness by s = 11% when expressed in a homozygous state (95% CI: 4.4%, 27%). We also estimate that deleterious mutations are partially recessive on average (h = 0.26; 95% CI: –0.022, 0.62) and that the rate of lethal mutations is <10% of the deleterious mutation rate. Comparisons between the observed evolutionary responses in the germline and somatic genomes and the results from individual-based simulations of MA suggest that the two genomes have similar mutational parameters. These are the first estimates of the deleterious mutation rate and fitness effects from the eukaryotic supergroup Chromalveolata and are within the range of those of other eukaryotes.},
  author       = {Long, Hongan and Paixao, Tiago and Azevedo, Ricardo and Zufall, Rebecca},
  journal      = {Genetics},
  number       = {2},
  pages        = {527--540},
  publisher    = {Genetics Society of America},
  title        = {{Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila}},
  doi          = {10.1534/genetics.113.153536},
  volume       = {195},
  year         = {2013},
}

@article{2853,
  abstract     = {High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared with its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low, because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation.},
  author       = {Refardt, Dominik and Bergmiller, Tobias and Kümmerli, Rolf},
  issn         = {1471-2954},
  journal      = {Proceedings of the Royal Society of London Series B Biological Sciences},
  number       = {1759},
  publisher    = {The Royal Society},
  title        = {{Altruism can evolve when relatedness is low: Evidence from bacteria committing suicide upon phage infection}},
  doi          = {10.1098/rspb.2012.3035},
  volume       = {280},
  year         = {2013},
}

@article{499,
  abstract     = {Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing "persisters." Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure.},
  author       = {Wakamoto, Yurichi and Dhar, Neraaj and Chait, Remy P and Schneider, Katrin and Signorino Gelo, François and Leibler, Stanislas and Mckinney, John},
  journal      = {Science},
  number       = {6115},
  pages        = {91 -- 95},
  publisher    = {American Association for the Advancement of Science},
  title        = {{Dynamic persistence of antibiotic-stressed mycobacteria}},
  doi          = {10.1126/science.1229858},
  volume       = {339},
  year         = {2013},
}

@misc{9751,
  abstract     = {High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared to its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation.},
  author       = {Refardt, Dominik and Bergmiller, Tobias and Kümmerli, Rolf},
  publisher    = {Dryad},
  title        = {{Data from: Altruism can evolve when relatedness is low: evidence from bacteria committing suicide upon phage infection}},
  doi          = {10.5061/dryad.b1q2n},
  year         = {2013},
}

@article{2943,
  abstract     = {We examine whether the Escherichia coli chromosome is folded into a self-adherent nucleoprotein complex, or alternately is a confined but otherwise unconstrained self-avoiding polymer. We address this through in vivo visualization, using an inducible GFP fusion to the nucleoid-associated protein Fis to non-specifically decorate the entire chromosome. For a range of different growth conditions, the chromosome is a compact structure that does not fill the volume of the cell, and which moves from the new pole to the cell centre. During rapid growth, chromosome segregation occurs well before cell division, with daughter chromosomes coupled by a thin inter-daughter filament before complete segregation, whereas during slow growth chromosomes stay adjacent until cell division occurs. Image correlation analysis indicates that sub-nucleoid structure is stable on a 1min timescale, comparable to the timescale for redistribution time measured for GFP-Fis after photobleaching. Optical deconvolution and writhe calculation analysis indicate that the nucleoid has a large-scale coiled organization rather than being an amorphous mass. Our observations are consistent with the chromosome having a self-adherent filament organization.},
  author       = {Hadizadeh Yazdi, Nastaran and Guet, Calin C and Johnson, Reid and Marko, John},
  journal      = {Molecular Microbiology},
  number       = {6},
  pages        = {1318 -- 1333},
  publisher    = {Wiley-Blackwell},
  title        = {{Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions}},
  doi          = {10.1111/mmi.12071},
  volume       = {86},
  year         = {2012},
}

@article{3130,
  abstract     = {Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability-that is, by how easily they can be functionally replaced, for example through increased expression of other genes.},
  author       = {Bergmiller, Tobias and Ackermann, Martin and Silander, Olin},
  journal      = {PLoS Genetics},
  number       = {6},
  publisher    = {Public Library of Science},
  title        = {{Patterns of evolutionary conservation of essential genes correlate with their compensability}},
  doi          = {10.1371/journal.pgen.1002803},
  volume       = {8},
  year         = {2012},
}

@inproceedings{3136,
  abstract     = {Continuous-time Markov chains (CTMC) with their rich theory and efficient simulation algorithms have been successfully used in modeling stochastic processes in diverse areas such as computer science, physics, and biology. However, systems that comprise non-instantaneous events cannot be accurately and efficiently modeled with CTMCs. In this paper we define delayed CTMCs, an extension of CTMCs that allows for the specification of a lower bound on the time interval between an event's initiation and its completion, and we propose an algorithm for the computation of their behavior. Our algorithm effectively decomposes the computation into two stages: a pure CTMC governs event initiations while a deterministic process guarantees lower bounds on event completion times. Furthermore, from the nature of delayed CTMCs, we obtain a parallelized version of our algorithm. We use our formalism to model genetic regulatory circuits (biological systems where delayed events are common) and report on the results of our numerical algorithm as run on a cluster. We compare performance and accuracy of our results with results obtained by using pure CTMCs. © 2012 Springer-Verlag.},
  author       = {Guet, Calin C and Gupta, Ashutosh and Henzinger, Thomas A and Mateescu, Maria and Sezgin, Ali},
  location     = {Berkeley, CA, USA},
  pages        = {294 -- 309},
  publisher    = {Springer},
  title        = {{Delayed continuous time Markov chains for genetic regulatory circuits}},
  doi          = {10.1007/978-3-642-31424-7_24},
  volume       = {7358 },
  year         = {2012},
}