Section: Application Domains
Comparative Genomics of Yeasts
The best way to understand the structure and the evolutionary history of a genome is to compare it with others. At the level of single genes this is a standard and indeed essential procedure: one compares a gene sequence with others in data banks to identify sequence similarities that suggest homology relations. For most gene sequences these relations are the only clues about gene function that are available. The procedure is essential because the difference between the number of genes identified by in silico sequence analysis and the number that are experimentally characterized is several orders of magnitude. At the level of whole genomes, large-scale comparison is still in its infancy but has provided a number of remarkable results that have led to better understanding, on a more global level, of the mechanisms of evolution and of adaptation.
Yeasts provide an ideal subject matter for the study of eukaryotic microorganisms. From an experimental standpoint, the yeast Saccharomyces cerevisiae is a model organism amenable to laboratory use and very widely exploited, resulting in an astonishing array of experimental results.
From a genomic standpoint, yeasts from the hemiascomycete class provide a unique tool for studying eukaryotic genome evolution on a large scale. With their relatively small and compact genomes, yeasts offer a unique opportunity to explore eukaryotic genome evolution by comparative analysis of several species. Yeasts are widely used as cell factories, for the production of beer, wine and bread and more recently of various metabolic products such as vitamins, ethanol, citric acid, lipids, etc. Yeasts can assimilate hydrocarbons (genera Candida , Yarrowia and Debaryomyces ), depolymerise tannin extracts (Zygosaccharomyces rouxii ) and produce hormones and vaccines in industrial quantities through heterologous gene expression. Several yeast species are pathogenic for humans. The most well known yeast in the Hemiascomycete class is S. cerevisiae , widely used as a model organism for molecular genetics and cell biology studies, and as a cell factory. As the most thoroughly-annotated genome of the small eukaryotes, it is a common reference for the annotation of other species. The hemiascomycetous yeasts represent a homogeneous phylogenetic group of eukaryotes with a relatively large diversity at the physiological and ecological levels. Comparative genomic studies within this group have proved very informative [31] , [33] , [45] , [44] , [35] , [47] , [36] .
The Génolevures program is devoted to large-scale comparisons of yeast genomes from various branches of the Hemiascomycete class, with the aim of addressing basic questions of molecular evolution such as the degrees of gene conservation, the identification of species-specific, clade-specific or class-specific genes, the distribution of genes among functional families, the rate of sequence and map divergences and mechanisms of chromosome shuffling.
The differences between genomes can be addressed at two levels: at a molecular level, considering how these differences arise and are maintained; and at a functional level, considering the influence of these molecular differences on cell behavior and more generally on the adaptation of a species to its ecological niche.
