arXiv subjects

Kim Sneppen

Publications and source records attributed to Kim Sneppen.

At least 37 records · Page 2Linked to original sources

arXiv2012

Quality Control System Response to Stochastic Growth of Amyloid Fibrils

We introduce a stochastic model describing aggregation of misfolded proteins and degradation by the protein quality control system in a single cell. In analogy with existing literature, aggregates can grow, nucleate and fragment stochastically. We assume that the quality control system acts as an enzyme that can degrade aggregates at different stages of the growth process, with an efficiency that decreases with the size of the aggregate. We show how this stochastic dynamics, depending on the parameter choice, leads to two qualitatively different behaviors: a homeostatic state, where the quality control system is stable and aggregates of large sizes are not formed, and an oscillatory state, where the quality control system periodically breaks down, allowing for the formation of large aggregates. We discuss how these periodic breakdowns may constitute a mechanism for the sporadic development of neurodegenerative diseases.

q-bio.CB↗

arXiv2012

Clonal selection prevents tragedy of the commons when neighbors compete in a rock-paper-scissors game

The rock-paper-scissors game is a model example of the on-going cyclic turnover typical of many ecosystems, ranging from the terrestrial and aquatic to the microbial. Here we explore the evolution of a rock-paper-scissors system where three species compete for space. The species are allowed to mutate and change the speed by which they invade one another. In the case when all species have similar mutation rates, we observe a perpetual arms race where no single species prevails. When only two species mutate, their aggressions increase indefinitely until the ecosystem collapses and only the non-mutating species survives. Finally we show that when only one species mutates, group selection removes individual predators with the fastest growth rates, causing the growth rate of the species to stabilize. We explain this group selection quantitatively.

q-bio.PE↗

arXiv2012

Information spreading and development of cultural centers

The historical interplay between societies are governed by many factors, including in particular spreading of languages, religion and other symbolic traits. Cultural development, in turn, is coupled to emergence and maintenance of information spreading. Strong centralized cultures exist thanks to attention from their members, which faithfulness in turn relies on supply of information. Here, we discuss a culture evolution model on a planar geometry that takes into account aspects of the feedback between information spreading and its maintenance. Features of model are highlighted by comparing it to cultural spreading in ancient and medieval Europe, where it in particular suggests that long lived centers should be located in geographically remote regions.

physics.soc-ph↗

arXiv2011

Ecosystems with mutually exclusive interactions self-organize to a state of high diversity

Ecological systems comprise an astonishing diversity of species that cooperate or compete with each other forming complex mutual dependencies. The minimum requirements to maintain a large species diversity on long time scales are in general unknown. Using lichen communities as an example, we propose a model for the evolution of mutually excluding organisms that compete for space. We suggest that chain-like or cyclic invasions involving three or more species open for creation of spatially separated sub-populations that subsequently can lead to increased diversity. In contrast to its non-spatial counterpart, our model predicts robust co-existence of a large number of species, in accordance with observations on lichen growth. It is demonstrated that large species diversity can be obtained on evolutionary timescales, provided that interactions between species have spatial constraints. In particular, a phase transition to a sustainable state of high diversity is identified.

q-bio.PE↗

arXiv2011

Locally self-organized quasi-critical percolation in a multiple disease model

Diseases emerge, persist and vanish in an ongoing battle for available hosts. Hosts, on the other hand, defend themselves by developing immunity that limits the ability of pathogens to reinfect them. We here explore a multi-disease system with emphasis on mutual exclusion. We demonstrate that such a system develops towards a steady state, where the spread of individual diseases self-organizes to a state close to that of critical percolation, without any global control mechanism or separation of time scale. For a broad range of introduction rates of new diseases, the likelihood of transmitting diseases remains approximately constant.

nlin.AO↗

arXiv2011

Modelling the Spatial Dynamics of Culture Spreading in the Presence of Cultural Strongholds

Cultural competition has throughout our history shaped and reshaped the geography of boundaries between humans. Language and culture are intimately connected and linguists often use distinctive keywords to quantify the dynamics of information spreading in societies harbouring strong culture centres. One prominent example, which is addressed here, is Kyoto's historical impact on Japanese culture. We construct a first minimal model, based on shared properties of linguistic maps, to address the interplay between information flow and geography. In particular, we show that spreading of information over Japan in the pre-modern time can be described as a Eden growth process, with noise levels corresponding to coherent spatial patches of sizes given by a single days walk, and with patch-to-patch communication time comparable to the time between human generations.

physics.soc-ph↗

arXiv2010

Theory for stability and regulation of epigenetic landscapes

Cells can often choose among several stably heritable phenotypes. Examples are the expression of genes in eukaryotic cells where long chromosomal regions can adopt persistent and heritable silenced or active states, that may be associated with positive feedback in dynamic modification of nucleosomes. We generalize this mechanism in terms of bistability associated with valleys in an epigenetic landscape. A transfer matrix method was used to rigorously follow the system through the disruptive process of cell division. This combined treatment of noisy dynamics both between and during cell division provides an efficient way to calculate the stability of alternative states in a broad range of epigenetic systems.

