Biology subjects

de Vienne, D.

Publications and source records attributed to de Vienne, D..

8 recordsLinked to original sources

bioRxiv2025

Propagation of genotypic variation across phenotypic levels: a model based on concave relationships unifies disparate observations on phenotypic buffering, dominance, heritability, and inbreeding depression

The way genetic variation propagates across successive phenotypic levels up to the fitness components is central to the issue of the genotype-phenotype relationship. The processes involved are highly non-linear, and exhibit a large diversity of behaviors depending on the genes, organization levels, and traits considered. Nevertheless, the shape of the relationship between traits from adjacent levels is predominantly concave, which is probably due to global constraints on matter and energy in the cell. Based on this observation, we used the properties of concave functions to model how phenotypic differences and inheritance vary across increasingly integrated levels of organization. We show that the more integrated the phenotypic levels, the closer the phenotypic values and the larger the positive deviation from additivity (i.e. dominance or heterosis). These results may explain various observations such as the low heritability and high inbreeding depression of fitness components, and the phenotypic buffering of molecular polymorphisms. Furthermore, the introduction of a cost/crowding factor in the model may explain why overdominance is so rare while heterosis is so common. To our knowledge, this systems biology approach to the genotype-phenotype relationship is the first to be based on a theoretical model of the propagation of genetic variation across phenotypic levels.

genetics↗

bioRxiv2021

Evolution of enzyme levels in metabolic pathways: A theoretical approach. Part 2

Metabolism is essential for cell function and adaptation. Because of their central role in metabolism, kinetic parameters and enzyme concentrations are under constant selective pressure to adapt the fluxes of the metabolic networks to the needs of the organism. In the line of various studies dealing with enzyme evolution, we recently developed a model of evolution of enzyme concentrations under selection for increased flux, considered as a proxy of fitness (Coton et al. 2021). Taking into account two realistic cellular constraints, competition for resources and co-regulations, we determined the evolutionary equilibria and the ranges of neutral variations of enzyme concentrations. In this article, we give more generality to this model, by considering that the enzymes of a pathway can belong to different groups of co-regulation. We determined the equilibria and showed that the constraints modify the adaptive landscape by limiting the number of independent dimensions. We also showed that any trade-off between enzyme concentration is sufficient to limit the flux and to relax selection for increasing other enzyme concentrations. Even though the model is based on simplifying assumptions, the complexity of the relationship between enzyme concentrations prevents the analysis of selective neutrality.

evolutionary biology↗

bioRxiv2021

Evolution of enzyme levels in metabolic pathways: A theoretical approach

The central role of metabolism in cell functioning and adaptation has given rise to count-less studies on the evolution of enzyme-coding genes and network topology. However, very few studies have addressed the question of how enzyme concentrations change in response to positive selective pressure on the flux, considered a proxy of fitness. In particular, the way cellular constraints, such as resource limitations and co-regulation, affect the adaptive landscape of a pathway under selection has never been analyzed theoretically. To fill this gap, we developed a model of the evolution of enzyme concentrations that combines metabolic control theory and an adaptive dynamics approach, and integrates possible dependencies between enzyme concentrations. We determined the evolutionary equilibria of enzyme concentrations and their range of neutral variation, and showed that they differ with the properties of the enzymes, the constraints applied to the system and the initial enzyme concentrations. Simulations of long-term evolution confirmed all analytical and numerical predictions, even though we relaxed the simplifying assumptions used in the analytical treatment.

evolutionary biology↗

bioRxiv2020

Data integration uncovers the metabolic bases of phenotypic variation in yeast

The relationship between different levels of integration is a key feature for understanding the genotype-phenotype map.Here, we describe a novel method of integrated data analysis that incorporates protein abundance data into constraint-based modeling to elucidate the biological mechanisms underlying phenotypic variation. Specifically, we studied yeast genetic diversity at three levels of phenotypic complexity in a population of yeast obtained by pairwise crosses of eleven strains belonging to two species, Saccha-romyces cerevisiae and S. uvarum. The data included protein abundances, integrated traits (life-history/fermentation) and computational estimates of metabolic fluxes.Results highlighted that the negative correlation between production traits such as population carrying capacity (K) and traits associated with growth and fermentation rates (Jmax) is explained by a differential usage of energy production pathways: a high K was associated with high TCA fluxes, while a high Jmax was associated with high glycolytic fluxes. Enrichment analysis of protein sets confirmed our results.This powerful approach allowed us to identify the molecular and metabolic bases of integrated trait variation, and therefore has a broad applicability domain.View Full Text

systems biology↗

bioRxiv2019

Heterosis indices: What do we really measure?

