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Escherichia coli represents the major part of commensal aero-anaerobic microbiota of the host’s digestive tract. Though, E. coli is also one of the most frequently encountered species in human and animal pathology. This is one of the most studied and the best known bacterial species. The evolution of genomes within the species is based on two distinct mechanisms: mutation and recombination that generate genetic diversity on which natural selection can operate. In our work, we were interested in those processes and the traces they leave in the genomes. We have at first described a form of variable mutability along the genome which is linked to the existence of local secondary DNA structure: the transcriptional mutability. We were able to quantify this mutagenesis and reveal a selective104response in the genome to limit its effects. Recombination is known to blur the phylogenetic signal significantly. Then, we have shown by a comparative genomics approach that, despite a relatively high recombination rate, the establishment of a robust phylogeny was possible. In addition, we have shown that the many acquisitions and loss of genes occurring in the genomes of different E. coli strains were located preferentially at certain sites. Lastly, we have used the phylogenetic structure of the species to study taxonomic and epidemiologic applications., Escherichia coli constitue la majeure partie de la flore microbienne commensale aéro-anaérobie du tube digestif de l’hôte. Pourtant E. coli est aussi une des espèces les plus fréquemment rencontrées en pathologie humaine et animale. C’est l’une des espèces bactériennes les plus étudiées et les plus connues. L’évolution des génomes au sein de l’espèce repose sur deux mécanismes distincts : la mutation et la recombinaison, qui génèrent une diversité génétique sur laquelle la sélection naturelle peut opérer. Dans notre travail, nous nous sommes intéressés à ces processus et aux traces qu’ils laissent dans les génomes. Nous avons, en premier lieu, décrit une forme de mutabilité variable le long du génome car liée à l‘existence de structure secondaire locale de l’ADN : la mutabilité transcriptionnelle. Nous avons pu d’une part quantifier cette mutagenèse et d’autre part révéler une réponse sélective au sein du génome pour en limiter les effets. La recombinaison, quant à elle, est connue pour brouiller le signal phylogénétique de manière importante. En second lieu, nous avons montré par une approche de génomique comparative que, malgré un taux relativement élevé de recombinaison, l’établissement d’une phylogénie robuste était possible. De plus, nous avons mis en évidence que les nombreuses acquisitions et pertes de gènes dans le génome des différentes souches d’E. coli se situaient préférentiellement à certains sites. Enfin, nous avons utilisé la structure phylogénétique de l’espèce à des applications taxonomiques et épidémiologiques.

Congenital adrenal hyperplasia caused by 21-hydroxylase deficiency is a recessive autosomal genetic disease due to lesion of the gene coding for cytochrome P450c21. Classically, congenital adrenal hyperplasia is divided into two types: one virilizing and called congenital, with or without loss of salt, the other called late onset. In reality, behind this oversimplification lies a clinically, biochemically and genetically heterogeneous disease. Clinical and laboratory findings reflect a continuous impairment of 21-hydroxylase activity. A study of the CYP21B gene located in an important duplicated region of the genome (short arm of chromosome 6, between the HLA-B and -DR loci) where numerous rearrangements take place confirm this heterogeneity. About 25 percent of CYP21B gene lesions are deletions or conversions of a long fragment of the CYP21B gene into the CYP21A pseudogene. The other lesions (75 percent) consist of point mutations that are all present in the CYP21A pseudogene, which suggests microconversion between the two genes. Determining these lesions in the patients provide a better understanding of the clinical heterogeneity and will soon be the basis of the prenatal diagnosis.

Following busulfan induced bone marrow insufficiency, a patient witha chronic granulocytic leukemia (CGL) has had a survival lasting 18.5 years. During remission, chromosome studies on bone marrow have not shown Philadelphia chromosome (Ph 1). There was no correlation between this observation and initial pronostic factors from literature. Analysis of 14 cases (13 from literature) of prolonged survival showed that Ph 1 was absent in 4 cases when only 15% of CGL are initially Ph 1 negative. Therapeuticcaryoconversions were probable. Recently attempts have been made to eradicate the abnormal Ph 1 positive clone. Some hopeful results are reported.