arXiv subjects

Kunihiko Kaneko

Publications and source records attributed to Kunihiko Kaneko.

At least 91 records · Page 5Linked to original sources

arXiv2015

Pluripotency, differentiation, and reprogramming: A gene expression dynamics model with epigenetic feedback regulation

Characterization of pluripotent states, in which cells can both self-renew and differentiate, and the irreversible loss of pluripotency are important research areas in developmental biology. In particular, an understanding of these processes is essential to the reprogramming of cells for biomedical applications, i.e., the experimental recovery of pluripotency in differentiated cells. Based on recent advances in dynamical-systems theory for gene expression, we propose a gene-regulatory-network model consisting of several pluripotent and differentiation genes. Our results show that cellular-state transition to differentiated cell types occurs as the number of cells increases, beginning with the pluripotent state and oscillatory expression of pluripotent genes. Cell-cell signaling mediates the differentiation process with robustness to noise, while epigenetic modifications affecting gene expression dynamics fix the cellular state. These modifications ensure the cellular state to be protected against external perturbation, but they also work as an epigenetic barrier to recovery of pluripotency. We show that overexpression of several genes leads to the reprogramming of cells, consistent with the methods for establishing induced pluripotent stem cells. Our model, which involves the inter-relationship between gene expression dynamics and epigenetic modifications, improves our basic understanding of cell differentiation and reprogramming.

q-bio.MN↗

arXiv2015

Inverse Relationship Between Molecular Diversity And Resource Abundances

Cell reproduction involves replication of diverse molecule species, in contrast to simple replication system with fewer components. Here, we address why such diversity is sustained despite the efficiency of simple replication systems, using a cell model with catalytic reaction dynamics that grew by uptake of environmental resources. Limited resources led to increased diversity of components within the system, and the number of coexisting species increased with a negative power of the resource abundances. The diversity was explained from the optimum growth speed of the cell, determined by a tradeoff between the utility of diverse resources and the concentration onto fewer components to increase the reaction rate.

q-bio.CB↗

arXiv2015

Evolution-Development Congruence in Pattern Formation Dynamics: Bifurcations in Gene Expressions and Regulation of Networks Structures

Search for possible relationships between phylogeny and ontogeny is one of the most important issues in the field of evolutionary developmental biology. By representing developmental dynamics of spatially located cells with gene expression dynamics with cell-to-cell interaction under external morphogen gradient, evolved are gene regulation networks under mutation and selection with the fitness to approach a prescribed spatial pattern of expressed genes. For most of thousands of numerical evolution experiments, evolution of pattern over generations and development of pattern by an evolved network exhibit remarkable congruence. Here, both the pattern dynamics consist of several epochs to form successive stripe formations between quasi-stationary regimes. In evolution, the regimes are generations needed to hit relevant mutations, while in development, they are due to the emergence of slowly varying expression that controls the pattern change. Successive pattern changes are thus generated, which are regulated by successive combinations of feedback or feedforward regulations under the upstream feedforward network that reads the morphogen gradient. By using a pattern generated by the upstream feedforward network as a boundary condition, downstream networks form later stripe patterns. These epochal changes in development and evolution are represented as same bifurcations in dynamical-systems theory, and this agreement of bifurcations lead to the evolution-development congruences. Violation of the evolution-development congruence, observed exceptionally, is shown to be originated in alteration of the boundary due to mutation at the upstream feedforward network. Our results provide a new look on developmental stages, punctuated equilibrium, developmental bottlenecks, and evolutionary acquisition of novelty in morphogenesis.

q-bio.PE↗

arXiv2015

Theoretical Analysis of Discreteness-Induced Transition in Autocatalytic Reaction Dynamics

Transitions in the qualitative behavior of chemical reaction dynamics with a decrease in molecule number have attracted much attention. Here, a method based on a Markov process with a tridiagonal transition matrix is applied to the analysis of this transition in reaction dynamics. The transition to bistability due to the small-number effect and the mean switching time between the bistable states are analytically calculated in agreement with numerical simulations. In addition, a novel transition involving the reversal of the chemical reaction flow is found in the model under an external flow, and also in a three-component model. The generality of this transition and its correspondence to biological phenomena are also discussed.

