G-quadruplexes (G4) are four stranded nucleic acid secondary structures that form in vitro and in vivo in certain guanine rich sequences, upon stable non-Watson-Crick pairing of four guanines and stacking. G4 biological functions remain elusive, as it is difficult to identify the physiological and molecular circumstances of their formation, stabilization, recognition and processing. Inherently, biological processes generating single-stranded nucleic acids are favourable circumstances. Here, we questioned G4 formation during replication in the yeast S. cerevisiae and describe its pathological consequences. For this, we inserted the G-quadruplex-forming CEB1 minisatellite sequence near the strong and early firing origin ARS305 in both orientations and monitored its behaviour. We show that CEB1 tandem repeats are tolerated in wild-type cells but are very frequently destabilized upon treatment with the PhenDC3 G4-ligand and in the specific absence of the Pif1 unwinding helicase activity but in a preferential orientation manner, namely when the G-rich strand is template of leading…

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A survey of genome wide sequence differences and comprehensive phenotypic differences of many isolates of Saccharomyces cerevisiae and S. paradoxus revealed an apparent paradox of low phenotypic diversity in S. paradoxus while having great genotypic diversity while the opposite is seen in S. cerevisiae. This paradox may be resolved by the understanding of adaptation of populations to their environments where complex traits are composed of linked antagonistic QTLs which can be broken up to reveal phenotypic diversity due to genetic interactions arising from outbreeding. An initial testable model will be described that may account for various observations.

Divergence in gene regulation can play a major role in evolution. I will discuss our phylogenetic framework to measure mRNA profiles in 15 yeast species from the phylum Ascomycota and reconstruct the evolution of their modular regulatory programs along a time course of growth on glucose over 300 million years. We found that modules have diverged proportionally to phylogenetic distance, with prominent changes in gene regulation accompanying changes in lifestyle and ploidy, especially in carbon metabolism. Gene duplication events significantly contribute to regulatory divergence, in particular close to their phylogenetic point of duplication. Paralogs from a whole genome duplication (WGD) event have a uniquely substantial contribution that extends over a longer span. Similar patterns occur when considering the evolution of the heat shock regulatory program measured in eight of the species, suggesting that these are general evolutionary principles.

Among the signals that control the epigenetic landscape, non-coding (nc)RNAs have been identified to play a major role but the generalization and the mechanisms of their activity are still poorly apprehended. Recent data using high-throughput technologies have profoundly changed our view on how the genomes are organized. Indeed transcriptome analyses have shown that large genomic regions are pervasively transcribed producing a broad variety of ncRNA which functions on the epigenome remain to be deciphered. Our recent works show that S. cerevisiae’s genome also supports production of non-coding protein large transcripts, which are strongly controlled by RNA decay pathways. Of specific interest are the lncRNA XUT that we described recently, mostly antisense to class II genes and associated with a consistent regulatory potential through epigenetic modifications. Interestingly, histone methyl transferase and histone deacetylase show strong interplays with large antisense ncRNA. Mechanistic insights of their regulatory activities will be presented and generalization of their…

Vibrios are bacteria responsible for a significant proportion of infections affecting marine invertebrates and represent the major cause of mortality in farmed marine species. They are able to colonize many habitats, exist in free-living planktonic seawater, adhered to surfaces within biofilms or associated with various marine hosts. This high adaptability is linked to their capacity to generate high-levels of genetic diversity, a significant proportion via lateral gene transfer (LGT). LGT is being increasingly recognized as a major driving force in the evolution of virulence traits in vibrio. In contrast to species that are pathogenic to humans little data is available regarding invertebrate pathogens. Recent advances in genomics alongside the domestication of marine invertebrates has provided an opportunity to close the gap in our understanding of vibrio pathogens infecting invertebrates, leading to new and original scientific questions.

The Nakaseomyces clade includes Candida glabrata, a major fungal pathogen of immuno-compromised patients, and five other species, two of which have recently also been identified as human opportunistic pathogens. The genome of C. glabrata was published in 2004, and we have recently sequenced the genomes of all other known species of the Nakaseomyces genus. This clade is much closer to Saccharomyces cerevisiae than to the major Candida clade that includes C. albicans. Indeed, the Nakaseomyces derive from the same ancestor as S. cerevisiae that underwent a whole-genome duplication event, and their genomes contain the elements needed for mating-type switching in S. cerevisiae. These consist of mating-type cassettes of both types in haploid genomes, and the HO gene, that encodes the endonuclease initiating the switching event. Nonetheless, the four “Candida” species within the clade have been described as asexual, and no mating-type switching has been directly observed in any species. All Nakaseomyces seem…