How do genes arise ? Lessons and questions from the evolution of yeast genomes. – GENARISE

Fundamental questions about the molecular mechanisms that underlie the evolution of eukaryotic organisms can now be addressed with a previously unknown degree of precision and comprehensiveness thanks to the rapidly expanding number of complete genome sequences. Comparisons between distinct organisms from a same phylum help us disentangle the distorted and superimposed traces left in genomes by the successive, numerous evolutionary events. But the pictures obtained are clearer when some of the compared organisms are also amenable to experimentation, as is the case for hemiascomycete yeasts. This project focuses on original aspects of eukaryotic genome evolution, suggested by several recent comparative genomic analyses performed on a variety of eukaryotic organisms including our own efforts on yeasts (see ref. below). Against the background of observed, or experimentally demonstrated mechanisms which contribute to our understanding of evolutionary dynamics, a number of other phenomena requires additional analysis or even raise some unexplained paradoxes. Recent comparative genomic analyses of several yeast species, combined with experiments with Saccharomyces cerevisiae, reveal that yeasts have evolved through a remarkable interplay between distinct molecular mechanisms leading to the formation of novel genes and the loss of others. The advantages of yeast to explore the basic molecular and genetic mechanisms underlying eukaryotic genome evolution are numerous. After the pioneering genome sequence of S. cerevisiae nearly ten years ago (Goffeau et al., 1996), considerable efforts have been placed on global functional analysis, making this model organism a test case for many of the innovative developments in this field (transcriptome, proteome, interactome analysis, protein complexes, synthetic phenotypes, regulatory networks, global replication or recombination maps, systematic protein structure determination, etc..). Beside the technical innovations underlying such remarkable progress, the existence of a complete collection of mutants (a unique case so far in eukaryotes) has considerably accelerated research activities on S. cerevisiae. But in parallel to these exciting developments, comparative genomics has gained considerable momentum during the last years and has revealed a largely unexpected image of the world of yeasts and other eukaryotes, including of course man and other vertebrates. A few years ago, we have initiated the first serious molecular exploration of the genomic diversity of Hemiascomycete yeasts by low coverage sequencing of a selected set of thirteen species (Souciet et al., 2000 and cbi.labri.fr/Genolevures). Since then, this exploration has been largely extended by ourselves (Dujon et al., 2004) and others (Wood et al., 2002, Cliften et al., 2003, Kellis et al., 2003, 2004,.Dietrich et al., 2004, Jones et al., 2004). Altogether, the genomes of over a dozen of hemiascomycete species have now been studied by either complete sequencing or partial random coverages (http://cbi.labri.fr/Genolevures; mips.gsf.de/genre/proj/yeast/index.jsp; www.yeastgenome.org/). With the addition of the genomes from other subclasses of Ascomycetes, such as several filamentous fungi (Euascomycetes) and Schizosaccharomyces pombe (Archiascomyetes), this group of organisms represents the most complete one among eukaryotes for genomic studies, and the sequencing of other groups of fungi is rapidly progressing. One of our surprises with the genomes of the Hemiascomycete yeasts, came from their very large evolutionary range, much larger than traditionally expected for a group of unicellular organisms with similar lifestyles and morphologies. Orthologous protein sequences are more diverged between the two closest yeasts that we have examined (S. cerevisiae and C. glabrata) than between man and the two sequenced fish species (Dujon et al., 2004, Jaillon et al., 2004). A similar conclusion can be drawn from the co.