Biology subjects

Meleard, S.

Publications and source records attributed to Meleard, S..

6 recordsLinked to original sources

bioRxiv2025

Classical Myelo-Proliferative Neoplasms emergence and development based on real life incidence and mathematical modeling

Mathematical modelling allows us to better understand the emergence and evolution of myeloproliferative neoplasms. We tested different mathematical models on a first cohort (patients) (Cote dOr Registry) to determine the onset and evolution times before JAK2V617F classical myeloproliferative disorders (polycythemia vera and essential thrombocythemia) are diagnosed. We considered the time to diagnosis as the sum of two periods: the time (from embryonic development) for the JAK2V617F mutation to appear, not disappear and enter proliferation, and a second period corresponding to the expansion of the clonal population until diagnosis. Using increasingly complex models, we show that the rate of active mutation cannot be constant, but rather increases exponentially with age, following the well-known Gompertz model. We found that it takes an average of 63.1 +/- 13 years for the first tumor cell to appear and start proliferating. On the other hand, the expansion time is constant: 8.8 years once the mutation has occurred. These results were validated in an external cohort (national FIMBANK cohort). Using this model, we analyzed JAK2V167F Essential Thrombocythemia versus Polycythemia Vera and found that the time to active mutation in PV is about 1.5 years longer than in ET, while the expansion time is similar. In conclusion, our multi-step approach and the final age-dependent model for the onset and development of MPN shows that the onset of a JAKV617F mutation should be linked to an ageing mechanism and indicates a period of 8-9 years for the development of a full MPN.

cancer biology↗

bioRxiv2022

Drosophilid cuticle pigmentation impacts body temperature

Cuticle pigmentation has been clearly demonstrated to impact body temperature for several relatively large species of insects, but it was questioned for small insects. Here we used a thermal camera to assess the impact of drosophilid cuticle pigmentation on body temperature when individuals are exposed to light. We compared mutants of large effects within species (Drosophila melanogaster ebony and yellow mutants). Then we analyzed the impact of naturally occurring pigmentation variation within species complexes (Drosophila americana/Drosophila novamexicana and Drosophila yakuba/Drosophila santomea). Finally we analyzed lines of D. melanogaster with moderate differences in pigmentation. We found significant differences in temperatures for each of the four pairs we analyzed. The temperature differences appeared to be proportional to the differently pigmented area: between Drosophila melanogaster ebony and yellow mutants or between Drosophila americana and Drosophila novamexicana, for which the whole body is differently pigmented, the difference in temperatures was around 0.6{degrees}C {+/-}0.2{degrees}C. By contrast, between D. yakuba and D. santomea or between Drosophila melanogaster Dark and Pale lines, for which only the posterior abdomen is differentially pigmented, we detected a temperature difference of about 0.14{degrees}C {+/-}0.10{degrees}C. This demonstrates that cuticle pigmentation has ecological implications in drosophilids regarding adaptation to environmental temperature.

evolutionary biology↗

bioRxiv2022

Human-environment feedback and the consistency of proenvironmental behaviour

Addressing global environmental crises such as anthropogenic climate change requires the consistent adoption of proenvironmental behavior by a large part of a population. Here, we develop a mathematical model of a simple behavior-environment feedback loop to ask how the individual assessment of the environmental state combines with social interactions to influence the consistent adoption of proenvironmental behavior, and how this feeds back to the perceived environmental state. In this stochastic individual-based model, individuals can switch between two behaviors, active (or actively proenvironmental) and baseline, differing in their perceived cost (higher for the active behavior) and environmental impact (lower for the active behavior). We show that the deterministic dynamics and the stochastic fluctuations of the system can be approximated by ordinary differential equations and a Ornstein-Uhlenbeck type process. By definition, the proenvironmental behavior is adopted consistently when, at population stationary state, its frequency is high and random fluctuations in frequency are small. We find that the combination of social and environmental feedbacks can promote the spread of costly proenvironmental behavior when neither, operating in isolation, would. To be adopted consistently, strong social pressure for proenvironmental action is necessary but not sufficient - social interactions must occur on a faster timescale compared to individual assessment, and the difference in perceived environmental impact must be small. This simple model suggests a scenario to achieve large reductions in environmental impact, which involves incrementally more active and potentially more costly behavior being consistently adopted under increasing social pressure for proenvironmentalism.

ecology↗

bioRxiv2022

Positive selection of senescence through increased evolvability: ageing is not a by-product of evolution.

