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Olivier Rivoire

Publications and source records attributed to Olivier Rivoire.

At least 19 recordsLinked to original sources

Learning to outgrow the competition: reaction-diffusion systems that adapt to time-dependent environments

A fundamental challenge in both biology and engineering is understanding how adaptation can emerge from simple physical or chemical building blocks. Biological adaptation appears to rely on two key capabilities: information processing, to enable learning of complex tasks, and reproduction, to give such learning its value through reproductive success. Creating and coordinating these capabilities poses both a formidable engineering challenge and a fundamental evolutionary puzzle. Here, we propose a model in which learning and reproduction emerge jointly from simple, nonequilibrium chemical systems, without prior design or evolution. The model's essential features are that it supports many steady states and spatial heterogeneities, upon which adaptation arises solely from exposure to time-varying influxes of reactants, without any predesigned program or memory. The adaptive response is specific to the temporal sequence of environmental changes, yet general enough to extend to related sequences. Learning manifests in several forms: it is reinforced through repeated exposure to the same environmental sequence, representing a form of self-learning, and enhanced through spatial interactions, corresponding to a form of collective learning. Moreover, an adapted state can accelerate adaptation in nearby regions, providing a mechanism akin to teacher-guided learning. By coupling environmental variations to stochastic reaction-diffusion dynamics, our model establishes a minimal physical framework in which learning of complex environments and selective amplification of the states that encode them, arise directly from nonequilibrium chemical processes.

cond-mat.stat-mech↗

Evolutionary features in a minimal physical system: diversity, selection, growth, inheritance, and adaptation

We present a simple physical model that recapitulates several features of biological evolution, while being based only on thermally-driven attachment and detachment of elementary building blocks. Through its dynamics, this model samples a large and diverse array of non-equilibrium steady states, both within and between independent trajectories. These dynamics exhibit directionality with a quantity that increases in time, selection and preferential spatial expansion of particular states, as well as inheritance in the form of correlated compositions between successive states, and environment-dependent adaptation. The model challenges common conceptions regarding the requirements for life-like properties: it does not involve separate mechanisms for metabolism, replication and compartmentalization, stores and transmits digital information without template replication or assembly of large molecules, exhibits selection both without and with reproduction, and undergoes growth without autocatalysis. As the model is based on generic physical principles, it is amenable to various experimental implementations.

q-bio.PE↗

One-way catalysis in a solvable lattice model

Catalysts speed up chemical reactions with no energy input and without being transformed in the process, therefore leaving equilibrium constants unchanged. Some catalysts, however, are much more efficient at accelerating one direction of a reaction. Is it possible for catalysis to be strictly unidirectional, accelerating only one direction of a reaction? Can we observe directional catalysis by analyzing the microscopic trajectory of a single reactant undergoing conversions between a substrate and a product state? We use the framework of a simple but exactly solvable lattice model to study these questions. The model provides examples of strictly one-way catalysts and illustrates a mathematical relationship between the asymmetric transition rates that underlie directional catalysis and the symmetric transition fluxes that underlie chemical equilibrium. The degree of directionality generally depends on the catalytic mechanism and we compare different mechanisms to show how they can obey different scaling laws.

cond-mat.soft↗

A Unified View of Allostery

Allostery is a fundamental property of proteins that represents the functional coupling between distantly located sites. In different manifestations, this property underlies signal transduction, gene expression, and regulation -- elementary reactions in networks comprising cellular information and metabolic processing systems. In this work, we present a reduced theoretical model for allostery that encompasses the many diverse mechanisms described in past work. What emerges is a basic classification of different forms of allostery into two groups: those that couple distant sites through soft normal modes within a single state, and those that possess multiple states, with effective interactions between sites emerging only upon transitioning between these states. This work serves to unify the extensive past theoretical work on the phenomenology and machinery of allostery in proteins.

