The Unité has a long-standing interest on the molecular and cellular mechanisms responsible for the functional organization, maintenance, fluidity and evolution of eukaryotic genomes using yeasts as models. It is one of the founding members of the Génolevures Consortium (GDR2354 CNRS) that, in collaboration with Génoscope and the Génopole Pasteur-Ile de France, contributed to major aspects of yeast evolutionary genomics over the last decade. The Unité combines experimental approaches, applied on Saccharomyces cerevisiae and a few other yeast species, with comparative and in-silicoanalyses of genomes of yeasts and other organisms. It holds the complete collection of null-gene mutants of S. cerevisiae.

Comparative genomics and yeast genome evolution:

The Génolevures Consortium has sequenced and annotated nine yeast species (http://www.genolevures.org) representative of the very broad evolutionary range of Saccharomycotinaand including the human pathogen Candida glabrata. It is now further engaged in the exploration of additional yeast genomes to identify novel genome architectures and, hopefully, reveal new important evolutionary transitions. Comparisons of genes or their products as well as of chromosomal organization and synteny between many yeast species revealed important evolutionary features. A clade-specific large expansion of mitochondrial DNA, a chromosome-specific compositional heterogeneity, a naturally-formed hybrid in the process of spontaneous homozygotization, the presence of megasatellites in C. glabrata, the abundance of NUMTsin Debaryomyces hansenii,or novel cases of horizontal gene transfers illustrate the variety of processes operating during yeast genome evolution.

Mechanisms of eukaryotic genome fluidity:

A novel, replication-based mechanism was identified in S. cerevisiaeas responsible for the spontaneous formation of large segmental duplications, similar to those observed in the human genome. Evolution experiments after replacement of essential genes by their orthologs from very distantly related yeasts revealed the importance of this mechanism and illustrated the diversity of the intermediary structures formed. The role of chromosome breaks, recombination and DNA helicases in the stability of triplet-repeats was determined using S. cerevisiaemutants.

Chromosome dynamics and nuclear architecture:

The spatial distribution of subtelomeres around the nuclear periphery was measured quantitatively by fluorescence microscopy of living-cells in wild-type and mutant strains of S. cerevisiae, showing the importance of chromosome arm length, centromere attachment to the spindle pole body, nucleolar volume and nucleopore integrity, as well as the highly dynamic spatial movements of chromosome segments within the nucleus. Novel molecular technologies are now applied on synchronized cells to determine physical interactions between chromosomal segments within the nuclear volume.

Miria Ricchetti Report

Keywords: molecular evolution, genome sequence annotation, new generation sequencing, bioinformatics, genetics, microbial population, cellular structure

A. KERREST, R. ANAND, R. SUNDARARAJAN, R. BERMEJO, G. LIBERI, B. DUJON, C. FREUDENREICH, G-F. RICHARD. (2009) SRS2and SGS1prevent chromosomal breaks and stabilize triplet repeats by restraining recombination. Nature Struct. & Mol. Biol. 16: 159-167.

J-L. Souciet, B. Dujon, C. Gaillardin, M. Johnston, P. V. Baret, P. Cliften, D. J. Sherman, J. Weissenbach, E. Westhof, P. Wincker, C. Jubin, J. Poulain, V. Barbe, B. Segurence, F. Artiguenave, V. Anthouard, B. Vacherie, M. E. Val, R. S. Fulton, P. Minx, R. Wilson, P. Durrens, G. Jean, C. Marck, T. Martin, M. Nikolski, T. Rolland, M-L. Seret, S. Casaregola, L. Despons, C. Fairhead, G. Fischer, I. Lafontaine, V. Leh, M. Lemaire, J. de Montigny, C. Neuveglise, A. Thierry, I. Blanc-Lenfle, C. Bleykasten, J. Diffels, E. Fritsch, L. Frangeul, A. Goeffon, N. Jauniaux, R. Kachouri-Lafond, C. Payen, S. Potier, L. Pribylova, C. Ozanne, G-F. Richard, C. Sacerdot, M-L. Straub, E. Talla. (2009) Comparative genomics of protoploid Saccharomycetaceae. Genome Res.19: 1696-1709.

B. DUJON. Yeast evolutionary genomics. (2010) Nature Rev. Genetics 11: 512-524.

T. ROLLAND, B. DUJON, G-F. RICHARD.(2010) Dynamic evolution of megastellites in yeasts. Nuc. Acids Res. 38: 4731-4739.

P. THERIZOLS, T. DUONG, B. DUJON, C. ZIMMER, E. FABRE. Chromosome arm length and nuclear constraints determine the dynamic relationship of yeastsubtelomeres. (2010) Proc. Natl. Acad. Sc. USA 107: 2025-2030.