q-bio.MN↗

arXiv2015

Global Relationships in Fluctuation and Response in Adaptive Evolution

Cells generally change their internal state to adapt to an environmental change, and accordingly evolve in response to the new conditions. This process involves phenotypic changes that occur over several different time scales, ranging from faster environmental adaptation without a corresponding change in the genomic sequence to slower evolutionary dynamics involving genetic mutations and subsequent selection. In this regard, a question arises as to whether there are any relationships between such phenotypic changes over the different time scales at which adaptive evolution occurs. In this study, we analyzed simulated adaptive evolution in a simple cell model, and found that proportionality between concentration changes in adaptation and evolution over all components, and the proportion coefficients were closely linked to the change in the growth rate of a cell. Furthermore, we demonstrated that the phenotypic variances in component concentrations due to (non-genetic) noise and genomic alternations are proportional across all components. These global relationships in cellular states were also supported by phenomenological theory and transcriptome analysis of laboratory evolution in {\it Escherichia coli}. These findings provide a basis for the development of a quantitative theory of plasticity and robustness, and to determine the general restriction of phenotypic changes imposed by evolution.

q-bio.PE↗

arXiv2014

Transition to diversification by competition for resources in catalytic reaction networks

All life, including cells and artificial protocells, must integrate diverse molecules into a single unit in order to reproduce. Despite expected pressure to evolve a simple system with the fastest replication speed, the mechanism by which the use of the great variety of components, and the coexistence of diverse cell-types with different compositions are achieved is as yet unknown. Here we show that coexistence of such diverse compositions and cell-types is the result of competitions for a variety of limited resources. We find that a transition to diversity occurs both in chemical compositions and in protocell types, as the resource supply is decreased, when the maximum inflow and consumption of resources are balanced.

q-bio.CB↗

arXiv2014

Universal relationship in gene-expression changes for cells in steady-growth state

Cells adapt to different conditions by altering a vast number of components, which is measurable using transcriptome analysis. Given that a cell undergoing steady growth is constrained to sustain each of its internal components, the abundance of all the components in the cell has to be roughly doubled during each cell division event. From this steady-growth constraint, expression of all genes is shown to change along a one-parameter curve in the state space in response to the environmental stress. This leads to a global relationship that governs the cellular state: By considering a relatively moderate change around a steady state, logarithmic changes in expression are shown to be proportional across all genes, upon alteration of stress strength, with the proportionality coefficient given by the change in the growth rate of the cell. This theory is confirmed by transcriptome analysis of Escherichia Coli in response to several stresses.

q-bio.CB↗

arXiv2014

Entropy production of a steady-growth cell with catalytic reactions

Cells generally convert external nutrient resources to support metabolismand growth. Understanding the thermodynamic efficiency of this conversion is essential to determine the general characteristics of cellular growth. Using a simple protocell model with catalytic reaction dynamics to synthesize the necessary enzyme and membrane components from nutrients, the entropy production per unit cell-volume growth is calculated analytically and numerically based on the rate equation for chemical kinetics and linear non-equilibrium thermodynamics. The minimal entropy production per unit cell growth is found to be achieved at a non-zero nutrient uptake rate, rather than at a quasi-static limit as in the standard Carnot engine. This difference appears because the equilibration mediated by the enzyme exists only within cells that grow through enzyme and membrane synthesis. Optimal nutrient uptake is also confirmed by protocell models with many chemical components synthesized through a catalytic reaction network. The possible relevance of the identified optimal uptake to optimal yield for cellular growth is also discussed.

q-bio.SC↗

arXiv2013

The Baldwin effect under multi-peaked fitness landscapes: Phenotypic fluctuation accelerates evolutionary rate