Heterosis (hybrid vigour) is a universal phenomenon of crucial agro-economic and evolutionary importance. We show that the most common heterosis indices do not properly measure deviation from additivity because they include both a component accounting for "real" heterosis and a term that is not related to heterosis since it is derived solely from parental values. Therefore, these indices are inadequate when the aim of the study is to compare heterosis levels between different traits, environments, genetic backgrounds or developmental stages, as these factors may affect not only heterosis but also parental values. The only relevant index for such comparisons is the so-called "potence ratio". These observations argue for the careful choice of heterosis indices depending on the purpose of the work. HighlightUnlike dominance indices, heterosis indices, with one exception, do not properly measure the level of deviation from additivity, thus making them unsuitable for comparative analyses.

genetics↗

bioRxiv2018

Non-linear phenotypic variation uncovers the emergence of heterosis in Arabidopsis thaliana

Heterosis describes the phenotypic superiority of hybrids over their parents in traits related to fitness. Understanding and predicting non-additive inheritance such as heterosis is crucial for evolutionary biology, as well as for plant and animal breeding. However, the physiological bases of heterosis remain debated. Moreover, empirical data in various species have shown that diverse genetic and molecular mechanisms are likely to explain heterosis, making it difficult to predict its emergence and amplitude from parental genotypes alone. In this study, we evaluated a model of physiological dominance proposed by Sewall Wright to explain the non-additive inheritance of metabolic fluxes at the cellular level. We used 450 hybrids derived from crosses among natural inbred accessions of Arabidopsis thaliana to test Wrights model for two fitness-related traits at the whole-plant level: growth rate and fruit number. We found that allometric relationships between traits constrain phenotypic variation in hybrids and inbreds to a similar extent. These allometric relationships behave predictably, in a non-linear manner, explaining up to 75% of heterosis amplitude, while genetic distance among parents at best explains 7%. Thus, our findings are consistent with Wrights model of physiological dominance on plant performance, and suggest that the emergence of heterosis is an intrinsic property of non-linear relationships between traits. Furthermore, our study highlights the potential of a geometric approach of phenotypic relationships for predicting heterosis of two major components of crop productivity and yield.

evolutionary biology↗

bioRxiv2018

Decoupling of heterosis and inbreeding variances is evidenced in yeast’s life-history and proteomic traits

Heterosis (hybrid vigor) and inbreeding depression, commonly considered as corollary phenomena, could nevertheless be decoupled under certain assumptions according to theoretical population genetics works. In order to explore this issue on real data, we analyzed the components of genetic variation in a population derived from a half-diallel cross between strains from Saccharomyces cerevisiae and S. uvarum, two related yeast species involved in alcoholic fermentation. A large number of phenotypic traits, either molecular (coming from quantitative proteomics) or related to fermentation and life-history, were measured during alcoholic fermentation. Because the parental strains were included in the design, we were able to distinguish between inbreeding effects, which measures phenotypic differences between inbred and hybrids, and heterosis, which measures phenotypic differences between a specific hybrid and the other hybrids sharing a common parent. The sources of phenotypic variation differed depending on the temperature, indicating the predominance of genotype by environment interactions. Decomposing the total genetic variance into variances of additive (intra- and inter-specific) effects, of inbreeding effects and of heterosis (intra- and inter-specific) effects, we showed that the distribution of variance components defined clear-cut groups of proteins and traits. Moreover, it was possible to cluster fermentation and life-history traits into most proteomic groups. Within groups, we observed positive, negative or null correlations between the variances of heterosis and inbreeding effects. To our knowledge, such a decoupling had never been experimentally demonstrated. This result suggests that, despite a common evolutionary history of individuals within a species, the different types of traits have been subject to different selective pressures.

systems biology↗

bioRxiv2017

The geometry of heterosis

Heterosis, the superiority of hybrids over their parents for quantitative traits, represents a crucial issue in plant and animal breeding. Heterosis has given rise to countless genetic, genomic and molecular studies, but has rarely been investigated from the point of view of systems biology. We hypothesized that heterosis is an emergent property of living systems resulting from frequent concave relationships between genotypic variables and phenotypes, or between different phenotypic levels. We chose the enzyme-flux relationship as a model of the concave genotype-phenotype (GP) relationship, and showed that heterosis can be easily created in the laboratory. First, we reconstituted in vitro the upper part of glycolysis. We simulated genetic variability of enzyme activity by varying enzyme concentrations in test tubes. Mixing the content of \"parental\" tubes resulted in \"hybrids\", whose fluxes were compared to the parental fluxes. Frequent heterotic fluxes were observed, under conditions that were determined analytically and confirmed by computer simulation. Second, to test this model in a more realistic situation, we modeled the glycolysis/fermentation network in yeast by considering one input flux, glucose, and two output fluxes, glycerol and acetaldehyde. We simulated genetic variability by randomly drawing parental enzyme concentrations under various conditions, and computed the parental and hybrid fluxes using a system of differential equations. Again we found that a majority of hybrids exhibited positive heterosis for metabolic fluxes. Cases of negative heterosis were due to local convexity between certain enzyme concentrations and fluxes. In both approaches, heterosis was maximized when the parents were phenotypically close and when the distributions of parental enzyme concentrations were contrasted and constrained. These conclusions are not restricted to metabolic systems: they only depend on the concavity of the GP relationship, which is commonly observed at various levels of the phenotypic hierarchy, and could account for the pervasiveness of heterosis.

systems biology↗