q-bio.MN↗

arXiv2010

Toolbox model of evolution of prokaryotic metabolic networks and their regulation

It has been reported that the number of transcription factors encoded in prokaryotic genomes scales approximately quadratically with their total number of genes. We propose a conceptual explanation of this finding and illustrate it using a simple model in which metabolic and regulatory networks of prokaryotes are shaped by horizontal gene transfer of coregulated metabolic pathways. Adapting to a new environmental condition monitored by a new transcription factor (e.g., learning to use another nutrient) involves both acquiring new enzymes and reusing some of the enzymes already encoded in the genome. As the repertoire of enzymes of an organism (its toolbox) grows larger, it can reuse its enzyme tools more often and thus needs to get fewer new ones to master each new task. From this observation, it logically follows that the number of functional tasks and their regulators increases faster than linearly with the total number of genes encoding enzymes. Genomes can also shrink, e.g., because of a loss of a nutrient from the environment, followed by deletion of its regulator and all enzymes that become redundant. We propose several simple models of network evolution elaborating on this toolbox argument and reproducing the empirically observed quadratic scaling. The distribution of lengths of pathway branches in our model agrees with that of the real-life metabolic network of Escherichia coli. Thus, our model provides a qualitative explanation for broad distributions of regulon sizes in prokaryotes.

q-bio.MN↗

arXiv2010

Organizational structure and communication networks in a university environment

The ``six degrees of separation" between any two individuals on Earth has become emblematic of the 'small world' theme, even though the information conveyed via a chain of human encounters decays very rapidly with increasing chain length, and diffusion of information via this process may be very inefficient in large human organizations. The information flow on a communication network in a large organization, the University of Oslo, has been studied by analyzing e-mail records. The records allow for quantification of communication intensity across organizational levels and between organizational units (referred to as ``modules"). We find that the number of e-mails messages within modules scales with module size to the power of $1.29\pm .06$, and the frequency of communication between individuals decays exponentially with the number of links required upwards in the organizational hierarchy before they are connected. Our data also indicates that the number of messages sent by administrative units is proportional to the number of individuals at lower levels in the administrative hierarchy, and the ``divergence of information" within modules is associated with this linear relationship. The observed scaling is consistent with a hierarchical system in which individuals far apart in the organization interact little with each other and receive a disproportionate number of messages from higher levels in the administrative hierarchy.

physics.soc-ph↗

arXiv2010

Time walkers and spatial dynamics of ageing information

The distribution of information is essential for living system's ability to coordinate and adapt. Random walkers are often used to model this distribution process and, in doing so, one effectively assumes that information maintains its relevance over time. But the value of information in social and biological systems often decay and must continuously be updated. To capture the spatial dynamics of ageing information, we introduce time walkers. A time walker moves like a random walker, but interacts with traces left by other walkers, some representing older information, some newer. The traces forms a navigable information landscape. We quantify the dynamical properties of time walkers moving on a two-dimensional lattice and the quality of the information landscape generated by their movements. We visualise the self-similar landscape as a river network, and show that searching in this landscape is superior to random searching and scales as the length of loop-erased random walks.

cond-mat.stat-mech↗

arXiv2009

Modeling of the genetic switch of bacteriophage TP901-1: A heteromer of CI and MOR ensures robust bistability

The lytic-lysogenic switch of the temperate lactococcal phage TP901-1 is fundamentally different from that of phage lambda. In phage TP901-1, the lytic promoter PL is repressed by CI whereas repression of the lysogenic promoter PR requires the presence of both of the antagonistic regulator proteins, MOR and CI. We model the central part of the switch and compare the two cases for PR repression: the one where the two regulators interact only on the DNA, and the other where the two regulators form a heteromer complex in the cytoplasm prior to DNA binding. The models are analyzed for bistability, and the predicted promoter repression folds are compared to experimental data. We conclude that the experimental data are best reproduced the latter case, where a heteromer complex forms in solution. We further find that CI sequestration by the formation of MOR:CI complexes in cytoplasm makes the genetic switch robust.

q-bio.MN↗

arXiv2008

Efficient Degradation and Expression Prioritization with Small RNAs

We build a simple model for feedback systems involving small RNA (sRNA) molecules based on the iron metabolism system in the bacterium E. coli, and compare it with the corresponding system in H. pylori which uses purely transcriptional regulation. This reveals several unique features of sRNA based regulation that could be exploited by cells. Firstly, we show that sRNA regulation can maintain a smaller turnover of target mRNAs than transcriptional regulation, without sacrificing the speed of response to external shocks. Secondly, we propose that a single sRNA can prioritize the usage of different target mRNAs. This suggests that sRNA regulation would be more common in more complex systems which need to co-regulate many mRNAs efficiently.