Phenotypic fluctuations and plasticity can generally affect the course of evolution, a process known as the Baldwin effect. Several studies have recast this effect and claimed that phenotypic plasticity acceler- ates evolutionary rate (the Baldwin expediting effect); however, the validity of this claim is still controversial. In this study, we investi- gate the evolutionary population dynamics of a quantitative genetic model under a multi-peaked fitness landscape, in order to evaluate the validity of the effect. We provide analytical expressions for the evolutionary rate and average population fitness. Our results indicate that under a multi-peaked fitness landscape, phenotypic fluctuation always accelerates evolutionary rate, but it decreases the average fit- ness. As an extreme case of the trade-off between the rate of evolution and average fitness, phenotypic fluctuation is shown to accelerate the error catastrophe, in which a population fails to sustain a high-fitness peak. In the context of our findings, we discuss the role of phenotypic plasticity in adaptive evolution.

q-bio.PE↗

arXiv2013

Evolution of Robustness and Plasticity under Environmental Fluctuation: Formulation in terms of Phenotypic Variances

The characterization of plasticity, robustness, and evolvability, an important issue in biology, is studied in terms of phenotypic fluctuations. By numerically evolving gene regulatory networks, the proportionality between the phenotypic variances of epigenetic and genetic origins is confirmed. The former is given by the variance of the phenotypic fluctuation due to noise in the developmental process; and the latter, by the variance of the phenotypic fluctuation due to genetic mutation. The relationship suggests a link between robustness to noise and to mutation, since robustness can be defined by the sharpness of the distribution of the phenotype. Next, the proportionality between the variances is demonstrated to also hold over expressions of different genes (phenotypic traits) when the system acquires robustness through the evolution. Then, evolution under environmental variation is numerically investigated and it is found that both the adaptability to a novel environment and the robustness are made compatible when a certain degree of phenotypic fluctuations exists due to noise. The highest adaptability is achieved at a certain noise level at which the gene expression dynamics are near the critical state to lose the robustness. Based on our results, we revisit Waddington's canalization and genetic assimilation with regard to the two types of phenotypic fluctuations.

q-bio.PE↗

arXiv2013

Slow Stochastic Switching by Collective Chaos of Fast Elements

Coupled dynamical systems with one slow element and many fast elements are analyzed. By averaging over the dynamics of the fast variables, the adiabatic kinetic branch is introduced for the dynamics of the slow variable in the adiabatic limit. The dynamics without the limit are found to be represented by stochastic switching over these branches mediated by the collective chaos of the fast elements, while the switching frequency shows a complicated dependence on the ratio of the two timescales with some resonance structure. The ubiquity of the phenomena in the slow--fast dynamics is also discussed.

nlin.CD↗

arXiv2013

Minimal Model for Stem-Cell Differentiation

To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein expression networks consisting of two genes under cell--cell interactions mediated by the diffusion of a protein. Networks that show cell differentiation are extracted and two forms of symmetric differentiation based on Turing's mechanism and asymmetric differentiation are identified. In the latter network, the intracellular protein levels show oscillatory dynamics at a single-cell level, while cell-to-cell synchronicity of the oscillation is lost with an increase in the number of cells. Differentiation to a fixed-point type behavior follows with a further increase in the number of cells. The cell type with oscillatory dynamics corresponds to a stem cell that can both proliferate and differentiate, while the latter fixed-point type only proliferates. This differentiation is analyzed as a saddle-node bifurcation on an invariant circle, while the number ratio of each cell type is shown to be robust against perturbations due to self-consistent determination of the effective bifurcation parameter as a result of the cell--cell interaction. Complex cell differentiation is designed by combing these simple two-gene networks. The generality of the present differentiation mechanism, as well as its biological relevance, is discussed.

q-bio.CB↗

arXiv2013

Evolution of Genetic Redundancy : The Relevance of Complexity in Genotype-Phenotype Mapping

Genetic redundancy is ubiquitous and can be found in any organism. However, it has been argued that genetic redundancy reduces total population fitness, and therefore, redundancy is unlikely to evolve. In this letter, we study an evolutionary model with high-dimensional genotype-phenotype mapping (GPM) to investigate the relevance of complexity in GPM to the evolution of genetic redundancy. By applying the replica method to deal with quenched randomness, the redundancy dependence of the fitness is analytically obtained, which demonstrates that genetic redundancy can indeed evolve, provided that the GPM is complex. Our result provides a novel insight into how genetic redundancy evolves.