q-bio.BM↗

Design principles, growth laws, and competition of minimal autocatalysts

The apparent difficulty of designing simple autocatalysts that grow exponentially in the absence of enzymes, external drives or ingenious internal mechanisms severely constrains scenarios for the emergence of evolution by natural selection in chemical and physical systems. Here, we systematically analyze these difficulties in the context of one of the simplest and most generic autocatalysts: a dimeric molecule that duplicates by templated ligation. We show that despite its simplicity, such an autocatalyst can achieve exponential growth autonomously. This only requires that the rate of the spontaneous dimerization, the interactions between molecules, and the concentrations of substrates and products are in appropriate ranges. We also show, however, that it is possible to design as simple sub-exponential autocatalysts that have an advantage over exponential autocatalysts when competing for a common resource. We reach these conclusions by developing a general theoretical framework based on kinetic barrier diagrams. Besides challenging commonly accepted assumptions in the field of the origin of life, our results provide a blueprint for the experimental realization of elementary autocatalysts exhibiting a form of natural selection, whether on a molecular or colloidal scale.

q-bio.BM↗

On Kinetic Constraints That Catalysis Imposes on Elementary Processes

Catalysis, the acceleration of product formation by a substance that is left unchanged, typically results from multiple elementary processes, including diffusion of the reactants toward the catalyst, chemical steps, and release of the products. While efforts to design catalysts are often focused on accelerating the chemical reaction on the catalyst, catalysis is a global property of the catalytic cycle that involves all processes. These are controlled by both intrinsic parameters such as the composition and shape of the catalyst and extrinsic parameters such as the concentration of the chemical species at play. We examine here the conditions that catalysis imposes on the different steps of a reaction cycle and the respective role of intrinsic and extrinsic parameters of the system on the emergence of catalysis by using an approach based on first-passage times. We illustrate this approach for various decompositions of a catalytic cycle into elementary steps, including non-Markovian decompositions, which are useful when the presence and nature of intermediate states are a priori unknown. Our examples cover different types of reactions and clarify the constraints on elementary steps and the impact of species concentrations on catalysis.

physics.chem-ph↗

On the exclusion of exponential autocatalysts by sub-exponential autocatalysts

Selection among autocatalytic species fundamentally depends on their growth law: exponential species, whose number of copies grows exponentially, are mutually exclusive, while sub-exponential ones, whose number of copies grows polynomially, can coexist. Here we consider competitions between autocatalytic species with different growth laws and make the simple yet counterintuitive observation that sub-exponential species can exclude exponential ones while the reverse is, in principle, impossible. This observation has implications for scenarios pertaining to the emergence of natural selection.

q-bio.PE↗

How flexibility can enhance catalysis

Conformational changes are observed in many enzymes, but their role in catalysis is highly controversial. Here we present a theoretical model that illustrates how rigid catalysts can be fundamentally limited and how a conformational change induced by substrate binding can overcome this limitation, ultimately enabling barrier-free catalysis. The model is deliberately minimal, but the principle it illustrates is general and consistent with unique features of proteins as well as with previous informal proposals to explain the superiority of enzymes over other classes of catalysts. Implementing the discriminative switch suggested by the model could help overcome limitations currently encountered in the design of artificial catalysts.

q-bio.BM↗

Cell behavior in the face of uncertainty

Organisms that grow and survive in uncertain environments may need to change their physiological state as the environment changes. When the environment is uncertain, one strategy known as bet-hedging is to make these changes randomly and independently of the environment, to ensure that at least part of the population is well adapted. Organisms that collect information from their environment may also use this information to modulate their changes of physiological states. We review these different strategies and point out parallels with the theory of optimal financial investments.

