The size of genomes exhibits a great variability despite a relatively similar number of protein coding genes. The increase in metazoan genomes sizes is partly due to the multiplication of repetitive DNA sequences. Despite their abundance, the role of these sequences remains largely unknown. It has been proposed that they might organize the 3D folding of genomes in nuclei and therefore play a role in the regulation of gene expression. To test this hypothesis we combined the most recent genome-wide Chromosomal Conformation Capture data together with genome annotations for the repetitive DNA sequences. We show that in human, mouse and drosophila, the genome is organized in a way that enables the specific co-localization of similar DNA repeats; few of which were already known to bridge distant parts of the genome. We finally show that the 3D organization of synteny blocs in mammalian nuclei is conserved in human and mouse. We propose that…

Recognition of pathogens relies on the diversity of immune receptor proteins. Recent experiments that sequence the entire immune cell repertoires provide a new opportunity for quantitative insight into naturally occurring diversity and how it is generated. The generation process is implemented via a series of stochastic molecular events involving gene choices and random nucleotide insertions between, and deletions from, genes. I will describe how we can attempt to quantify the diversity of the receptors formed in this complex process and point to the origins of diversity in these sequences

Cells live in contexts with limited resources, and evolution has selected mechanisms that allow them to accomplish the tasks essential for life by making optimal use of the resources. This idea spans from one extreme of complexity of the cellular world (bacteria) to another (cancer cells), and is, in essence, the basis of constraint-based modeling, possibly the most successful approach for unraveling cell energetics. More or less recent work aimed at correlating energetics with thermodynamic and regulatory properties has brought to light a number of facts that are not explained by current theories. To make progress and understand whether evolution has found optimal solutions requires us to dig deeper into the space of possible states of a cell's metabolic network, and into the nature of the constraints that define it. We shall see how important hints derived from thermodynamical and regulatory considerations lead to novel insights and (possibly) entirely new classes of…

Au sein de la grande diversité des modèles en Neurosciences Computationnelles, l’approche biophysique permet d’évaluer la manière dont les propriétés neuronales locales (excitabilité, transmission synaptique, règles de plasticité) participent à l’émergence de propriétés d’intérêt à l’échelle globale des réseaux de neurones (traitement de l’information, apprentissage, mémoire, organisation du comportement). Ces modèles reposent sur 1) un travail d’extraction des propriétés moléculaires et cellulaires pertinentes (bibliographie approfondie, collaboration avec les expérimentateurs), 2) la construction et la réduction de dimensionnalité – attentives – de modèles locaux réalistes résumant ces propriétés, 3) l’incorporation de celles–ci dans des modèles de réseaux de neurones, et l’étude de leur expression dans les propriétés émergentes observées. En filigrane, une notion récurrente dans cette approche matérialiste et déterministe est la dynamique des systèmes neuronaux étudiés, c’est à dire leur neurodynamique. Cette notion est importante car elle permet de prendre en compte l’interaction entre les informations externes et l’état interne de l’individu.…

Adaptation proceeds through the selection of mutations. The distribution of mutant fitness effect and the forces shaping this distribution are therefore keys to predict the evolutionary fate of organisms and their constituents such as enzymes. Here, by producing and sequencing a comprehensive collection of 10,000 mutants, we explore the mutational landscape of one enzyme involved in the spread of antibiotic resistance, the beta-lactamase TEM-1. We measured mutation impact on the enzyme activity through the estimation of amoxicillin Minimum Inhibitory Concentration (MIC) on a subset of 990 mutants carrying a unique missense mutation, representing 64% of possible amino acid changes in that protein reachable by point mutation. We established that mutation type, solvent accessibility of residues and the predicted effect of mutations on protein stability primarily determined alone or in combination changes in MIC of mutants. Moreover, we were able to capture the drastic modification of the mutational landscape induced by a single…

Dozens of genes are known to control the pathways of crossover formation between homologs during meiosis. In most species, crossovers interfere, a phenomenon first discovered in the Morgan lab nearly a century ago. Nevertheless the mechanisms producing crossover interference remain unknown. I will show how quantitative modeling has been used, what has been learned, and the road still ahead.

Microbes engage in a remarkable array of cooperative behaviors, secreting shared proteins that are essential for foraging, shelter, microbial warfare and virulence. These proteins are costly, rendering populations of cooperators vulnerable to exploitation by non-producing cheaters arising by gene loss or migration. In such conditions, how can cooperation persist? Our model predicts that more mobile loci generate higher relatedness, and therefore allow the maintenance of more cooperative traits via kin selection. By analyzing bacterial genomes we observe a massive amount of horizontal transfer and show that this is the predominant mechanism of innovation in bacterial genomes. Additionally, this shows that we are far from knowing the diversity of functions encoded in the species. We confirm that genes coding for secreted proteins - the secretome – are very frequently lost and gained and are associated with mobile elements, supporting our major prediction that gene mobility drives bacterial cooperation. We demonstrate that mobile elements…