DNA methyltransferases are best known as components of restriction-modification (R-M) systems. These serve as a form of immune response for bacteria against incoming DNA. However, these are also selfish elements acting akin to toxin-antitoxin systems. In addition, there are also solitary methyltransferases, which are not associated with restriction enzymes. These may have core regulatory functions, as best studied for the Dam methylase in E. coli; and / or they may confer protection against parasitism by R-M systems, as demonstrated for the Dcm methylase in E. coli. Here I will talk about a comparative genomics survey investigating the balance between the occurrences of DNA methyltransferases as solitary or R-M systems. I will finally present a discussion on the role of the DNA cytosine methyltransferase in regulating gene expression in E. coli.

L’accumulation de données de séquences chez les procaryotes pose de nombreux défis aux évolutionnistes. Tout d’abord, la prise de conscience, relativement récente, de l’importance fondamentale des transferts horizontaux dans l’évolution des procaryotes fait que l’approche phylogénétique classique, sous la forme d’un arbre des espèces unique, est sans doute un mauvais descripteur de la diversité. Les génomes procaryotes étant mieux décrits comme des mosaïques génétiques, il paraît prometteur de complémenter cette approche classique par l’exploration de méthodes alternatives, comme les forêts d’arbres ou encore les réseaux évolutionnaires. Par ailleurs, ces transferts se font souvent par l’intermédiaire d’éléments génétiques mobiles, comme les plasmides ou les virus, et il est donc essentiel d’inclure ces objets dans l’analyse pour avoir une vision plus complète de l’évolution. Enfin, la quantité considérable de séquences disponibles impose le développement de méthodes d’analyses pragmatiques, aussi rapides que possible. Cette conférence présentera quelques pistes de réponses à ces questions, en particulier…

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