The Horizontal Gene Transfer (HGT) debate is about the role played by this mode of gene inheritance in evolution of Life. HGT in prokaryotes may be one reason why species trees built on the basis of different sets of molecular characters are different - the conundrum dubbed “the tree of one percent” after the observation that the consensus ribosomal RNA-based phylogeny of prokaryotes is in fact supported by only a percent of all trees built on the basis of other, protein-coding sequences. I will present the empirical data on gene content and protein sequence evolution in bacteriophages with double-strand DNA genomes. I show that the distributions of genomes and of protein families by the number of HGT events they have experienced have one fat tail and one long tail, i.e., even though the absolute number of inferred HGT events in phage world is high, the frequency of such events in the majority…

Minimal bacterial gene set comprises the genetic elements needed for survival of engineered bacterium on a rich medium. This set is estimated to include 300-350 protein-coding genes. One way of simplifying an organism with such a minimal genome even further is to constrain the amino acid content of its proteins. We used comparative genomics to examine the challenges of completely replacing the two rarest residues, cysteine and tryptophan. Drastic reduction of the content of these amino acids appears to be possible, but their complete elimination is challenging. In particular, cysteine residues in four proteins involved in ribonucleoside modifications appear to be essential, as no alternative chemistry is known for these functions

Sequence comparison has been central to computational biology for many decades, and still is today. Modern tasks include: comparing whole genomes; aligning bisulfite-converted DNA reads to a genome; aligning long, high-error sequences from single molecule sequencers; aligning ancient or degraded DNA; comparing metagenomic DNA to a protein database. Our main argument will be that classic alignment techniques, with substitution score matrices and statistical models, can and should be used for modern data. We will describe how to incorporate sequence quality data, and how to make the seed-and-extend method scale to large datasets by using "adaptive seeds". Finally, we build on the classic statistical model to accurately align paired sequences, and sequences that come from disjoint genomic loci due to rearrangements

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.…