q-bio.CB↗

Catalysis from the bottom-up

Catalysis, the acceleration of chemical reactions by molecules that are not consumed in the process, is essential to living organisms but currently absent in physical systems that aspire to emulate biological functionalities with artificial components. Here we demonstrate how to design a catalyst using spherical building blocks interacting via programmable potentials, and show that a minimal catalyst design, a rigid dimer, can accelerate a ubiquitous elementary reaction, the cleaving of a bond. By combining coarse-grained molecular dynamics simulations and theory, and by comparing the mean reaction time in the presence and absence of the catalyst, we derive geometrical and physical constraints for its design and determine the reaction conditions under which catalysis emerges in the system. The framework and design rules that we introduce are general and can be applied to experimental systems on a wide range of scales, from micron size DNA-coated colloids to centimeter size magnetic handshake materials, opening the door to the realization of self-regulated artificial systems with bio-inspired functionalities.

cond-mat.soft↗

On the emergence of single versus multi-state allostery

Several physical mechanisms have been proposed to explain allostery in proteins. They differ by the number of internal states that they assume a protein to occupy, leaving open the question of what controls the emergence of these distinct physical forms of allostery. Here, we analyze a simplified model of protein allostery under a range of physical and evolutionary constraints. We find that two archetypal mechanisms can emerge through evolution: a single-state mechanism where ligand binding induces a displacement along a soft normal mode or a multi-state mechanism where ligand binding induces a switch across an energy barrier to a different stable state. Importantly, whenever the two mechanisms are possible, the multi-state mechanism confers a stronger allosteric effect and thus a selective advantage. This work defines the essential constraints on single or multi-state allostery, and sets the stage for a physical theory of its evolutionary origins.

q-bio.BM↗

Sex as information processing: optimality and evolution

The long-term growth rate of populations in varying environments quantifies the evolutionary value of processing the information that biological individuals inherit from their ancestors and acquire from their environment. Previous models were limited to asexual reproduction with inherited information coming from a single parent with no recombination. We present a general extension to sexual reproduction and an analytical solution for a particular but important case, the infinitesimal model of quantitative genetics which assumes traits to be normally distributed. We study with this model the conditions under which sexual reproduction is advantageous and can evolve in the context of autocorrelated or directionally varying environments, mutational biases, spatial heterogeneities and phenotypic plasticity. Our results generalize and unify previous analyses. We also examine the proposal made by Geodakyan that the presence of two phenotypically distinct sexes permits an optimal adaptation to varying environments. We verify that conditions exists where sexual dimorphism is adaptive but find that its evolutionary value does not generally compensate for the two-fold cost of males.

q-bio.PE↗

Geometry and flexibility of optimal catalysts in a minimal elastic network model

We have a general knowledge of the principles by which catalysts accelerate the rate of chemical reactions but no precise understanding of the geometrical and physical constraints to which their design is subject. To analyze these constraints, we introduce a minimal model of catalysis based on elastic networks where the implications of the geometry and flexibility of a catalyst can be studied systematically. The model demonstrates the relevance and limitations of the principle of transition-state stabilization: optimal catalysts are found to have a geometry complementary to the transition state but a degree of flexibility that non-trivially depends on the parameters of the reaction as well as on external parameters such as the concentrations of reactants and products. The results illustrate how simple physical models can provide valuable insights on the design of catalysts.

q-bio.BM↗

Parsimonious evolutionary scenario for the origin of allostery and coevolution patterns in proteins

Proteins display generic properties that are challenging to explain by direct selection, notably allostery, the capacity to be regulated through long-range effects, and evolvability, the capacity to adapt to new selective pressures. An evolutionary scenario is proposed where proteins acquire these two features indirectly as a by-product of their selection for a more fundamental property, exquisite discrimination, the capacity to bind discriminatively very similar ligands. Achieving this task is shown to typically require proteins to undergo a conformational change. We argue that physical and evolutionary constraints impel this change to be controlled by a group of sites extending from the binding site. Proteins can thus acquire a latent potential for allosteric regulation and evolutionary adaptation because of long-range effects that initially arise as evolutionary spandrels. This scenario accounts for the groups of conserved and coevolving residues observed in multiple sequence alignments. However, we propose that most pairs of coevolving and contacting residues inferred from such alignments have a different origin, related to thermal stability. A physical model is presented that illustrates this evolutionary scenario and its implications. The scenario can be implemented in experiments of protein evolution to directly test its predictions.

