Research / Scientific departments

Genomes and Genetics Department Activity Report

DIRECTOR : Didier MAZEL

The department gathers 13 scientific groups, and 4 technical platforms. Our current projects deal with the genetics of various living organisms, from bacteria, yeasts and fungi, to human beings. The department has a strong in silico component, with several groups involved in bioinformatics, systems biology and mathematical and physical approaches. Our technical platforms are dealing with genomics applications at large, from sequencing, genome analysis, annotation to expression analysis, and databases development.


EVENTS

Among the different studies carried in the departement one can highlight a few examples:

- The Rocha group used the patterns of genome organization to characterize and infer the patterns of growth in prokaryotes. This allowed for the first time to build a predictor of minimal generation times and to use it to analyse metagenomics data. By these analyses we could test how fundamental ecological theories, e.g. succession theory, applied to the human microbiome after birth and through adult life.

- The Quintana group has observed an enrichment for signals of positive selection (selective advantage) at alleles that are associated with immunity-related phenotypes. Interestingly, in many cases, the positively selected alleles or haplotypes do not confer protection against disease, as expected, but instead increase risk, particularly for autoimmune or inflammatory disorders. This observation opens the possibility that haplotypes that are today associated with increased risk for autoimmune or inflammatory disorders may have conferred increased resistance infectious agents.

A collaborative work led by M. Ricchetti has shown that E. coli strains possess a distinct end-joining activity that repairs double strand breaks and generates genome rearrangements. This mechanism, named alternative end-joining (A-EJ), does not rely on the key non-homologous EJ proteins, which are absent in E. coli, and is characterized by extensive end-resection, by overwhelming usage of microhomology and extremely rare DNA synthesis. This finding demonstrates that E. coli can integrate unrelated, nonhomologous exogenous sequences by end-joining and it provides an alternative strategy for horizontal gene transfer in the bacterial genome.

  • The Mazel group has revealed that the common horzontal gene transfer mechanisms, conjugation and transformation, genrally trigger the SOS response in the recipient bacteria, and thus transiently increase the mutation rates and give higher chance to the recipient bacteria and the mobile genetic elements to co-adapt.

  • The Vergassola group has shown that adaptation observed in the chemotactic bacterial system of E. coli is driven by the need to cope with space-time environmental fluctuations. This should be contrasted with previous explanations qualitatively based on the extension of the dynamic range of response. The strategy of adaptation corresponds to the game-theoretical strategy of minimum risk (MaxiMin), suggesting that chemotaxis is selected in harsh conditions of scarce nutrients and strong fluctuations in the environment. Ongoing experiments are testing the expected loss of adaptation in predictable environments.

  • Using telomeres as a model for the understanding of the mechanisms underlying the physical interactions that govern some genome functions, Emmanuelle Fabre and her collaborators have shown through high throughput 3D microscopy and image analysis in living yeast cells, that interactions between chromosome ends are transient and infrequent. These interactions are rather governed by physical constraints including chromosome structure , attachment to the nuclear envelope and nuclear crowding.

PUBLICATIONS

 

The department published a total of 94 articles in 2010, among which :
 


Barreiro, L. B. & L. Quintana-Murci (2010) From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet 11: 17-30.

Cazalet C, Gomez-Valero L, Rusniok C, Lomma M, Dervins-Ravault D, Newton HJ, Sansom FM, Jarraud S, Zidane N, Ma L, Bouchier C, Etienne J, Hartland EL, Buchrieser C. (2010) Analysis of the Legionella longbeachae genome and transcriptome uncovers unique strategies to cause Legionnaires' disease. PLoS Genet. 6(2):e1000851.

Celani A. & Vergassola M. (2010) Bacterial strategies for chemotaxis response. Proc Natl Acad Sci USA, 107 : 391-1396.

Chayot R, Montagne B, Mazel D and Ricchetti M. (2010) An End-Joining repair mechanism in Escherichia coli. Proc Natl Acad Sci USA, 107:2141-6.
 
Dujon B. (2010) Yeast evolutionary genomics. Nat Rev Genet. 11(7):512-24.

Loot C, Bikard D, Rachlin A and Mazel D. (2010) Cellular pathways controlling integron cassette site folding. EMBO J. 29(15): 2623–34

Rusniok, C., Couve E., Da Cunha V., El Gana R., Zidane N., Bouchier C., Poyart C., Leclercq R., Trieu-Cuot P., and Glaser P. (2010) Genome sequence of Streptococcus gallolyticus: insights into its adaptation to the bovine rumen and its ability to cause endocarditis. Journal of Bacteriology. 192 :2266-2276

Vediyappan, G., Rossignol, T., and d'Enfert, C. (2010) Interaction of Candida albicans biofilms with antifungals: transcriptional response and binding of antifungals to beta-glucans, Antimicrob Agents Chemother 54, 2096-2111.

 

Therizols P, Duong T, Dujon B, Zimmer C, Fabre E. (2010) Chromosome arm length and nuclear constraints determine the dynamic relationship of yeast subtelomeres. Proc Natl Acad Sci USA, 107:2025-30.

Vieira-Silva, S. & E. P. C. Rocha, (2010) The Systemic Imprint of Growth and its Uses in Ecological (Meta) genomics. PLoS Genet 6: e1000808.


PRIZES

Lluis Quintana-Murci was awarded with the Prix Simone & Cino del Duca (Academie des Sciences, Paris), Massimo Vergasola, was awarded with the Prix Thérèse Lebrasseur 2010, Alain Jacquier the prix CEA 2010 de l’Académie des Sciences and Didier Mazel received the Prix Pasteur Vallery-Radot (Paris)