q-bio.MN↗

arXiv2008

The Generation of Promoter-Mediated Transcriptional Noise in Bacteria

Noise in the expression of a gene produces fluctuations in the concentration of the gene product. These fluctuations can interfere with optimal function or can be exploited to generate beneficial diversity between cells; gene expression noise is therefore expected to be subject to evolutionary pressure. Shifts between modes of high and low rates of transcription initiation at a promoter appear to contribute to this noise both in eukaryotes and prokaryotes. However, models invoked for eukaryotic promoter noise such as stable activation scaffolds or persistent nucleosome alterations seem unlikely to apply to prokaryotic promoters. We consider the relative importance of the steps required for transcription initiation. The 3-step transcription initiation model of McClure is extended into a mathematical model that can be used to predict consequences of additional promoter properties. We show in principle that the transcriptional bursting observed at an E. coli promoter by Golding et al. (2005) can be explained by stimulation of initiation by the negative supercoiling behind a transcribing RNA polymerase (RNAP) or by the formation of moribund or dead-end RNAP-promoter complexes. Both mechanisms are tunable by the alteration of promoter kinetics and therefore allow the optimization of promoter mediated noise.

q-bio.MN↗

arXiv2008

Ribosome collisions and Translation efficiency: Optimization by codon usage and mRNA destabilization

Individual mRNAs are translated by multiple ribosomes that initiate translation with a few seconds interval. The ribosome speed is codon dependant, and ribosome queuing has been suggested to explain specific data for translation of some mRNAs in vivo. By modelling the stochastic translation process as a traffic problem, we here analyze conditions and consequences of collisions and queuing. The model allowed us to determine the on-rate (0.8 to 1.1 initiations per sec) and the time (1 sec) the preceding ribosome occludes initiation for Escherichia coli lacZ mRNA in vivo. We find that ribosome collisions and queues are inevitable consequences of a stochastic translation mechanism that reduce the translation efficiency substantially on natural mRNAs. The cells minimize collisions by having its mRNAs being unstable and by a highly selected codon usage in the start of the mRNA. The cost of mRNA breakdown is offset by the concomitant increase in translational efficiency.

q-bio.SC↗

arXiv2008

Dynamical Analysis on Gene Activity in the Presence of Repressors and an Interfering Promoter

Transcription is regulated through interplay between transcription factors, an RNA polymerase(RNAP), and a promoter. Even for a simple repressive transcription factor that disturbs promoter activity at the initial binding of RNAP, its repression level is not determined solely by the dissociation constant of transcription factor but is sensitive to the time scales of processes in RNAP. We first analyse the promoter activity under strong repression by a slow binding repressor, in which case transcriptions occur in a burst, followed by a long quiescent period while a repressor binds to the operator; the number of transcriptions, the bursting and the quiescent times are estimated by reaction rates. We then examine interference effect from an opposing promoter, using the correlation function of transcription initiations for a single promoter. The interference is shown to de-repress the promoter because RNAP's from the opposing promoter most likely encounter the repressor and remove it in case of strong repression. This de-repression mechanism should be especially prominent for the promoters that facilitate fast formation of open complex with the repressor whose binding rate is slower than about 1/sec. Finally, we discuss possibility of this mechanism for high activity of promoter PR in the hyp-mutant of lambda phage.

q-bio.MN↗

arXiv2008

Kolmogorov scaling from random force fields

We show that the classical Kolmogorov and Richardson scaling laws in fully developed turbulence are consistent with a random Gaussian force field. Numerical simulations of a shell model approximation to the Navier-Stokes equations suggest that the fluctuations in the force (acceleration) field are scale independent throughout the inertial regime. We conjecture that Lagrangian statistics of the relative velocity in a turbulent flow is determined by the typical force field, whereas the multiscaling is associated to extreme events in the force field fluctuations.

nlin.CD↗

arXiv2007

One Hub-One Process: A Tool Based View on Regulatory Network Topology

The relationship between the regulatory design and the functionality of molecular networks is a key issue in biology. Modules and motifs have been associated to various cellular processes, thereby providing anecdotal evidence for performance based localization on molecular networks. To quantify structure-function relationship we investigate similarities of proteins which are close in the regulatory network of the yeast Saccharomyces Cerevisiae. We find that the topology of the regulatory network show weak remnants of its history of network reorganizations, but strong features of co-regulated proteins associated to similar tasks. This suggests that local topological features of regulatory networks, including broad degree distributions, emerge as an implicit result of matching a number of needed processes to a finite toolbox of proteins.

q-bio.MN↗

arXiv2007

Cost and Capacity of Signaling in the Escherichia coli Protein Reaction Network

In systems biology new ways are required to analyze the large amount of existing data on regulation of cellular processes. Recent work can be roughly classified into either dynamical models of well-described subsystems, or coarse-grained descriptions of the topology of the molecular networks at the scale of the whole organism. In order to bridge these two disparate approaches one needs to develop simplified descriptions of dynamics and topological measures which address the propagation of signals in molecular networks. Here, we consider the directed network of protein regulation in E. coli, characterizing its modularity in terms of its potential to transmit signals. We demonstrate that the simplest measure based on identifying sub-networks of strong components, within which each node could send a signal to every other node, indeed partitions the network into functional modules. We then suggest measures to quantify the cost and spread associated with sending a signal between any particular pair of proteins. Thereby, we address the signalling specificity within and between modules, and show that in the regulation of E.coli there is a systematic reduction of the cost and spread for signals traveling over more than two intermediate reactions.

q-bio.MN↗