Biology subjects

Rajon, E.

Publications and source records attributed to Rajon, E..

6 recordsLinked to original sources

bioRxiv2024

Thermodynamic consistency of autocatalytic cycles

Autocatalysis is seen as a potential key player in the origin of life, and perhaps more generally in the emergence of Darwinian dynamics. Building on recent formalizations of this phenomenon, we tackle the computational challenge of exhaustively detecting minimal autocatalytic cycles (autocatalytic cores) in reaction networks, and further evaluate the impact of thermodynamic constraints on their realization under mass action kinetics. We first characterize the complexity of the detection problem by proving its NP-completeness. This justifies the use of constraint solvers to list all cores in a given reaction network, and also to group them into compatible sets, composed of cores whose stoichiometric requirements are not contradictory. Crucially, we show that the introduction of thermodynamic realism does constrain the composition of these sets. Compatibility relationships among autocatalytic cores can indeed be disrupted when the reaction kinetics obey thermodynamic consistency throughout the network. On the contrary, these constraints have no impact on the realizability of isolated cores, unless upper or lower bounds are imposed on the concentrations of the reactants. Overall, by better characterizing the conditions of autocatalysis in complex reaction systems, this work brings us a step closer to assessing the contribution of this collective chemical behavior to the emergence of natural selection in the primordial soup. Significance StatementDescribing the processes behind the origin of life requires us to better understand selfamplifying dynamics in complex chemical systems. Detecting autocatalytic cycles is a critical but challenging step in this endeavor. After characterizing the computational complexity of this problem, we investigate the impact of thermodynamic realism on autocatalysis. We demonstrate that individual cycles, regardless of thermodynamic parameters, can always be activated as long as entities may occur at any required concentration. In contrast, two cycles can become mutually incompatible due to thermodynamic constraints, and will thus never run simultaneously. These results clarify the implications of physical realism for the realization of autocatalysis.

evolutionary biology↗

bioRxiv2022

(Epi)mutation rates and the evolution of composite trait architectures

Mutation rates vary widely along genomes and across inheritance systems. This suggests that complex traits - resulting from the contributions of multiple determinants - might be composite in terms of the underlying mutation rates. Here we investigate through mathematical modeling whether such an heterogeneity may drive changes in a traits architecture, especially in fluctuating environments where phenotypic instability can be beneficial. We first identify a convexity principle, related to the shape of the traits fitness function, setting conditions under which composite architectures should be adaptive or, conversely and more commonly, should be selected against. Simulations reveal, however, that applying this principle to realistic evolving populations requires taking into account pervasive epistatic interactions that take place in the system. Indeed, the fate of a mutation affecting the architecture depends on the (epi)genetic background, itself depending upon the current architecture in the population. We tackle this problem by borrowing the adaptive dynamics framework from evolutionary ecology - where it is routinely used to deal with such resident/mutant dependencies - and find that the principle excluding composite architectures generally prevails. Yet, the predicted evolutionary trajectories will typically depend on the initial architecture, possibly resulting in historical contingencies. Finally, by relaxing the large population size assumption, we unexpectedly find that not only the strength of selection on a traits architecture, but also its direction, depend on population size, revealing a new occurrence of the recently coined phenomenon of sign inversion.

evolutionary biology↗

bioRxiv2021

Proteome allocation and the evolution of metabolic cross-feeding

Metabolic cross-feeding (MCF) is a widespread type of ecological interaction where organisms share nutrients. In a common instance of MCF, an organism incompletely metabolises sugars and releases metabolites that are used by another as a carbon source to produce energy. Why would the former waste edible food, and why does this preferentially occur at specific locations in the sugar metabolic pathway (acetate and glycerol are preferentially exchanged) have challenged evolutionary theory for decades. Addressing these questions requires to model the cellular features involved; to this end, we built an explicit model of metabolic reactions, including their enzyme-driven catalysis and the cellular constraints acting on the proteome that may incur a cost to expressing all enzymes along a pathway. After showing that cells should in principle prioritise upstream reactions when metabolites are restrained inside the cell, we investigate how the diffusivity of these metabolites may trigger the emergence of MCF in a population. We find that the occurrence of MCF is rare and requires that an intermediate metabolite be extremely diffusive: indeed, up to high membrane permeability coefficients, the expected evolutionary outcome is not a diversification that resembles MCF but a single genotype that instead overexpresses downstream enzymes. Only at very high levels of membrane permeability and under distinctive sets of parameters should the population diversify and MCF evolve. These results help understand the origins of simple microbial communities, and may later be extended to investigate how evolution has progressively built up todays extremely diverse communities. Significance statementCan two species thrive on a single energetic resource? While the competitive exclusion principle predicts that one in the pair should go extinct, it may occur that an organism releases partly metabolised molecules in the environment, securing an ecological niche for a second organism in a specialisation process called metabolic cross-feeding. Here we investigate how evolution may favor the waste of a useful resource using a model that considers how a cell packed with proteins may be less efficient, hence favoring a shortening of metabolic pathways in order to reduce cell packing. Our model indicates that such specialisation only occurs under restricted conditions. Incidentally, this makes the signatures of cross-feeding, such as which metabolites are preferentially involved, quite predictable.