q-bio.BM↗

Universal and idiosyncratic characteristic lengths in bacterial genomes

In condensed matter physics, simplified descriptions are obtained by coarse-graining the features of a system at a certain characteristic length, defined as the typical length beyond which some properties are no longer correlated. From a physics standpoint, in vitro DNA has thus a characteristic length of 300 base pairs (bp), the Kuhn length of the molecule beyond which correlations in its orientations are typically lost. From a biology standpoint, in vivo DNA has a characteristic length of 1000 bp, the typical length of genes. Since bacteria live in very different physico-chemical conditions and since their genomes lack translational invariance, whether larger, universal characteristic lengths exist is a non-trivial question. Here, we examine this problem by leveraging the large number of fully sequenced genomes available in public databases. By analyzing GC content correlations and the evolutionary conservation of gene contexts (synteny) in hundreds of bacterial chromosomes, we conclude that a fundamental characteristic length around 10-20 kb can be defined. This characteristic length reflects elementary structures involved in the coordination of gene expression, which are present all along the genome of nearly all bacteria. Technically, reaching this conclusion required us to implement methods that are insensitive to the presence of large idiosyncratic genomic features, which may co-exist along these fundamental universal structures.

q-bio.GN↗

Transitions in optimal adaptive strategies for populations in fluctuating environments

Biological populations are subject to fluctuating environmental conditions. Different adaptive strategies can allow them to cope with these fluctuations: specialization to one particular environmental condition, adoption of a generalist phenotype that compromise between conditions, or population-wise diversification (bet-hedging). Which strategy provides the largest selective advantage in the long run depends on the range of accessible phenotypes and the statistics of the environmental fluctuations. Here, we analyze this problem in a simple mathematical model of population growth. First, we review and extend a graphical method to identify the nature of the optimal strategy when the environmental fluctuations are uncorrelated. Temporal correlations in environmental fluctuations open up new strategies that rely on memory but are mathematically challenging to study: we present here new analytical results to address this challenge. We illustrate our general approach by analyzing optimal adaptive strategies in the presence of trade-offs that constrain the range of accessible phenotypes. Our results extend several previous studies and have applications to a variety of biological phenomena, from antibiotic resistance in bacteria to immune responses in vertebrates.

q-bio.PE↗

Diversity of immune strategies explained by adaptation to pathogen statistics

Biological organisms have evolved a wide range of immune mechanisms to defend themselves against pathogens. Beyond molecular details, these mechanisms differ in how protection is acquired, processed and passed on to subsequent generations -- differences that may be essential to long-term survival. Here, we introduce a mathematical framework to compare the long-term adaptation of populations as a function of the pathogen dynamics that they experience and of the immune strategy that they adopt. We find that the two key determinants of an optimal immune strategy are the frequency and the characteristic timescale of the pathogens. Depending on these two parameters, our framework identifies distinct modes of immunity, including adaptive, innate, bet-hedging and CRISPR-like immunities, which recapitulate the diversity of natural immune systems.

q-bio.PE↗

Hierarchy and extremes in selections from pools of randomized proteins

Variation and selection are the core principles of Darwinian evolution, yet quantitatively relating the diversity of a population to its capacity to respond to selection is challenging. Here, we examine this problem at a molecular level in the context of populations of partially randomized proteins selected for binding to well-defined targets. We built several minimal protein libraries, screened them in vitro by phage display and analyzed their response to selection by high-throughput sequencing. A statistical analysis of the results reveals two main findings: first, libraries with same sequence diversity but built around different "frameworks" typically have vastly different responses, second, the distribution of responses within a library follows a simple scaling law. We show how an elementary probabilistic model based on extreme value theory rationalizes these findings. Our results have implications for designing synthetic protein libraries, for estimating the density of functional biomolecules in sequence space, for characterizing diversity in natural populations and for experimentally investigating the concept of evolvability, or potential for future evolution.

q-bio.PE↗