q-bio.PE↗

arXiv2012

Identifying dynamical systems with bifurcations from noisy partial observation

Dynamical systems are used to model a variety of phenomena in which the bifurcation structure is a fundamental characteristic. Here we propose a statistical machine-learning approach to derive lowdimensional models that automatically integrate information in noisy time-series data from partial observations. The method is tested using artificial data generated from two cell-cycle control system models that exhibit different bifurcations, and the learned systems are shown to robustly inherit the bifurcation structure.

q-bio.QM↗

arXiv2011

Generic temperature compensation of biological clocks by autonomous regulation of catalyst concentration

Circadian clocks ubiquitous in life forms ranging bacteria to multi-cellular organisms, often exhibit intrinsic temperature compensation; the period of circadian oscillators is maintained constant over a range of physiological temperatures, despite the expected Arrhenius form for the reaction coefficient. Observations have shown that the amplitude of the oscillation depends on the temperature but the period does not---this suggests that although not every reaction step is temperature independent, the total system comprising several reactions still exhibits compensation. We present a general mechanism for such temperature compensation. Consider a system with multiple activation energy barriers for reactions, with a common enzyme shared across several reaction steps with a higher activation energy. These reaction steps rate-limit the cycle if the temperature is not high. If the total abundance of the enzyme is limited, the amount of free enzyme available to catalyze a specific reaction decreases as more substrates bind to common enzyme. We show that this change in free enzyme abundance compensate for the Arrhenius-type temperature dependence of the reaction coefficient. Taking the example of circadian clocks with cyanobacterial proteins KaiABC consisting of several phosphorylation sites, we show that this temperature compensation mechanisms is indeed valid. Specifically, if the activation energy for phosphorylation is larger than that for dephosphorylation, competition for KaiA shared among the phosphorylation reactions leads to temperature compensation. Moreover, taking a simpler model, we demonstrate the generality of the proposed compensation mechanism, suggesting relevance not only to circadian clocks but to other (bio)chemical oscillators as well.

q-bio.MN↗

arXiv2011

Replica symmetry breaking in an adiabatic spin-glass model of adaptive evolution

We study evolutionary canalization using a spin-glass model with replica theory, where spins and their interactions are dynamic variables whose configurations correspond to phenotypes and genotypes, respectively. The spins are updated under temperature T_S, and the genotypes evolve under temperature T_J, according to the evolutionary fitness. It is found that adaptation occurs at T_S < T_S^{RS}, and a replica symmetric phase emerges at T_S^{RSB} < T_S < T_S^{RS}. The replica symmetric phase implies canalization, and replica symmetry breaking at lower temperatures indicates loss of robustness.

cond-mat.dis-nn↗

arXiv2011

Growth states of catalytic reaction networks exhibiting energy metabolism

All cells derive nutrition by absorbing some chemical and energy resources from the environment; these resources are used by the cells to reproduce the chemicals within them, which in turn leads to an increase in their volume. In this study, we introduce a protocell model exhibiting catalytic reaction dynamics, energy metabolism, and cell growth. Results of extensive simulations of this model show the existence of four phases with regard to the rates of both the influx of resources and the cell growth. These phases include an active phase with high influx and high growth rates, an inefficient phase with high influx but low growth rates, a quasi-static phase with low influx and low growth rates, and a death phase with negative growth rate. A mean field model well explains the transition among these phases as bifurcations. The statistical distribution of the active phase is characterized by a power law and that of the inefficient phase is characterized by a nearly equilibrium distribution. We also discuss the relevance of the results of this study to distinct states in the existing cells.

q-bio.CB↗

arXiv2011

Weber's Law in Autocatalytic Reaction Networks

Biological responses often obey Weber's law, according to which the magnitude of the response depends only on the fold change in the external input. In this study, we demonstrate that a system involving a simple autocatalytic reaction shows such response when a chemical is slowly synthesized by the reaction from a faster influx process. We also show that an autocatalytic reaction process occurring in series or in parallel can obey Weber's law with an oscillatory adaptive response. Considering the simplicity and ubiquity of the autocatalytic process, our proposed mechanism is thought to be commonly observed in biological reactions.

physics.bio-ph↗