evolutionary biology↗

bioRxiv2020

Resource uptake and the evolution of moderately efficient enzymes

Enzymes speed up reactions that would otherwise be too slow to sustain the metabolism of self-replicators. Yet, most enzymes seem only moderately efficient, exhibiting kinetic parameters orders of magnitude lower than their expected physically achievable maxima and spanning over surprisingly large ranges of values. Here, we question how these parameters evolve using a mechanistic model where enzyme efficiency is a key component of individual competition for resources. We show that kinetic parameters are under strong directional selection only up to a point, above which enzymes appear to evolve under near-neutrality, thereby confirming the qualitative observation of other modeling approaches. While the existence of a large fitness plateau could potentially explain the extensive variation in enzyme features reported, we show using a population genetics model that such a widespread distribution is an unlikely outcome of evolution on a common landscape, as mutation-selection-drift balance occupy a narrow area even when very moderate biases towards lower efficiency are considered. Instead, differences in the evolutionary context encountered by each enzyme should be involved, such that each evolves on an individual, unique landscape. Our results point to drift and effective population size playing an important role, along with the kinetics of nutrient transporters, the tolerance to high concentrations of intermediate metabolites, and the reversibility of reactions. Enzyme concentration also shapes selection on kinetic parameters, but we show that the joint evolution of concentration and efficiency does not yield extensive variance in evolutionary outcomes when documented costs to protein expression are applied.

evolutionary biology↗

bioRxiv2018

(In)exhaustible suppliers for evolution? Epistatic selection tunes the adaptive potential of non-genetic inheritance

Non-genetic inheritance media, from methyl-accepting cytosines to culture, tend to mutate more frequently than DNA sequences. Whether or not this makes them inexhaustible suppliers for adaptive evolution will depend on the effect of non-genetic mutations (hereafter epimutations) on fitness-related traits. Here we investigate how the magnitude of these effects might themselves evolve. More specifically, we examine the hypothesis that natural selection could set boundaries to the adaptive potential of non-genetic inheritance media due to their higher mutability. In our model, the genetic and epigenetic contributions to a non-neutral phenotype are controlled by an epistatic modifier locus, which we let evolve under the combined effects of drift and selection, in stable and in variable environments. We show that a pure genetic control evolves when the environment is stable, provided that the population is large enough, such that the phenotype becomes robust to frequent epimutations. When the environment fluctuates, however, the direction of selection on the modifier locus also fluctuates and can overall produce a large non-genetic contribution to the phenotype, especially when the epimutation rate matches the rate of environmental variation. We further show that selection on the modifier locus is mostly direct - i.e. it does not rely on subsequent effects in future generations - as our results are generally insensitive to recombination. These results suggest that unstable inheritance media might significantly contribute to fitness variation of traits subject to highly variable selective pressures, but little to traits responding to scarcely variable aspects of the environment, which likely represent a majority. More generally, our study demonstrates that the rate of mutation and the adaptive potential of any inheritance media should not be seen as independent properties.

evolutionary biology↗

bioRxiv2017

How evolution draws trade-offs

Recent empirical evidence suggest that trade-off shapes can evolve, challenging the classical image of their high entrenchment. Here we model the evolution of the physiological mechanism that controls the allocation of a resource to two traits, by mutating the expression and the conformation of its constitutive hormones and receptors. We show that trade-off shapes do indeed evolve in this model through the combined action of genetic drift and selection, such that their evolutionarily expected curvature and length depend on context. In particular, a trade-offs shape should depend on the cost associated with the resource storage, itself depending on the traded resource and on the ecological context. Despite this convergence at the phenotypic level, we show that a variety of physiological mechanisms may evolve in similar simulations, suggesting redundancy at the genetic level. This model should provide a useful frame-work to interpret and link the overly complex observations of evolutionary endocrinology and evo-lutionary ecology.

evolutionary biology↗