Signs of ageing become apparent only late in life, after organismal development is finalized. Ageing, most notably, decreases an individuals fitness. As such, it is most commonly perceived as a non-adaptive force of evolution and considered a by-product of natural selection. Building upon the evolutionarily conserved age-related Smurf phenotype, we propose a simple mathematical life-history trait model in which an organism is characterized by two core abilities: reproduction and homeostasis. Through the simulation of this model, we observe 1) the convergence of fertilitys end with the onset of senescence, 2) the relative success of ageing populations, as compared to non-ageing populations, and 3) the enhanced evolvability (i.e. the generation of genetic variability) of ageing populations. In addition, we formally demonstrate the mathematical convergence observed in 1). We thus theorize that mechanisms that link the timing of fertility and ageing have been selected and fixed over evolutionary history, which, in turn, explains why ageing populations are more evolvable and therefore more successful. Broadly speaking, our work suggests that ageing is an adaptive force of evolution.

evolutionary biology↗

bioRxiv2021

Viral transduction and the dynamics of bacterial adaptation

Transduction - horizontal gene transfer (HGT) by viruses - is an important macroevolutionary force in prokaryotes, contributing to functional innovation and lineage diversification. In contrast, the role that transduction plays in bacterial microevolutionary adaptation is poorly known. By facilitating the transfer of beneficial alleles between host cells, transduction may accelerate adaptation. But transduction also carries the risk of transferring deleterious alleles, which, in addition to the demographic cost of viral infection, may hinder adaptation. Here we resolve the conflicting effects of transduction on bacterial adaptation in a simple eco-evolutionary model for large populations characterized by a quantitative (resource-use) trait with a single evolutionary optimum. Our model focuses on generalized transduction by virulent phages. Away from the optimum, the effect of transferring beneficial alleles dominates and transduction tends to accelerate adaptation. Close to the optimum, transduction generates a large amount of stochasticity in the population adaptive trajectory, thus hindering adaptation. Under disruptive selection, transduction may either limit (as sexual recombination would) or promote phenotypic diversification, or drive transient optimization whereby phenotypic subpopulations recurrently visit the optimum. Our modeling framework paves the way to study complex adaptive feedbacks between bacterial hosts and phages generated by the combination of deterministic and stochastic effects of transduction.

evolutionary biology↗

bioRxiv2019

Inference with selection, varying population size and evolving population structure: Application of ABC to a forward-backward coalescent process with interactions

Genetic data are often used to infer history, demographic changes or detect genes under selection. Inferential methods are commonly based on models making various strong assumptions: demography and population structures are supposed a priori known, the evolution of the genetic composition of a population does not affect demography nor population structure, and there is no selection nor interaction between and within genetic strains. In this paper, we present a stochastic birth-death model with competitive interaction to describe an asexual population, and we develop an inferential procedure for ecological, demographic and genetic parameters. We first show how genetic diversity and genealogies are related to birth and death rates, and to how individuals compete within and between strains. This leads us to propose an original model of phylogenies, with trait structure and interactions, that allows multiple merging. Second, we develop an Approximate Bayesian Computation framework to use our model for analyzing genetic data. We apply our procedure to simulated and real data. We show that the procedure give accurate estimate of the parameters of the model. We finally carry an illustration on real data and analyze the genetic diversity of microsatellites on Y-chromosomes sampled from Central Asia populations in order to test whether different social organizations show significantly different fertility.

genetics↗